A little below the belt July 2020 by ANZUP Cancer Trials Group

A little below the belt

Making a difference to the lives of people affected by below the belt (bladder, kidney, testicular, penile and prostate) cancers.

AN ANZUP CANCER TRIALS GROUP PUBLICATION

ISSUE 13, JULY 2020

SAVE THE Registrations open DATE 11-30 - 30 September SEPTEMBER 2020 2020

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What is ANZUP? The Australian and New Zealand Urogenital and Prostate Cancer Trials Group was formed in 2008, bringing together a world-leading multidisciplinary team of doctors, nurses, other health care professionals, scientists, researchers, and community representatives, all working in areas related to urogenital cancer.

ANZUP has members in every state and territory in Australia and New Zealand, with an increasing international membership. Urogenital cancers are those coming from the testicles, prostate, kidney, penis or bladder.

ANZUP aims to improve outcomes for people affected by these cancers. We do this by performing clinical trials to generate new evidence for better treatments, or ways of providing other support. Our members and investigators are widely dispersed and busy, working in a range of disciplines. A trial idea only comes to fruition when we are able to provide opportunities for people to meet, work through the science, develop the trial concepts, and write and work through all the other documentation and processes. Then it is necessary to initiate, run, monitor and report the trial results. All of this relies on the volunteered time of our members and is separate from the other needs ANZUP has to source the much larger amounts of funding to support the trials themselves.

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ss and help fund future clinical trials for belo ANZUP acknowledges the Traditional Owners of the lands on which our company is located and where we conduct our business.

ED We IN FINDING OUT MORE pay our respects to ancestors and Elders, past and present. ANZUP is committed to honouring the First Peoples’ unique cultural and spiritual relationships to the land, waters and seas and their rich contribution to society.

UR INTEREST HERE.

The paper used in this edition is called Maine Recycled Digital – Silk. It is made with fibre derived only from sustainable sources and produced with a low reliance on energy from fossil fuels. The purchase of carbon offsets compensates for emissions produced over an international supply chain, from seedling through to final delivery to the customer.

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A LITTLE BELOW THE BELT 3

What’s inside 05 Message from the Chair, Professor Ian Davis 07 CEO Update 09 Our thanks to Associate Professor Guy Toner 11 Consumer Advisory Panel update 12 Friends of ANZUP 14 The importance of clinical trials and research 16 Telehealth and teletrials 18 Finding calm in the face of cancer 19 Out with Cancer study shining a light on LGBTQI+ experiences of cancer 20 New research bridges bench to bedside 21 Spotlight on prostate cancer 23 New class of targeted radioactive treatment effective for men with metastatic prostate cancer 25 New era in nuclear medicine 27 DASL-HiCaP trial led by ANZUP now open

ANZUP Cancer Trials Group Limited Registered office Level 6 Lifehouse Building 119-143 Missenden Road Camperdown NSW 2050 T: +61 2 9562 5042 F: +61 2 9562 5008 www.anzup.org.au @ANZUPtrials / @BelowTheBeltANZ ANZUPtrials / BelowTheBeltCancer ANZUP @ANZUPtrials

29 ANZUP’s ENZAMET trial results recognised as one of the most important clinical research advances of the past year 30 ANZUP trials – prostate 34 Spotlight on bladder and urothelial cancer 36 Patient power – Melissa Le Mesurier 38 ANZUP trials – bladder 41 Spotlight on testicular cancer 43 Joe Bakhmoutski – Cancer treatment in a time of uncertainty 44 ANZUP trials – testicular 46 Spotlight on kidney cancer 48 The SORCE Trial – then and now 50 ANZUP trials – kidney 52 Spotlight on penile cancer 54 Rare cancers 56 Trials in follow up 59 The importance of your support 60 Make a difference with ANZUP 60 How can you get involved?

ANZUP Cancer Trials Group ACN 133 634 956 ABN 32 133 634 956

61 Noel Castan Fellowship 61 Fundraising heroes 62 Get inspired and host your own 62 How does your donation make a difference? 63 Below the Belt Pedalthon 65 Below the Belt #YourWay 66 #YourWay inspiration

Editor: Lucy Byers. Contributing editors: Gillian Bailey and Abigail Gatling. Graphic design: Designcycle. Cover photo: donated by the Dawes and McJannett family.

4 A LITTLE BELOW THE BELT

67 Thanks to Corporate Supporters and In-Kind Supporters

Message from the Chair, Professor Ian Davis Welcome to this latest edition of “A little below the belt.” Our last edition was published in December 2019. That is seven months plus a lifetime ago, in a strange universe that now seems almost a fantasy. It was just before bushfires devastated enormous parts of Australia and destroyed people’s lives and livelihoods. In those far off times we used to think nothing of going outside, mixing in crowds of people, going to the supermarket, and touching door handles and stair rails, without fearing for our lives. We would sometimes go to places where groups of people would sit down together, and other people would bring you food in exchange for money – can you believe it? Even medicine was practised differently: whole families could be present for a conversation, and we, I’m not joking, would actually touch patients. I wear this weird tubular contraption around my neck even now when I’m in clinic; it has bits that go in your ears, but I’m struggling to remember what the other end does. The bushfires, for all their horror, showed us the very best of our society. People went out of their way to give generously and to support those in need, however they could. Then COVID-19 came along, first as a distant rumour, then a bit of a potential menace, and then perhaps the greatest disruptor we have seen since the world wars. Sadly, the virus brought out the worst of ourselves: old people being pushed over and fights breaking out, so that people could take their massive stocks of toilet paper and pasta, presumably so they could build themselves a nice safe fort at home and others could just make do how best they could, not their problem. And just recently the world seems to have descended into even more insanity, as people are murdered while protesting against the brutality of parts of our society that are vocationally employed to protect us all. Perhaps finally the more fortunate people in our society are starting recognise that indeed some people

face that threat all the time, and that their lives really do matter. A glimmer of hope? It seems to me that in the last few months we’ve had the apocalyptic Four Horsemen of Pestilence, War, Famine, and Death, and you would probably agree that this awful reality show should not be renewed for another season. The virus has not gone away. There will be more waves to come before we can finally access either effective vaccines or treatments, but we should be more informed for these than we were before. There is still rebuilding to be done, of fire-affected buildings, broken lives, and shattered trust. I only hope that our true humanity emerges shining at the end of it; I have faith that it can. Wow, that’s depressing. Thanks for bearing with me while I put it all out there. But what on earth does it all have to do with cancer, and why should ANZUP care about this? Finally, some questions that are easier to answer. We’ve all been experiencing in some ways what people affected by cancer must experience all the time. Pestilence: cancer is a group of horrible diseases, which disrupt our usual comfortable ways of life and thrust us into situations that we could not even imagine before. War: I personally find the military metaphors for cancer very distasteful (“he fought the cancer;” “she lost her battle”), because they imply that if you were only strong enough or tried enough options then you would have won, and the implication therefore is that people who do not emerge victorious must not have tried hard enough. That’s incredibly unfair, and completely wrong, but it is true to say that cancer is War in the sense that you must sometimes mobilise all your resources and supply lines to get yourself and your family through each daily skirmish. Famine: cancer all too often sucks the joy and other things that sustain us out of people’s lives, especially if the disease or the treatment leaves them too frail or vulnerable to enjoy doing the things they would normally do. And Death: well, that one kind of goes without saying.

A LITTLE LITTLE BELOW BELOW THE THE BELT 5 A

None of that is OK. None of that can be allowed to continue. Cancer is unfair: no-one deserves it. Cancer is a terrorist: even when it’s not active, it can instil fear in those who have been affected by it. We’ve all experienced recently just how hard life can be even without cancer; imagine that, and cancer on top of it all? ANZUP exists to change this. We are the Australian and New Zealand Urogenital ANZUP exists to and Prostate Cancer improve outcomes for Trials Group. We people with “below exist to improve the belt”cancers outcomes for people affected by genitourinary cancers: cancers of the urinary tract (kidney, bladder, and similar tissues) and male sex organs (prostate, penis). These “below the belt” cancers, after which this publication is named, collectively account for a large proportion of all cancers and a very substantial fraction of the burden of cancer to the community. Some people find it difficult to talk about these cancers because of embarrassment or squeamishness, and this is understandable; but that only makes it harder for those affected by them, either directly or indirectly. We can only improve their outcomes by finding better ways to treat the cancer, reduce the adverse impact of the cancer and its treatment, and to support people at every point of the process and for as long as they need it. ANZUP is made up of clinicians, scientists, researchers, and community representatives, all of whom work to treat these cancers, or to understand the science behind them, or to raise awareness of them and of the importance of research into them. We look after people affected by these cancers every day. We see where the areas are of unmet need, and we listen to the community when they tell us what we need to improve. We look at the science and what tools are available to us, either in the form of new treatments or new ways of using old treatments, or ways of measuring and assessing the cancer, or providing information or support to people who need it. We also know that this effort is going to continue for a long time, so we need to ensure that the next generation of clinicians and researchers is well trained to continue the work and gets the opportunities they need to do so.

The good news is that ANZUP has continued to function effectively in these times, even when so much else seemed to be collapsing. We have continued our clinical trials, and have even opened a new international trial, much to the amazement of our international collaborators. We have completed important trials, generating new evidence that will change the management of these cancers, and presented this information to the world at international meetings. We have continued our pipeline of ideas, holding Concept Development Workshops aimed at generating the next series of clinical trials; these processes are lengthy and must start well before the preceding trials are finished, so that we always have trials active. We have continued to support our early career clinicians and researchers. We have continued our charity fundraising efforts, all of which go back to support that work. And we are making sure but steady progress forwards. 6 A LITTLE BELOW THE BELT

That has not happened easily or without cost. Our management team rapidly had to reorganise to be able to work safely and effectively from home. We realised quite early that it was not going to be possible to hold our Annual Scientific Meeting (ASM) as planned, in Adelaide in July 2020, although substantial effort and investment had already been put into that meeting. We made the heartbreaking decision to defer the ASM until 2021. Our Below the Belt Pedalthon events have been postponed until 2021. All of this has meant that ANZUP, a not-for-profit charity, has taken a substantial financial hit. Fortunately, our Board and our CEO have been building our resources carefully, and we determined we would be able to survive the lack of our ASM for 2020. We have also been fortunate to experience the generosity of so many people (as is always the case): our international speakers unanimously agreed to come to our rescheduled ASM, which will be in July 2021; our sponsors, partners, and event venues have continued to support us; and our Below the Belt donors saw the importance of the funds they had already raised and agreed to allow them to be kept to support research projects. We are planning future initiatives in 2020, including a “mini-ASM” and other events. I cannot pretend that the problems ANZUP has encountered during this time in any way compare to those experienced by people affected by cancer. I do believe though that we have seen and continue to see the very best of people, who continue to contribute with selfless generosity to the work we do, either through time, money, expertise, advocacy, awareness, or encouragement. That is definitely an experience we share with those affected by cancer, as we frequently hear. We will miss having our ASM this year, not so much because of the science (which is unfailingly amazing), but because of the joy we have in meeting together and bringing our different views and approaches to bear on the challenges we face in common. Everybody involved in ANZUP is there for the same reasons, and everybody is committed to giving of themselves generously to make sure that we achieve our goals. That shared vision was reflected in the theme of our now-deferred ASM: “Clear Vision.” We have a vision of where the world should be and how we can work together to get there. The ANZUP ASM is a wonderful opportunity to refresh those bonds and we look forward to the day when we can meet again safely. So, there is still hope, and there is still love, and there is still joy, and beauty, and generosity. ANZUP brings the best out of people, even in the worst circumstances, and we have shown this to the whole world during this time. Thanks to all of our extended team, who have made it possible. Thanks to you, the reader of this publication: you are reading it because you have been affected by cancer in some way (as have we all) and perhaps are looking for ways to help. You will find practical ways to do that in these pages. And those Horsemen and their nags? We took the War horse and hitched it to our wagon so we can make better progress. We took Pestilence’s to the vet and managed to diagnose and treat it effectively with new approaches developed by our members and tested in a trial. We took Famine’s and gave it the food it needed to be sleek, glossy, and productive again. And Death’s horse? Well, let’s just say we needed some glue to hold the whole thing together.

IAN DAVIS Chair

A message from the CEO, Margaret McJannett

It was late last year when we were planning the theme for our “2020” Annual Scientific Meeting and members of the convening committee piped up and said, “It’s pretty obvious ‘Clear Vision.’” Then came COVID-19 and suddenly we were catapulted into seeing firsthand what a “rapidly evolving health and medical research system” really looks like. While we planned for a tsunami, implementing contingencies in order to maintain productivity, we also needed to ensure the health, safety and wellbeing of the patients, health care professionals, and other staff involved in patient care and research remained paramount. We have seen remarkable collaborations and innovations emerge, eg. alcohol distilleries making hand sanitisers, repurposing 3D printers to develop much needed personal protective equipment, rapid deployment of digitally enabled telehealth, as well as our pharmaceutical partners working closely with us to ensure supply of drugs to patients’ homes. So not quite the ‘Clear Vision’ we were anticipating however as restrictions begin to lift the question remains for us all, what will our new normal look like? Despite COVID-19, we have continued to reach some significant milestones. We activated a new trial, DASLHiCaP and recruited our first patient on 30 April 2020. This study aims to recruit 1,100 patients from over 100 sites across Australia, New Zealand, US, Canada, UK and Ireland. Congratulations to Professor Chris Sweeney, Dr Tamim Niazi and the DASL-HiCAP trial team of investigators, site staff and coordinating centres on this achievement. You can read more about this trial in this edition.

We were delighted that our TheraP trial was featured as an oral presentation at the American Society of Clinical Oncology (ASCO) 2020 virtual meeting on Friday 29 May, with Professor Michael Hofman presenting the interim results. TheraP is the first randomised trial comparing 177Lu-PSMA-617 (Lu-PSMA), a novel radioactive treatment, to the current standardof-care chemotherapy called cabazitaxel for men with metastatic castration-resistant prostate cancer. The TheraP Trial is a partnership between ANZUP and the Prostate Cancer Foundation of Australia (PCFA) with support from the Australian Nuclear Science and Technology Organisation (ANSTO), Endocyte, It’s a Bloke Thing, Movember, CAN4CANCER. ANZUP collaborated with the University of Sydney’s NHMRC Clinical Trials Centre for central study coordination. We are very grateful to all the patients and their families for their participation. We are very excited to soon be opening our latest theranostic trial ENZA-p (ANZUP 1901) . This is an ANZUP-led randomised trial using PSMA as a therapeutic agent (Lutetium-PSMA) and prognostic indicator (PSMA-PET) in men with metastatic castrateresistant prostate cancer treated with enzalutamide. This study is being led by Associate Professor Louise Emmett from St Vincent’s Hospital in Sydney. The study aims to recruit 160 patients, across 12 sites. ANZUP received funding from the Prostate Cancer Research Alliance (PCRA): An Australian Government and Movember Foundation Collaboration, Endocyte (a Novartis company).

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We recently held our first two virtual Concept Development Workshops (CDW) where 14 concepts were presented to our multidisciplinary members. It was great to see how engaged our members stayed whilst using Zoom. The CDW’s are a way of ensuring a pipeline of innovative ideas can be considered and prioritised, with potential support from the Below the Belt Research Fund, over the next 12 months. THE ANZUP CONCEPT DEVELOPMENT WORKSHOP ON ZOOM

While there was further disappointment, and a few tears, with the postponement of this year’s Melbourne Pedalthon, we continue to be overwhelmed by the generosity of the ANZUP community. We are extremely grateful to our friends at the Melbourne Racing Club Foundation and Sandown who have kindly agreed to move the event to 2021. A big thank you to all our riders, donors and sponsors for your understanding and your continued support. Our Sydney Pedalthon in September will also be postponed, however we are working on an exciting new virtual challenge – Below the Belt #YourWay. The challenge is open to all our members, supporters and the general public around Australia and New Zealand. It will not only appeal to the cycling enthusiast but also those who enjoy walking and running, and with your friends, family, colleagues or individually. All in the name of raising awareness and funds for our clinical trials research and keeping us all fit and healthy. You can read more about our exciting new campaign on page 70 or you can visit www.belowthebelt.org.au/yourway to register. Sadly, earlier this year ANZUP’s Deputy Chair Associate Professor Guy Toner announced he would be standing down from the Board in July. A/Prof Toner was pivotal in the initial establishment of ANZUP and has been a director and deputy chair since ANZUP’s inception. Through this time, he has guided the organisation to where it is today. His wise advice and mentorship has positively influenced clinicians and researchers all over the world. Our heartfelt thanks go to Guy and we wish him a truly amazing retirement.

ANZUP is now recognised nationally and internationally for below the belt cancer clinical trials research. This does not happen by chance - it is a consequence of a significant amount of effort from a number of extremely generous people and on top of their very busy usual jobs. We extend our gratitude to all those who continue to show their support to ANZUP, both individuals and organisations who fundraise or support us in their own ways. ANZUP is a not-for-profit organisation. We receive valuable infrastructure support from the Australian Government through Cancer Australia, however, each clinical trial requires its own funding stream in order to proceed. At the moment we rely on applying for grants from various sources, which can take several years and even then, might not be successful. It is therefore critical that ANZUP raises funds to continue our important work. If you are seeking more regular updates from us, we welcome you to join our free initiative, “Friends of ANZUP” to help you stay connected with the work we do. Visit the ANZUP website to sign up: https://www.anzup.org.au/friendsofanzup.aspx

Finally our thanks to the many thousands of patients who participate in ANZUP trials. Each and every one of you help us to improve treatment and outcomes for patients and their families affected by these below the belt cancers. So while not quite the year of ‘Clear Vision’ any of us were anticipating, we have worked together to implement a number of strategies to ensure we meet the objectives of ANZUP: to improve outcomes for people affected with below the belt cancers. I hope you enjoy this edition of ‘A little below the belt’. Please stay well.

MARGARET MCJANNETT CEO, ANZUP

ANZUP TEAM AND COLLABORATORS AT THE DASL-HICAP INVESTIGATOR MEETING IN JANUARY 2020.

8 A LITTLE BELOW THE BELT

Our thanks to Associate Professor Guy Toner Associate Professor Guy Toner has been on the ANZUP Board as Deputy Chair since ANZUP’s inception and played a pivotal role in the establishment of ANZUP, having chaired one of its predecessor organisations, ANZGCTG – Australia New Zealand Germ Cell Tumour Group. He has been the quiet but effective force behind many of ANZUP’S initiatives, including the highly successful Below the Belt Research Fund and more recently the Discretionary Funding Initiative. A/Prof Toner’s leadership has been instrumental and he has been a trusted mentor to many in the clinical community. Earlier this year A/Prof Toner announced he would be standing down from the ANZUP Board at the Annual General Meeting in July as well as retiring from Peter MacCallum Cancer Centre after 30 years of service. A/Prof Toner was a Consultant Medical Oncologist at Peter MacCallum Cancer Centre and Associate Professor of Medicine at the University of Melbourne. He is a graduate of the University of Melbourne and undertook sub-specialty training in medical oncology at the Alfred Hospital before spending 3 years at Memorial Sloan-Kettering Cancer Centre in New York, where he worked in the GU service. He developed a special interest in testicular cancer whilst in New York and his research there formed the basis of his MD (Doctor of Medicine) thesis. He returned to Melbourne to take up a full-time position at Peter MacCallum Cancer Centre in 1990. His clinical and research interests include all urological cancers and he also has an interest in new drug development. In addition he has been an incredible clinician to many patients and their families.

Dear Dr Toner, Laura an dI would jus (and my family a t li nd friend s) for every ke to say a mas s th iv the past ing you have don e thank you e for me five year over s. You have qu us the op ite literally sav ed my lif portunity ea beautiful to have a now tw nd given daughter o, Ivy, wit expected h our sec year old in Septe ond child mber. Aside fro m being a clinician , you hav brilliant and kno wledgeab e always respectf le been poli ul and m t o e, s t importa factual w ith us th ntly hone rou st and treatmen t and foll ghout my diagno sis, ow-up. I was quit e (hopefull looking forward y) to celebr at and it ho the five-year ma rk with y ing nestly w il o l ut without y not be th ou. e same e his year xperienc e The word s ‘thank you’ are hope you no enjoy yo ur retire t enough and we the futur ment and e may ho whatever ld. Thanks a gain Dr T oner. Trav, La ura and Ivy.

A LITTLE BELOW THE BELT 9

The Consumer Advisory Panel’s (CAP) role is to provide advice from a community perspective to the ANZUP clinicians and researchers across a broad range of research proposals. In doing this we are fortunate to have discussions and input with leading experts in this field. The CAP would like to thank and acknowledge A/Prof Guy Toner for the support he has offered the group since we all came together in 2012 as he stands down from the ANZUP Board as deputy chair in July 2020. We have always been impressed by A/Prof Toner’s calm and unassuming manner. We have learned much from him over the years - his considered wisdom and thoughtful and constructive advice and feedback he has provided at the Scientific Advisory Committee meetings, Concept Development Workshops and many other review panels that the CAP have participated on. We know he has provided much more than this to ANZUP, with outstanding leadership and guidance overall. In standing down from his position as Deputy Chair he will be greatly missed for the valuable contribution he has made.

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On a very personal note, I can’t thank A/Prof Toner enough for the very encouraging and caring role he played in looking after our daughter for 5 years. This was challenging not only from a cancer perspective but also in helping guide our family. When we first met A/Prof Toner our daughter was a shy 13-year-old who had been diagnosed with a rare kidney cancer. He was then on a journey with us until she was a grown up 19-year-old who never complained. We know A/Prof Toner looked after many patients and they were all very fortunate to have experienced his kindness, patience, respect and expertise. We hope we will continue to see A/Prof Toner at future ANZUP meetings as he has much to offer in many ways, particularly mentoring others. We wish A/Prof Toner all the best as he moves closer to a very well-deserved retirement after a rewarding but very challenging and successful career in medical oncology and research. Thank you always.

BELINDA JAGO CAP Chair

Consumer Advisory Panel (CAP) update By Belinda Jago, CAP Chair

Since I last wrote for this magazine 6 months ago, little did we know what lay ahead. With the arrival of the COVID-19 pandemic, life as we knew it, was turned upside down. Personally, I was on a holiday that ended a week early as we had to come home. Then life changed to working from home and staying at home. Sadly, so many people have been significantly affected by the pandemic, not only with their health, but also financially and emotionally. If you are reading this article you may have been affected by a cancer diagnosis, either yourself or a close friend or family member. You are already dealing with a serious health issue, and the current climate has added another layer of complexity and uncertainty in your life. Some of our CAP members are cancer patients and have faced the same issues around treatment, such as attending doctor’s appointments when your immune system is already compromised and you are more vulnerable to infections. For patients currently on clinical trials who usually attend regular face to face clinic visits, there have been changes. There are questions around, ‘how is this going to work’, ‘how will this impact my treatment and longer term outcomes’, which are difficult issues to deal with. ANZUP’s chair Professor Ian Davis met with the CAP virtually late in March 2020 to seek our feedback on how we all felt about continuing with face to face clinic consultations and treatments. We had to admit we were all feeling pretty nervous at that time and we just wanted to stay home.

THE ANZUP CAP ZOOM MEETING

ANZUP has taken a proactive approach and reviewed their clinical trials portfolio, and considered the impact and safety for both the patient and health professionals. It has created a flurry of activity in considering what needed to change to reduce the risk of exposure to COVID-19. Ensuring the safety of patients and their families, health professionals and their employees and all clinical trial staff was of utmost importance to ANZUP. There have been positive outcomes during this challenging time, including virtual meetings, saving time and travel, as well as reduction in expenditure. Telehealth has now become a priority. It will hopefully help address how clinical trials can be inclusive for all those social distancing and in isolation as well as cancer patients located in rural and remote areas. Telehealth and teletrials will benefit so many people as they will be able to access clinical trials and better healthcare in general, not just now but also in the future. It is a very anxious time for patients, carers and their families who already have a cancer diagnosis to worry about. Rest assured, you are in good hands with the health professionals and front line workers who are working tirelessly to deliver exceptional treatment and healthcare. We thank them for protecting and improving the health and well-being of people in the community, in particular ANZUP’s clinical members. In addition, clinical trials are still continuing so speak with your healthcare team if you would like to know more. Most importantly, keep practising social distancing and good hand hygiene. Hopefully when I again write for this magazine, times have changed for the better. On behalf of the ANZUP CAP, please stay safe and healthy.

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oin J o t E FRE

Friends of ANZUP questions answered, community and clinical trials Friends of ANZUP aims to provide:

After a cancer diagnosis there is shock, questions and a whirlwind of emotions. You, your family and friends may worry about what the diagnosis means for your present life as well as your future.

• I nformation about the benefits of clinical trials and how to access them;

Many decisions will need to be made including how to tell family and friends, how to make sure children are looked after, whether to keep working and how to manage financially and also what treatment to have and where to have the treatment.

• Information about the clinical trials research conducted by ANZUP; • Biannual community magazine ‘A little below the belt’ featuring regular updates and stories from health professionals, researchers, cancer survivors and cancer trial participants;

Finding reliable information and the right type of support can be the first step in answering questions when you are feeling overwhelmed. There are many different support groups and a multitude of internet sites with a lot of information, both fact and fictional. Friends of ANZUP was established to connect people whose lives have been affected by prostate, kidney, bladder, penile and testicular cancer, ie below the belt cancers. If you are seeking more information about any of these cancers, would like to hear from people who have been faced with the same challenges, and if you have questions about clinical trials, what they are and if there is a clinical trial suitable for you – then this program could provide some answers.

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12 A LITTLE BELOW THE BELT

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• U pdates from the ANZUP clinical community

2019

By choosing to join the Friends of ANZUP community you will be at the forefront of important research into “below the belt” cancers through clinical trials. You will also have access to the latest news in below the belt (prostate, testicular, kidney, penile and bladder) cancer trials conducted by ANZUP as well as the many ways you may want to get involved in raising awareness or funds to support vital clinical research.

And remember, if you are wondering if a clinical trial is the correct treatment pathway then consider each point below: • Participation in a clinical trial may increase the total number of treatment options available to you – even if you have not yet had all the standard (current) treatment options. • You could have access to treatment not yet commercially available, which might work better or be safer than current treatment options.

• M aking the decision to take part in a clinical trial may make you feel you have more control over your situation and that you are taking a more active role in your treatment. • Your cancer care team will probably provide more attention and more careful monitoring of your condition and possible side effects of treatment if you take part in a clinical trial. • And importantly, you might help others who have the same cancer type in the future by helping advance cancer research. It’s only through clinical trials we can improve treatment options and outcomes for over 27,000 Australians diagnosed with “below the belt” cancers each year. By joining our community, you can take control of your treatment, be better informed, hopefully become an advocate for clinical trials and assist us in raising awareness of the benefits of clinical trials research and ultimately help us continue to fight cancer below the belt. To find out more visit https://www.anzup.org.au/ friendsofanzup.aspx

“Often people are so frightened by the word “cancer” and just hearing it can be so traumatic, regardless of the diagnosis; they hear nothing else – and I was no different. Cancer takes away the ability to be obliviously confident we will grow into old age and it takes time to learn to respect it, not fear it. On the other hand, there’s a lot to be said for the raised awareness and friendships people find through cancer. This of course is a very well researched and important topic and one ANZUP researchers consider when designing their studies. Friends of ANZUP is a great example of how patients’ voices are heard and acknowledged.” Leonie Young, ANZUP Consumer Advisory Panel member

A LITTLE BELOW THE BELT 13

Clinical trials

The importance of clinical trials and research With the current worldwide pandemic, we are hearing more and more about clinical trials. Since COVID-19 appeared in November 2019, more than 1100 clinical studies have been registered globally with several trials being conducted in Australia. In addition, an increasing number of Australians are putting their names forward to participate in COVID-19 clinical trials for medicines as a vaccine or treatment. ANZUP was established over a decade ago to conduct clinical trials to improve treatments and outcomes for bladder, kidney, testicular, penile and prostate cancer. Many people are unaware of the importance of clinical trials, what they are, what they involve and why they are important. So ANZUP’s goals include building on and developing high quality, cutting edge clinical trials but also to increase awareness and participation in trials.

“Clinical trials are the main thing that we do. This is how we generate the evidence that allows your health professional to give you advice and helps you to make decisions about your treatment.” Professor Ian Davis, Chair ANZUP

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What are clinical trials? Clinical trials are essential for discovering new treatments for diseases, as well as new ways to detect, diagnose, and reduce the chance of developing the disease. Clinical trials can show researchers what does and doesn’t work in humans that cannot be learned in animals or in the laboratory, and at the same time test for any potential side effects. Every day hundreds of people are invited to participate in clinical trials to test new treatments and devices. Clinical trials are conducted across four phases and people can be invited to participate in any of these phases. The trial process, across all the phases, can take 5-10 years or more.

What is a randomised controlled trial? The best way to compare a new treatment to the standard or currently approved treatment is in a randomised controlled trial. What does this mean? In such a study, participants are randomly assigned to either the standard (control) or new treatment. This is done by using the computer equivalent of tossing a coin – and the process is known as randomisation.

Why are clinical trials important? Without people participating in clinical trials, groundbreaking treatments and devices would never make it to market. Further awareness is needed as only a small percentage of eligible people take part in clinical trials. In addition, if you take part in a randomised trial you may receive a treatment that is better than standard care and you are often more closely monitored than under routine care outside of the trial setting.

Clinical trials Clinical trial stages Phases one and two The early studies, called phase one and two, test the treatment’s safety in a small group of people. This means ascertaining that the new treatment has acceptable side effects.

Phases three and four Phases three and four are much larger studies and test whether the treatment actually works or is effective for its intended purpose. It is also assessed for whether it is beneficial to patients compared with the standard or current treatments for that condition.

LAB STUDIES

HUMAN SAFETY tens of participants

EXPANDED SAFETY AND EFFICACY

EFFICACY & SAFETY thousands of participants

hundreds of participants

Preclinical

Several Years

Phase 1

Phase I/II

Days or Weeks

Weeks or Months

Phase III

Several Years

DURATION OF TRIAL

“I think I thought being on a trial was at the cutting edge of treatments and I was being given the best shot at getting my cancer under control… You hear and see positive stories about clinical trials so I was excited to have this option.” ENZAMET prostate cancer trial participant

For some health conditions, participating in a clinical trial provides the only chance to receive a potentially beneficial treatment that may take many years to become commercially available. Also, results of a trial will be used to guide clinical practice and will benefit future patients. In the case of COVID-19, results of the vaccine trials could impact millions of lives, just as a prostate cancer trial undertaken by ANZUP could benefit the 16,700 diagnosed patients in Australia. Sometimes clinicians may think a new drug is better than a current treatment, or vice versa. The only way we can know for certain is by conducting clinical trials. Research helps health care professional be systematic in their practice and ultimately provide better clinical care. Australia is home to some of the world’s best researchers and health professionals and ANZUP is very lucky to work with a lot of them. So clinical trial teams, with the addition of clinical trials participants, are so important to ensure discoveries, advances and the best possible treatments and outcomes continue to become available to the wider population and improve the standards of care.

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Telehealth and teletrials Australasian Teletrial Model

Primary Site

Satellite Site

Telehealth

Specialists

Patients and Families

Clinical Trial Coordinators

Medical Officers

Specialist Pharmacy, Nursing and Allied Health Clinicians Administration Support Officers

Patients are consented, recruited and managed at satellite sites in partnership between clinicians from satellite and primary sites.

Primary and satellite sites are connected through tele-health models of care.

(Larger centres may have specialist doctors, nurses, pharmacies and allied health clinicians)

Primary Site Satellite 2

While telehealth has existed in Australia for some time, it’s entirely possible many patients and caregivers hadn’t heard about it until the COVID-19 outbreak when the government announced a new telehealth program as part of its response to ‘flatten the curve’. Rural communities have had access to telehealth for a while - but when COVID-19 led to increased social distancing and isolation measures, there was a need to expand the offering. Telehealth allows people to access essential health services in their home while they undergo self-isolation or quarantine and it reduces the risk of exposure to COVID-19 for vulnerable people in the community. In addition, telehealth is a way of delivering health services remotely, either through telephone, video conferencing or other forms of communication technologies. It allows health services to be brought to patients who are unable to be in physical contact with a health service provider and the consultation can be done on various platforms such as FaceTime, a phone and Skype. Teletrials builds on the telehealth model and increases access to clinical trials for people with cancer living in rural and remote locations, or in isolation due to COVID-19. Teletrials also allows trial recruitment and activity to continue and expand.

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With/without Trial Coordinators

Satellite 1

Trial Cluster

(Satellite sites can be regional, rural or larger metropolitan centres.)

Nursing, Pharmacy and Allied Health Clinicians

Satellite 3

(Source: COSA implementation guide. Colour figure can be viewed at wileyonlinelibrary.com)

ANZUP is embarking on its first teletrial under the guidance of Dr Craig Underhill of Border Medical Oncology in Albury. The UNICAB trial will now also be conducted as a teletrial and increase the pool of patients who will be able to participate. UNICAB is a phase II trial aiming to find how safe, tolerable and effective a new treatment called cabozantinib is for non-clear cell kidney cancer.

“Regional cancer patients experience several disadvantages including lower survival rates, due to healthcare access differentials…. a Teletrials Program aims to reduce the barriers for regional patients with cancer to access clinical trials, including travel, cost and social disruption.” Dr Craig Underhill

What is a teletrial? A teletrial allows a clinician at a larger centre (primary site) to enrol, consent and treat patients on clinical trials in collaboration with smaller regional and rural centres (satellite sites), allowing patients to participate closer to home, and during COVID-19 social distancing. Participation in clinical trials is recommended as the best option for many cancer patients. The teletrial model means access to novel, ground-breaking treatments for everyone no matter where they are based â&#x20AC;&#x201C; in isolation, regional, rural and remote areas. This model has the potential to connect larger centres, even within the same city, and improve the rate of recruitment to highly specialised clinical trials. Medical oncologists and trial coordinators from primary trial sites can use teleoncology to help obtain consent, recruit, treat and monitor patients at satellite sites, and at home, during routine or trial-specific consultations depending on the type of study. And just as with face-to-face clinical trials, teletrials also takes into consideration the requirements for proper conduct to ensure the trials are both safe and ethical.

Will telehealth and teletrials continue to grow? Telehealth has already expanded in response to the coronavirus crisis so it is sure to become more widely accepted and even easier to use in the future. There is no reason why telehealth tools wonâ&#x20AC;&#x2122;t become an integral part of healthcare systems worldwide and digital health is a quickly developing tool for regional patientsâ&#x20AC;&#x2122; access to health services. ANZUP hopes the success of the UNICAB teletrial will help the health service challenge of meeting recruitment targets and bring cancer treatments and trial participation to the broader community.

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Finding calm in the face of cancer and COVID-19 A cancer diagnosis has the ability to completely turn your world upside-down. It can often put plans on hold, or derail them completely. It brings uncertainty. It is emotional and it can be scary. While it is completely natural, being anxious or stressed about your cancer can often make you feel worse in an already distressing time. However, certain activities and techniques can help you reduce your stress and cope with the emotions that come with a cancer diagnosis. While your emotions and moods can change from hour to hour, weâ&#x20AC;&#x2122;ve put together some tips for when you recognise that you need to reset and regain your sense of calm.

Keep your routine

There is something comforting in having a steady, familiar routine or daily ritual. Whether it is having a cup of coffee on the veranda, taking the dog for a walk, or playing the guitar, try to keep these routines going if you are feeling able to. This will help inject structure back into your life and adds a sense of normality in an otherwise unsettling time.

Stay connected

Cancer can be isolating; it is an experience that not everyone goes through, but it is not a journey that you need to walk alone. Reach out to your friends, family or colleagues, whoever in your life that is positive and uplifting for you. You might also like to join a local community club or cancer support group to meet new people with similar interests or experiences as you. Having a support network is an important part of dealing with your emotions.

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Plan a holiday

When faced with uncertainty, we often tend to hold off making plans. However, plans are essential for keeping your spirits light and regaining a sense of control over your future. Take the time to research and plan a holiday when we can, watch movies or TV shows about your destination, meet up with your friends or family to plan your trip. While you may not go ahead and book your trip at this point, discovering new things and having something exciting to look forward to will keep your mind busy and help reduce stress.

ind a way to F switch off

Meditation, yoga and mindfulness can be useful tools to help you relax and switch your mind off. Reflect on what has made you feel calm in the past and set some time aside to practice it each day. There is no wrong or right way to do this, so if watching golf on TV helps you switch off, go for it!

Help someone else

In times of uncertainty, it is easy to lose your sense of purpose in life. One way to regain that is to help others. Helping others not only makes them feel good, but the satisfaction from doing a good deed makes you feel good too. So why not offer to help a friend or colleague or volunteer at an organisation. Or, share your story and support others going through a similar situation to you. Offering to help others will boost your endorphins and make you happier.

Out with Cancer study shining a light on LGBTQI+ experiences of cancer The Out with Cancer study is examining LGBTQI+ (lesbian, gay, bisexual, trans, queer and intersex) experiences of cancer from the perspective of people with cancer, their carers and healthcare professionals.

LGBTIQ+ people often have unique needs during and after cancer and represent an invisible diversity in cancer care. Previous international findings suggest LGBTIQ+ communities experience a disproportionate cancer burden and face unique psychosocial challenges, such as higher rates of cancer related distress and sexual concerns, lower levels of family support, difficulties in accessing general health care or cancer services, gaps in patient-provider communication and lower satisfaction with cancer care. Professor Jane Ussher from Western Sydney University’s Translational Health Research Institute says outcomes of the Out with Cancer study will be critical in improving the health and wellbeing of sexual and gender minorities as well as intersex people.

How to take part We would value hearing about your personal experiences as an LGBTQI+ person who has had cancer, or as a partner, family member or other carer for an LGBTQI+ person with cancer. Take part here: www.westernsydney.edu.au/outwithcancer We would also like to hear from healthcare professionals working in cancer medicine and cancer care. Take part here: www.westernsydney.edu.au/ out-with-cancer/healthcare-professionals

More information For more information about the study please contact: outwithcancer@westernsydney.edu.au

“The unique experiences and needs of LGBTQI+ people have been largely overlooked by Australian cancer researchers, policy makers, and service providers. This study will help address insufficient knowledge about health care needs, outcomes, lived experiences and effective interventions for LGBTQI+ populations. “This will also be the first study internationally to examine the experiences of non-binary, transgender, intersex and young LGBTQI+ cancer survivors.” Funded by an Australian Research Council Linkage grant, the study is based at Western Sydney University, in partnership with the Prostate Cancer Foundation of Australia, Cancer Council NSW, National LGBTI Health Alliance, ACON, Breast Cancer Network Australia, CanTeen, UTS, Melbourne, La Trobe, New South Wales and Monash universities as well as national and international stakeholders in cancer, LGBTQI+ health and ANZUP. The study aims to improve knowledge and services for this often overlooked population.

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New research bridges bench to bedside The route to developing and discovering new and improved ways to diagnose and eventually treat cancer is rigorous, long and expensive. Before human clinical research, in the form of clinical trials can take place to investigate these novel treatment approaches, many years of research has to take place in laboratories to provide a basis for the trials. This laboratory research is often referred to as basic science. Basic laboratory research is undertaken to better understand the mechanisms of the disease, on a cellular level, whereas clinical research explores how this information impacts on diagnosis, treatment and potentially even prevention of these diseases. CLINICAL RESEARCH

BASIC RESEARCH

understand disease

bridges the gap

treat the disease

TRANSLATIONAL RESEARCH

What is translational research? Thanks to recent advances in science and technology, connecting what has been learnt from basic research to the clinical research is no longer a one-way road. The learnings that come out of clinical research is being fed back in to inform more basic research, which allows for a faster and more effective research cycle. This research is known as Translational Research. Translational Research is the process of turning observations in the laboratory, clinic and community into interventions that improve the health of individuals and the public – from diagnostics and therapeutics to medical procedures and behavioural changes. Translational science is the field of investigation focused on understanding the scientific and operational principles underlying each step of the translational process. Translational research brings together a range of experts to collaborate to further understand and advance cancer research. By bringing together scientists, researchers, doctors and allied health professionals from different disciplines, research can be dissected and refined through a rich range of differing perspectives. By knowing more about a disease, we can determine how best to diagnose and treat the disease.

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Translational research can also happen following a clinical trial. This can involve taking the results from the trial and helping to shape specific treatment processes or guidelines that can be used by other health practitioners in the future. The translational research carried out following a clinical trial can also help to deepen the understanding of why some patients respond well to certain treatments, whereas other sufferers do not. Understanding these person-specific differences can help inform the doctors choices and lead towards personalised treatment and care for patients.

Translational research ‘translates’ research findings into practical medical treatments and processes. None of this work would be possible without the patients and families who generously donate tissue and blood samples that underpin our Translational Research. These high-quality samples, are crucial to helping us answer key biological questions that could ultimately shape our treatment of urological cancers. Patients who participate in ANZUP trials are asked to consent to the collection of blood and tissue samples which can then be used to conduct research for these and other studies in Australia and/or overseas.This research may not benefit them specifically but may help people in the future who have the same kind of cancer. It is optional for patients to donate their blood and or tissue samples for research and we are immensely grateful to our patients who do generously provide these samples to help our Translational Research endeavours. We are building a very strong translational focus across all our ANZUP trials and we look forward to sharing more information about these Translational Projects that are being rolled out in the next edition of ‘A little below the belt.’

Spotlight on prostate cancer The prostate is a small gland about the size of a walnut. It is found only in men and forms part of the male reproductive system. It sits below the bladder, near nerves, blood vessels and muscles that control erections and bladder function. These muscles include the pelvic floor muscles, a hammock-like layer of muscles at the base of the pelvis.

16,700+ new diagnoses in Australia each year

63%

of cases diagnosed in those over 65 years

3,000+ deaths

in Australia each year

What is prostate cancer?

Prostate cancer symptoms

Prostate cancer develops when abnormal cells in the prostate gland grow more quickly than in a normal prostate, and in an uncontrolled manner. Prostate cancer is generally a slow growing disease and a lot of men with low grade prostate cancer live without symptoms, without it spreading and becoming life-threatening for many years. However, high grade disease spreads quickly and can be harmful. Appropriate management is very important.

The symptoms can include:

Prostate cancer is the second most common cancer diagnosed in Australia and the fourth most common cause of cancer death. One in seven men will be diagnosed with prostate cancer by the age of 85. It is more common in older men, with 63% of cases diagnosed in men over 65 years of age. In 2020, it is estimated that 16,741 new cases of prostate cancer will be diagnosed in Australia. The five-year survival rate for men diagnosed with prostate cancer is 95%. Nearly all patients who present with localised disease will live beyond five years. In 2020, it is estimated that there will be 3,152 deaths from prostate cancer in Australia.

• Frequent urination, particularly at night; • Pain on urination; • Blood in the urine; • A weak urine stream; • Pain in the pelvis or back. More widespread disease often spreads to the bones and causes unexplained weight loss, fatigue and pain.

Causes of prostate cancer Your risk of prostate cancer can be increased by some of the factors below: • A ge, increasing greatly if you are aged over 50 years; • Family history of prostate, breast or ovarian cancer; • A diet high in fats and low in fresh fruit and vegetables; • High testosterone levels.

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Spotlight on prostate cancer Treatment options Treatment and care of people with cancer is usually provided by a multidisciplinary team, i.e a team of health professionals, both medical and allied health. Your health care team will help decide the most optimal course of treatment and take into consideration: • the stage of the disease; • the location of the cancer; • the severity of symptoms; • your general health and wishes. Treatment may take various forms and may not be recommended straight away. Options include: 1. Watchful waiting where you might be monitored in case symptoms develop or change. 2. A ctive surveillance when you will likely have regular blood tests to check your PSA level, regular digital rectal examinations, and maybe ultrasounds or biopsies. If the cancer starts to grow or there are signs it is worsening, you might begin treatment. 3. S urgery will become an option if the tumour has not spread outside the prostate. The prostate and some of the surrounding tissue will be removed, including the seminal vesicles. This is called a radical prostatectomy.

6. H ormone therapy involves reducing the levels of certain hormones in the body, so the cancer can slow its growth or even shrink. Hormone therapy for prostate cancer is also called androgen deprivation therapy (ADT). 7. C hemotherapy can also be used to treat prostate cancer. 8. Immunotherapy for prostate cancer works by helping a patient’s own immune system fight back against cancer cells. It is used to treat advanced cancer or cancer that has spread.

Clinical trials New drugs and treatment approaches are constantly being developed and researched. New combinations of different strategies and therapies, as well as the development of new drugs, are constantly being trialled and tested to see if they can further improve treatment options for men with advanced prostate cancer and their quality of life. Please talk with your doctor to see if there is a clinical trial suitable for you. You can read more about ANZUP prostate cancer trials on page 30.

4. Radiotherapy can take two forms: a. external beam radiation therapy – where a machine outside the body directs radiation towards the prostate gland b. i nternal radiation therapy (brachytherapy) – where small radioactive ‘seeds’ are placed inside the prostate. 5. C ryosurgery involves inserting long needles through the perineum into the prostate. Very cold gases are then passed through the needles, which freezes the prostate and destroys cancer cells.

References: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/cancer-rankings-data-visualisation https://www.cancer.org.au/about-cancer/types-of-cancer/prostate-cancer/ https://www.prostate.org.au/awareness/for-recently-diagnosed-men-and-their-families/advanced-prostate-cancer/treatment/are-there-new-treatments/

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A LITTLE BELOW THE BELT 22

New class of targeted radioactive treatment effective for men with metastatic prostate cancer

TheraP is the first randomised trial comparing a novel radioactive treatment called 177Lu-PSMA-617 (Lu-PSMA), to the current standard-of-care chemotherapy called cabazitaxel for men with advanced prostate cancer. The men who have taken part in this trial had prostate cancer that had already progressed after standard chemotherapy. This exciting trial is a partnership between ANZUP Cancer Trials Group and the Prostate Cancer Foundation of Australia (PCFA) with support from the Australian Nuclear Science and Technology Organisation (ANSTO), Endocyte, It’s a Bloke Thing, Movember and CAN4CANCER. This trial has now reached a point where interim results have been reported at the American Society of Clinical Oncology Virtual Meeting 2020 – the largest annual oncology scientific meeting – at the end of May 2020.

“This clinical trial provides compelling evidence that Lu-PSMA represents a new class of effective therapy for men with advanced prostate cancer. The ability to see what you treat by using the same molecule for both scanning and treatment is remarkable. This enables personalised and patientcentred care where patients most likely to benefit can be carefully selected...” Study Chair Professor Michael Hofman

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This unique treatment involved two distinct parts: 1. Firstly, a positron emission tomography (PET) scan is used to ‘map’ the cancer. This is done by injecting a radioactive molecule called gallium-68 attached to a small molecule that then attaches to prostate specific membrane antigen (PSMA) on the surface of prostate cancer cells in the body. The cancer cells then ‘light up’, showing exactly where the disease is and enabling identification of patients that may benefit from this new therapy. 2. The second part is the therapy itself: the Lu-177 radionuclide is attached to a similar molecule used in the scanning process, and Lu-PSMA is administered to the patient, targeting the tumours and killing the cancer cells while minimising damage to surrounding normal tissue. High levels of protein specific antigen (PSA) may be an indicator of prostate cancer. So the main result of the TheraP trial, measured at the end of the study, was to see if this new radioactive treatment worked and to compare the effects of the two treatments on a change in PSA. In 66% of men it was found PSA was reduced by 50% or more in the group who received Lu-PSMA compared to a 37% reduction in the group who received cabazitaxel. Results of the trial also demonstrated the treatment had less severe side effects than chemotherapy. Patient follow-up is ongoing with initial results suggesting the new treatment may delay progression of prostate cancer.

“This is a great example of an academic clinical trial that has built on work done in Australia, supported by a large group of funders and stakeholders, performed by an outstanding group of clinicians and researchers, supported by the community, with amazing contributions from the trial participants, in a disease setting where we really need better outcomes. Just getting it done is a major achievement, but we have also shown that this new treatment can benefit some men with advanced prostate cancer,” ANZUP Chair, Professor Ian Davis.

PROFESSOR MICHAEL HOFMAN BEING INTERVIEWED ABOUT THE THERAP TRIAL.

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New era in nuclear medicine Associate Professor Louise Emmett is the Director of Theranostics and Nuclear medicine at St Vincent’s Hospital Sydney. She has been instrumental in developing the radiopharmacy initiative on the St Vincent’s Campus and has introduced multiple new radioisotopes for clinical and research purposes. The St Vincent’s Theranostics Department is highly published in both PET imaging and radionuclide therapy. A/Prof Emmett has a strong track record in multi-site multidisciplinary trials run across Australia, in addition to undertaking early phase clinical trials on the St Vincent’s Campus. She believes in the power of clinical research to optimise treatments and improve the quality of life for patients. A/Prof Emmett is the Principal Investigator of the new ENZA-p Trial (ANZUP 1901) being rolled out across 12 cancer centres across Australia. Tell us about theranostics and nuclear medicine? How is this changing practice for the treatment of prostate cancer? The whole change in prostate cancer diagnosis and treatment with theranostics started in about 2011. A publication at this time demonstrated that a small molecule ligand PET agent (PSMA) in mice had excellent binding to the cancer cell and rapid renal clearance. This was a massive change from the antibodies that had previously targeted the same receptor, but with poor results. This new peptide was validated as a PET agent for prostate cancer, then as a therapy agent in prostate cancer - all in quick succession. It has been a hugely successful benchtop to bedside story.

Theranostics is a combination of the terms therapeutics and diagnostics. Theranostics is the term used to describe the combination of using one radioactive drug to identify (diagnose) and a second radioactive drug to deliver therapy to treat the main tumour and any metastatic (cancer that has spread from the original site to other organs or tissues in the body) tumours.

ASSOCIATE PROFESSOR LOUISE EMMETT PRESENTING

How did the ENZA-p trial come about? The birth of ENZA-p was really all about treatment failure and how to prevent it. In our first pilot trial of Lu-PSMA therapy in men with advanced-stage prostate cancer at St Vincent’s, the first few men we treated did not respond at all. We discovered it was because their PSMA PET screening scans did not have bright enough disease (not enough lutetium would be able to enter the cell). This really got us thinking about how to increase the PSMA receptor on the cell and how to improve treatment responses in all men. As it turns out - enzalutamide does exactly that. It dramatically increases PSMA receptor expression in the prostate cancer cell. It is also a radiation sensitiser, and in cell models it increases prostate cancer cell kill if teamed up with Lu-PSMA. It seemed like a match made in heaven. ENZA-p is all about seeing whether that is correct. It is also about identifying predictors for treatment response - so we can tailor treatments more carefully to the needs of the individual. What is the aim of this trial? The ENZA-p clinical trial aims to compare the effectiveness of enzalutamide in combination with Lu-PSMA, versus enzalutamide alone for the treatment of prostate cancer. This is a randomised trial, so half the men will be assigned to receive Lu-PSMA and enzalutamide, and the other half to receive enzalutamide alone. We plan to enroll 160 participants across Australia.

A LITTLE BELOW THE BELT 25

Will this trial be suitable for anyone with prostate cancer? No. The trial is in men who have been on hormone treatment that is no longer effective. It will be enrolling men who have risk factors for early treatment failure using single agent therapy alone and men who have not yet had chemotherapy. Your thoughts on using this type of treatment for other below the belt cancers? The treatment that we have been using in prostate cancer (PSMA) is unique to prostate cancer at the moment because it is a receptor that is expressed by prostate cancer cells, and not by other cancers. We do get PSMA uptake in other cancers â&#x20AC;&#x201C; but that is due to PSMA expression in the blood vessels of rapidly growing cancers. We do not yet know if the treatment is effective in these cancers. However, in renal cell cancers, which are very vascular - it is definitely a possibility. Further, with the rapid advancement in knowledge for these new treatments, we may find new receptors that can effectively target the other below the belt cancers. Research is the key to this.

Nuclear medicine scans can help doctors find tumours and see how much the cancer has spread in the body (called the cancerâ&#x20AC;&#x2122;s stage). They may also be used to decide if treatment is working. These tests are painless and usually done as an outpatient procedure.

Why do you think clinical research is so important? I think clinical research is hugely important, and fun. You can be a great doctor and help your patients one at a time. But with clinical research, you can help make changes in practice that can improve the lives of many. That is immensely satisfying and it is something that ANZUP is so good at.

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Enzalutamide is a potent hormone therapy that prevents testosterone from reaching prostate cancer cells, thereby stopping cancer growth. It is already widely used in men with prostate cancer that has stopped responding to standard hormone treatments (castration-resistant prostate cancer). However, most cancers become resistant to enzalutamide over time, with almost 1 in 4 being resistant from the start of treatment. Many prostate cancers, in particular those that have spread or become resistant to hormonal therapies, have a substance on their cell surface called prostate specific membrane antigen (PSMA). Lutetium-177 PSMA (LuPSMA for short) is a new treatment in advanced prostate cancer. Lu-PSMA is a radioactive molecule that attaches to the surface of prostate cancer cells throughout the body. This drug is given as an injection through the vein and allows targeted radiation to be delivered directly to prostate cancer cells. Smaller pre-clinical studies have demonstrated synergistic effects by combining Lu-PSMA with enzalutamide. It is possible that Lu-PSMA can prevent early resistance to enzalutamide, extending the time that men benefit from treatment.

DASL-HiCaP trial led by ANZUP now open

In April we were excited to announce the DASL-HiCaP trial enrolled its first patient. This marked the start of the journey to recruit and follow up 1,100 eligible patients over 100 cancer centres across Australia, New Zealand, US, Canada, United Kingdom and Ireland. The DASL-HiCaP trial, led by ANZUP’s Professor Christopher Sweeney and Dr Tamim Niazi, will see if a new oral drug, darolutamide, combined with the current best treatments, can improve outcomes for men with high risk prostate cancer that has not spread beyond the prostate area. Previous studies have shown promising results for darolutamide preventing progression of prostate cancer and improving survival for men with an advanced form of this disease. This is a randomised controlled trial, which means in addition to best standard treatments, half the participants on the study will receive darolutamide and the other half will receive placebo. “We know clinical trials are the only way to find out the safety and effectiveness of new treatments and whether they should become the new gold standard for treatment in the future,” said ANZUP Chair, Professor Ian Davis. Prostate cancer remains the most common cancer in Australian men and the leading cause of cancer related deaths for men in developed countries. So the outcomes of the trial will be measured in terms of whether the addition of darolutamide decreases the risk of spread of prostate cancer to other parts of the body as well as improving quality of life and potentially decrease the risk of prostate cancer death.

“DASL-HiCaP is specifically designed to assess whether the potent hormone treatment can lessen the risk of recurrence of prostate cancer in men with prostate cancer with features with a high risk of spreading to other parts of the body. The patients in this study will be men treated with testosterone suppression along with radiation, or radiation after surgery, and who are at significant risk of the cancer relapsing. Our hope is that this trial might show new ways of improving outcomes for these men with prostate cancer,” Professor Sweeney, Study Co-Chair

ANZUP acknowledges and thanks BAYER for their product and funding support for DASL-HiCaP Trial. https://anzup.org.au/content.aspx?page=prostate cancertrialdetails

A LITTLE BELOW THE BELT 27

Dr Felicia Roncalato is ANZUPâ&#x20AC;&#x2122;s senior clinical research fellow and a medical oncologist. Dr Roncalato explains the importance of the DASL-HiCaP trial. Why is the DASL-HiCaP trial important? The trial is important for men with very high risk localised prostate cancer because despite the current standard of care, (which includes radiotherapy with hormonal blockade for a year or more), within 5 years, the disease can grow back in a subgroup of men. Therefore, this trial aims to demonstrate if using darolutamide, (in addition to standard care), will be better than current standard care and lead to improved outcomes and potentially survival. Have there been any similar prostate cancer trials? If not, why is this the first? There are already published trials showing the safety and effectiveness of darolutamide in men with prostate cancer which has spread beyond the prostate. However, this is the first trial to see if darolutamide improves outcomes when given earlier in the disease with radiotherapy, when it is localised to the prostate. In this setting it is the first study to also include chemotherapy in addition to radiotherapy as one of the standard care options. What is the significance of it being an international trial? Many clinicians are collaborating globally to open this trial and recruit patients in many countries including USA, UK, Ireland, Canada and New Zealand. This will give many men from around the world a chance to be part of this exciting trial to help work out the safety and effectiveness of adding darolutamide to current standard care. This may also mean recruitment to the trial may be quicker and we will know earlier if adding in darolutamide to standard care improves outcomes for these men.

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Will recruitment for this study be difficult? It should not be difficult to recruit men to this study as prostate cancer is common, and we are looking for a particular subgroup of men who have prostate cancer with high risk features. We also already know from other trials that darolutamide is a safe medication to take. If this trial has positive outcomes will it significantly change treatment and outcomes for this group of prostate cancer patient? If this trial has positive outcomes, it will significantly change how we treat men with localised prostate cancer and potentially improve outcomes including survival. We are also looking at other important data such as quality of life and cost effectiveness. What is your role in this trial? Can you explain what your role involves, i.e. your day in relation to a clinical trial? My role is senior clinical research fellow for ANZUP. This means I have helped to develop the trial and its protocol, and will be assisting clinicians with queries in enrolling men onto the trial and helping answer any questions regarding the trial conduct and safety of all men enrolled. One of my roles is to work with our team at the Clinical Trials Centre and ANZUP to ensure the data we are collecting from men enrolled on the study is of high integrity and quality. Once the study has completed its recruitment I will also help with analysing the data to see if darolutamide improves outcomes for men when added to standard of care. I am also a site investigator on the study and will be enrolling my own patients onto the study. Will recruitment and participation for this trial be affected by COVID-19? We are all dealing with the devastation around the world with the COVID-19 pandemic, and are collectively involved with service planning for our patients at hospitals and in the community. During the pandemic, where possible, sites for the trial are still opening with standard restrictions in place as directed, and we have already enrolled our first patient onto the trial! The safety of all men participating in our trials remains our first priority and we will continue to enrol patients where sites are able to during this time.

ANZUP’s ENZAMET trial recognised as one of the most important clinical research advances of the past year PATIENTS FROM

1,125 MEN

AUSTRALIA NEW ZEALAND CANADA USA

TOOK PART IN THE STUDY

IRELAND UK

GLOBAL SITES

On World Cancer Day, Tuesday 4 February 2020, the American Society of Clinical Oncology, Inc. (ASCO) released its Clinical Cancer Advances 2020: ASCO’s Annual Report on Progress Against Cancer. This report highlights the most important clinical research advances of the past year and identifies priority areas where ASCO believes research efforts should be focused moving forward. ANZUP’s ENZAMET study, “Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer,” has been selected for inclusion in this year’s edition. The landmark Australian led clinical trial, ENZAMET, showed that hormone therapy with a drug called enzalutamide can improve the survival of some men with advanced, hormone-sensitive prostate cancer. Findings from the ENZAMET trial, led by ANZUP, showed that men with this sort of cancer who receive enzalutamide with standard treatment have a 33% improvement in survival compared to men receiving standard treatment alone. ANZUP Chair, Professor Ian Davis, said metastatic prostate cancer was still the second-leading cause of cancer death in Australian men after lung cancer.

AFTER 3 YEARS

33%

OF MEN COULD LIVE A LONGER LIFE 80%

OF MEN WHO RECEIVED ENZALUTAMIDE AND HORMONE TREATMENT WERE ALIVE

72%

OF MEN WHO RECEIVED STANDARD TREATMENT WERE ALIVE

“The benefits of enzalutamide had already been established for prostate cancers that are no longer responding to hormonal therapy. ENZAMET showed that adding enzalutamide to standard treatment for men starting hormonal therapy for prostate cancer led to a 33% reduction in the chance of dying of prostate cancer, and a 60% improvement in the time it takes to detect the cancer growing again. These results were much better than we thought they might be when we started the trial. Prostate cancer is complex and so are the benefits, side effects and risks of multiple treatments. Clinical trials are the most effective way of determining which treatments, alone or in combination, will provide the greatest survival benefit to the patient with the least adverse outcomes.” Professor Christopher Sweeney, co-chair with Professor Ian Davis of the ENZAMET trial, said, “Inclusion in ASCO’s Annual Report is testament to the fact that this is one of the most significant findings yet in clinical trials for men with metastatic hormone-sensitive prostate cancer – and a great example of effective international collaboration.”

A LITTLE BELOW THE BELT 29

ANZUP trials - prostate

ANZUP are currently running a number of prostate cancer trials. For more details information about these trials, go to the ANZUP prostate cancer trials web page: https://anzup.org.au/content.aspx?page=trials-prostate

ENZA-p

Opening soon!

Status: Opening soon! Location: Australia wide Planned sites: 12 Patients recruited: 0 â&#x20AC;˘ Patients required: 160

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Smaller pre-clinical studies have demonstrated synergistic effects by combining Lu-PSMA with enzalutamide. It is possible that Lu-PSMA can prevent early resistance to enzalutamide, extending the time that men benefit from treatment. The ENZA-p clinical trial aims to compare the effectiveness of enzalutamide in combination with LuPSMA, versus enzalutamide alone for the treatment of prostate cancer. This is a randomised study, so half the men in this trial will be randomly allocated to receive Lu-PSMA and enzalutamide, and the other half will be randomly allocated to receive enzalutamide alone. We plan to enrol 160 participants across Australia. https://anzup.org.au/content. aspx?page=prostatecancertrialdetails

ANZUP trials - prostate

DASL-HiCaP Status: Open and recruiting Location: Australia & Internationally Activated sites: 10 Patients recruited: 16 • Patients required: 1100

The purpose of this study is to see if a new tablet drug, darolutamide, combined with the current best treatments, can improve outcomes for men with high risk prostate cancer that has not spread beyond the prostate area. Previous studies have shown promising results for darolutamide preventing disease progression and improving survival for men with advanced prostate cancer. This is a randomised controlled trial, which means that, in addition to best standard treatments, half the participants on the study will receive darolutamide, and the other half will receive placebo. DASL-HiCaP (ANZUP is being led internationally by ANZUP with another exciting opportunity to collaborate with our partners at the NHMRC Clinical Trials Centre, the Canadian Cancer Trials Group, Cancer Trials Ireland (Ireland and UK), and in the US the Memorial Sloan Kettering Cancer Center and Prostate Cancer Clinical Trials Consortium. We plan to enrol 1,100 men from Australia, New Zealand, Canada, the US, Ireland, and the UK. For more information please refer to https://www.anzup. org.au/content.aspx?page=trials-prostate.

Current locations for the DASL-HiCAP trial: AUSTRALIA NSW • Calvary Mater Newcastle • Chris O’Brien Lifehouse • St George Hospital QLD • Icon Cancer Centre-Gold Coast • University Hospital • Princess Alexandra Hospital • Royal Brisbane and Women’s Hospital • Townsville Hospital SA • Ashford Cancer Centre Research WA • Fiona Stanley Hospital TAS • Royal Hobart Hospital

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Co-badged trials - prostate

#UpFrontPSMA Status: Open & recruiting Location: Australia wide Activated sites: 12 Patients recruited: 1 • Patients required: 140

Most prostate cancer cells have a molecule on their surface called prostate cancer specific membrane antigen (PSMA). PSMA can be targeted with Lutetium-177 PSMA (Lu-PSMA), a radioactive drug that kills prostate cancer cells anywhere in the body. This investigational drug is not approved for use in Australia by the Federal Government’s Therapeutic Goods Administration (TGA). It is a new form of treatment that is effective in some patients with metastatic prostate cancer. It is a radioactive substance that, after injection into a vein, attaches to prostate specific membrane antigen (PSMA). The treatment enables delivery of highly targeted radiation to cancer cells. The emitted radiation only travels about 1mm, which means it mainly causes the killing of cancer cells, while avoiding healthy cells, and seems to be well tolerated with few side effects. This is called radionuclide therapy or theranostic therapy. The purpose of this randomised controlled clinical trial is to compare the effectiveness of Lu-PSMA therapy followed by docetaxel chemotherapy versus docetaxel chemotherapy on its own. Previous clinical trials have shown promising activity of Lu-PSMA in treatment of patients with metastatic prostate cancer. Docetaxel is a chemotherapy drug that is approved by the TGA to treat prostate cancer and has been used for many years in the treatment of metastatic prostate cancer. Since Lu-PSMA radiotherapy and docetaxel chemotherapy are both effective in treating metastatic prostate cancer, it is possible that using Lu-PSMA in addition to standard docetaxel chemotherapy at the beginning of the treatment course may improve patient outcomes when compared to treatment with docetaxel alone. A recent phase 2 clinical trial, showed the effectiveness

32 AALITTLE LITTLEBELOW BELOWTHE THEBELT BELT

of Lu-PSMA when used as a last treatment option and helped control disease progression.This study brings the use of Lu-PSMA forward as a first option to patients, with the hope of disease eradication and potential cure. The trial is open and recruiting. For more information please refer to https://anzup.org.au/content. aspx?page=prostatecancertrialdetails Current locations for the #UpfrontPSMA trial: NSW • Royal North Shore Hospital • Liverpool Hospital • St Vincent’s Hospital Sydney • Calvary Mater Newcastle QLD • Royal Brisbane and Women’s Hospital SA • Royal Adelaide Hospital VIC • Peter MacCallum Cancer Centre • Alfred Health • Monash Health • Austin Hospital WA • Fiona Stanley Hospital • Sir Charles Gairdner Hospital

#UpFrontPSMA is funded through the Prostate Cancer Research Alliance (PCRA) – a program jointly funded by the Australian Government and the Movember Foundation (Movember).

Co-badged trials - prostate

NINJA Status: Active & recruiting Location: NSW and VIC Activated sites: 7 Patients recruited: 55 • Patients required: 474

The NINJA clinical trial aims to compare two emerging schedules of radiotherapy in the treatment of intermediate or high risk prostate cancer. Participants will be randomly assigned to one of two radiotherapy schedules as part of this study. In schedule 1 (called Stereotactic Body Radiotherapy) participants will receive 5 radiotherapy treatments over 2 weeks, and in schedule 2, (called Virtual High Dose Rate Boost), participants will receive Stereotactic Body Radiotherapy delivered in 2 treatments over 1 week followed by 12 treatments of conventional external beam radiotherapy over 2 and a half weeks. It is hoped this research will potentially improve the accuracy and quality of radiotherapy treatment in prostate cancer.

This study is being led by the TransTasman Radiation Oncology Group and co-badged with ANZUP. The study is being funded by Cancer Australia, and we acknowledge MDI for providing the study drug.

This study will include 474 men. Currently we have active sites across Australia and New Zealand with 55 patients enrolled.

VIC • Princess Alexandra Hospital • Peter MacCallum Cancer Centre

Current locations for the NINJA trial: NSW • Calvary Mater Newcastle • Illawarra Cancer Care Centre • Liverpool & Campbelltown Hospitals • St George Hospital • Westmead Hospital

This trial is open and recruiting. If you are interested in participating in the trial, please refer to http://anzup.org. au/content.aspx?page=trials-prostate.

AA LITTLE LITTLE BELOW BELOW THE THE BELT BELT 33 33

Spotlight on bladder and urothelial cancer What is bladder cancer? The bladder is a hollow organ in the lower pelvis. It has flexible, muscular walls that can stretch to hold urine and squeeze to send it out of the body. The bladder’s main job is to store urine. Urine is liquid waste made by the 2 kidneys and then carried to the bladder through 2 tubes called ureters. When you urinate, the muscles in the bladder contract, and urine is forced out of the bladder through a tube called the urethra. In addition, the urothelium is a layer of tissue that lines the urethra, bladder, ureters, prostate and renal pelvis. Bladder cancer develops when abnormal cells in the bladder grow and divide in an uncontrolled way. Cancer that begins in the urothelium of the bladder is much more common than cancer that begins in the urothelium of the urethra, ureters, prostate, or renal pelvis.

Types of bladder cancer Bladder cancer takes different forms: • u rothelial carcinoma, formally known as transitional cell carcinoma, is the most common form of bladder cancer (80-90%) and starts in the urothelial cells in the bladder wall’s innermost layer • s quamous cell carcinoma begins in the thin, flat cells that line the bladder • a denocarcinoma is a rare form which starts in mucusproducing cells in the bladder. If you develop bladder cancer in the lining of the bladder it is called superficial bladder cancer. But if the cancer cells spread to the muscle wall of the bladder or even further to other organs or lymph nodes it is called invasive bladder cancer.

The stats Bladder cancer incidence rate for Australian men is almost 4 times that of women. Bladder cancer was the 9th most commonly diagnosed cancer in Australia in 2019. In 2020, it is estimated 3098 cases of bladder cancer will be diagnosed in Australia. This is equivalent to an estimated incidence rate of 9.6 cases per 100,000 persons. In addition, it is estimated there will be 1016 deaths in Australia from bladder cancer but from 2012 – 2016 on average, 54.3% of people diagnosed with bladder cancer survived 5 years after diagnosis.*

Bladder cancer is common in people aged over 60 and is significantly more common in men than in women.

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Spotlight on bladder and urothelial cancer Bladder cancer symptoms The most common symptom of bladder cancer is blood in the urine (haematuria), which usually occurs suddenly and is generally not painful. Other less common symptoms include: • Problems emptying the bladder; • A burning feeling when passing urine; • Need to pass urine often; • Back pain or lower abdominal pain.

Causes of bladder and urothelial cancer Some factors that can increase your risk of bladder and urothelial cancer include: • smoking; • diabetes; • family history; • w orkplace exposure to certain chemicals used in dyeing in the textile, petrochemical and rubber industries; • use of the chemotherapy drug cyclophosphamide; • chronic inflammation of the bladder.

Common treatment approaches Many times, the best option might include more than one of type of treatment. Surgery, alone or with other treatments, is used to treat most bladder cancers. Early-stage bladder cancers can often be removed. But a major concern in people with early-stage bladder cancer is that new cancers often form in other parts of the bladder over time. Taking out the entire bladder (called radical cystectomy) is one way to avoid this, but it causes major side effects. If the entire bladder is not removed, other treatments may be used to try to

reduce the risk of new cancers. Whether or not other treatments are given, close follow-up is needed to watch for signs of new cancers in the bladder. Depending on the stage of the cancer and other factors, treatment options can include: Bladder cancer surgery – type of surgery done depends on the stage of the cancer. Intravesical therapy – the doctor puts a liquid drug right into your bladder rather than giving it by mouth or injecting it into your blood. Chemotherapy – it can be given in 2 different ways, either straight into the bladder or given in pill form or injected into a vein or muscle. The drugs then go into the bloodstream and travel throughout the body. Radiation therapy – uses high-energy radiation to kill cancer cells. Immunotherapy – is the use of medicines to help a person’s own immune system recognise and destroy cancer cells. Targeted therapy – as researchers have learned more about the changes inside cells that cause cancer, they have developed newer drugs that target some of these changes. These targeted drugs work differently from other types of treatment, such as chemotherapy, and they may work in some cases when other treatments don’t. Clinical trials – several ground-breaking bladder cancer trials using some of the therapies listed above, are currently underway in Australia. You can read more on pg 38. Among Australia’s 15 most common cancers, bladder cancer remains the only one with survival rates that have worsened over the past 30 years. This can mainly be attributed to Australia’s ageing population as the percentage of patients diagnosed with bladder cancer over the age of 80 years has gradually increased. However, if there was not a delay presenting to the doctor, then early identification and referral can lead to timely diagnosis. In addition, the hope is that novel approaches are identified through clinical trials that will help reverse the trend of deteriorating survival rates in bladder cancer.

* https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/summary

A LITTLE BELOW THE BELT 35

Patient power – Melissa Le Mesurier Melissa Le Mesurier joined the ANZUP Consumer Advisory Panel (CAP) in 2019 bringing a wealth of knowledge in corporate communications and PR.

MM trial would be beneficial and help reduce the likelihood of the bladder cancer returning. What has your experience of the trial been like?

Melissa is passionate about medical research, consumer engagement and patient empowerment (personally and professionally), which was sparked when her (now adult) son was diagnosed with cystic fibrosis in 1996 and strengthened when she was diagnosed with bladder cancer in 2017. Melissa talks about her experience with bladder cancer and what events led up to her diagnosis. As well as her drive to empower patients and the community through engagement, education and raising awareness. How did you discover you had bladder cancer? Almost by accident! I was preparing to undergo bowel surgery (not cancer-related) and as part of the work up I was sent to a urologist to investigate some other minor symptoms. A cystoscopy revealed a small but high grade transitional cell carcinoma (TCC). How did you go through the decision making process with your specialist when discussing your treatment options? I researched all I could from reputable sources online but really it came down to trusting my urologist, Professor Shomik Sengupta and being confident in the treatment he proposed.

As the original tumour was only 4mm in diameter, sometimes the length of the treatment (12 months in total) felt like a bit of overkill as I did have a few side effects (mainly tiredness and aches) which were cumulative and lasted long after treatment finished. At the outset of this journey, I had a fairly demanding job which involved lots of commuting so I was very tired by mid-year and eventually resigned from my job. I also had to recover from the bowel surgery which took place at the end of the year, so for the first time in 40 years I stopped work so I could focus on my health. It was a big adjustment but also a welcome relief. What advice would you give other people in a similar situation? Do consider all options, especially clinical trials, when faced with a cancer diagnosis. Do your research and if possible talk to other people who have been down the same path, either in person or via reputable forums online. Ask a lot of questions, get a second opinion if you need to, and make sure you feel you have a good relationship with your specialist – you are literally trusting them with your life.

As the tumour was not muscle invasive I had day surgery (transurethral resection of bladder tumour TURBT) to remove the tumour shortly after diagnosis and then six weeks of initial BCG treatment.

And most of all, if you can afford to, give yourself the time and space to heal both mentally and physically. I became a firm believer in the power of an afternoon nap!

Who suggested the trial for you?

What was your experience with your doctor, nurses, trial liaison like during the trial?

Prof Sengupta mentioned the trial involving a follow up treatment where BCG is used in conjunction with mitomycin.

The way the actual trial was conducted was very professional, from the consent process to the contact I had with my two trial coordinators. The staff at the Epworth Hospital at Richmond where I had my regular ‘instillations’ were terrific and always dealing with the same team, even down to having Prof Sengupta and the same anaesthetist doing each of my six check cystoscopies to date, meant I knew what to expect at every point and that was comforting.

What convinced you to go on to the trial? In retrospect I probably didn’t need too much convincing. Due to my long involvement supporting medical research into cystic fibrosis, I was familiar with the concept of a trial and I trusted my urologist that the BCG+ MELISSA WITH HER SON BEN.

36 A LITTLE BELOW THE BELT

What helped keep your spirits up and gave you support during this period? I didn’t tell too many people beyond family and close friends what I was going through as I found dealing with other people’s reactions and emotions much harder than dealing with my own. I still laugh when I think of one person’s reaction when I told them I had bladder cancer and she said “Is that even a thing?” Clearly it is not a very high profile disease and even less so for women, so a bit of work to do on the PR side! I always tried to see the lighter side of what can be quite an invasive and personal procedure as the BCG+MM instillation. I remember once I dozed off after my procedure and awoke to the sounds of a harp playing – I was very relieved to be told there actually was a harpist playing in the ward foyer and that I hadn’t gone to heaven before my time! We are delighted to have you join the ANZUP CAP. How did find out about the ANZUP CAP? I think Professor Sengupta told me he had nominated me and I agreed while I was still woozy from a general anaesthetic! But seriously, I looked into ANZUP, and I was very impressed in how integrated and valued the consumer reps were. I’ve been involved in some other organisations in this capacity and I’ve felt the involvement was a bit tokenistic and ‘tick a box’. I think ANZUP really are top shelf in this respect and would urge anyone to get involved. Your views as a patient are respected and the other CAP members, along with the whole of ANZUP, were very welcoming when I first met them at last year’s ASM. What are you hoping to contribute to the ANZUP CAP? I’m very happy to lend my professional experience in communications and media to such a worthwhile organisation as ANZUP. A few weeks ago I helped get some publicity on the shortage of BCG for bladder

MELISSA WITH HER HUSBAND CHRIS ENJOYING OAKS DAY AT FLEMINGTON RACECOURSE LAST YEAR.

cancer patients and Professor Dickon Hayne got some on air time with the ABC’s Doctor Norman Swan which was good. That said, I’m sure I’ll gain more than I give being part of the CAP. It has already helped me meet other like-minded patients and learn more about the many great advances our clinicians keep making through medical research and trials.

What three things would you tell a person who just yesterday learned of their cancer diagnosis? 1. D o your homework – about your condition, the doctors that treat you and the treatment and drugs you are prescribed – and ask questions in safe forums. o what gives you the best chance of recovery 2. D – not just complying with treatment, but looking after your physical and mental health and rest up when needed! 3. I f I ever get around to finishing it, buy the book I’ve started writing. It’s tentatively called ‘Patient Power – what to do when the sh*t hits the fan’! It contains a few tips for those newly-diagnosed and how to navigate the health system. I worked in health, as well as having been a carer and a patient, and I truly believe being proactive about your treatment for cancer (or any other disease) can make a big difference.

To find out more about the ANZUP BCG + MM trial go to page 38. If you or your family would like to know more about ANZUP led clinical trials, please discuss with your GP or specialist. MELISSA CYCLING AROUND LAKE BLED IN SLOVENIA

A LITTLE BELOW THE BELT 37

ANZUP trials - bladder

ANZUP are currently running a number of bladder cancer trials. For more details information about these trials, go to the ANZUP bladder cancer trials web page: http://bit.ly/ANZUPbladder

BCG+MM Status: Active & recruiting Location: Australia Activated sites: 14 Patients recruited: 274 Patients required: Stage one: 130 / Stage two: 370

Non-muscle invasive bladder cancer is common and causes substantial suffering. It requires removal or irradiation of the bladder within five years in more than 30% of people with high-risk tumours, despite best current treatment. Recent preliminary studies show promising results from adding mitomycin (MM), a chemotherapy drug, to current treatment with BCG (Bacillus Calmette-Guérin, a strain of modified bacteria which stimulates an immune response to early cancer cells). This randomised trial will determine the effects of adding mitomycin on cure rates, survival, side effects and quality of life. This could potentially provide a simple and costeffective treatment for patients who suffer from this cancer. This study is currently active and recruiting. Please speak with your doctor if this is of interest to you or someone you know. ANZUP collaborates with the University of Sydney through the National Health and Medical Research Council Clinical Trials Centre (NHMRC CTC).

This ANZUP investigator-initiated study is being funded by Cancer Australia and the National Health and Medical Research Council. We acknowledge Omegapharm and Merck Sharp & Dohme for providing the study drugs. Current site locations for the BCG + MM trial are: NSW • Concord Repatriation General Hospital • John Hunter Hospital • Northern Cancer Institute, St Leonards • SAN Clinical Trials Unit • Southside Cancer Care Centre • The Tweed Hospital • Westmead Hospital VIC • The Alfred Hospital • Austin Hospital • Epworth HealthCare (Richmond) • Footscray Hospital • Frankston Hospital • Royal Melbourne Hospital WA • Fiona Stanley Hospital

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ANZUP trials - bladder

PCR MIB Status: Active & recruiting Location: Australia wide Activated sites: 6 Patients recruited: 20 • Patients required: 30

Opened in mid-2016, this trial is aimed at managing bladder cancer that has spread into the wall of the bladder. A combination of chemotherapy and radiotherapy is the current standard treatment. This study aims to assess if it is safe and effective to add an additional new drug called pembrolizumab to the standard therapy of chemotherapy and radiation therapy. Pembrolizumab is a new treatment that “takes the brakes off” the immune system, allowing it to attack cancers more effectively. Studies of pembrolizumab in widespread bladder cancer have shown benefit, with cancer shrinkage observed in about two thirds of people, and in some cases long periods of disease control. At present, pembrolizumab, is approved for use in Australia for the treatment of advanced melanoma in adults. This study is currently active and recruiting. Please speak with your doctor if this is of interest to you or someone you know. We thank and acknowledge MSD for their funding and product support.

Current site locations for the PCR MIB ANZUP clinical trial: NSW • Chris O’Brien Lifehouse • Liverpool Hospital • Prince of Wales Hospital • Royal North Shore Hospital VIC • Austin Hospital WA • Sir Charles Gairdner Hospital

Participation in cancer trials is voluntary & patients can withdraw from a study at any time

If a clinical trial proves that a treatment is more effective than existing options, it may become the new standard of care for patients in the future.

A LITTLE BELOW THE BELT 39

Co-badged trials - bladder

NMIBC-SI Evaluation Status: Active & recruiting Location: Australia, New Zealand and Internationally Activated sites: 18 Patients enrolled Field test 1: 220 (closed - completed) • Patients enrolled Field test 2: 263

Non-muscle invasive bladder cancer (NMIBC) makes up approximately 70-80% of all bladder cancer diagnoses. NMIBC is bladder cancer that has not yet invaded through the wall of the bladder. Treatment is generally intended to reduce the risk of the bladder cancer recurring or progressing to muscle invasive disease. Treatment involves endoscopic resection to the bladder tumours followed by potential intravesical chemotherapy or immunotherapy. Although treatments can significantly reduce the risk of recurrence and progression, there are both benefits and harms that are likely to vary between treatment options. However, little is known about the impact of these treatments on patients’ quality of life. This project follows on from Phase I, which involved qualitative research to develop a draft Non-Muscle Invasive Bladder Cancer Symptom Index (NMIBC-SI). The aim of the current project is to evaluate the psychometric properties of the NMIBC-SI. This will be conducted across two field tests: •F ield Test 1 is a cross-sectional study design asking participants to complete the draft NMIBC-SI questionnaire either on paper or electronically. The purpose of Field Test 1 is to produce a shorter version of the NMIBC-SI by eliminating items with poor psychometric properties. •F ield Test 2 uses a prospective longitudinal study design to evaluate the clinical validity of the final version of the NMIBC-SI. Participants will be asked to complete the NMIBC-SI along with comparative questionnaires at different time-points during their treatment. The purpose of Field Test 2 is to assess the reliability, validity and responsiveness of the final version of the NMIBC-SI to ensure it is fit for purpose in clinical research. ANZUP is currently running this trial in collaboration with Cancer Australia and Cancer Council NSW. This study is being sponsored by the University of Sydney.

40 A LITTLE BELOW THE BELT

This study is currently active and recruiting. Please speak with your doctor if this is of interest to you or someone you know. The NMIBC-SI trial is currently being run at the following sites: NSW • Concord Hospital • Riverina Cancer Care Centre • The Urological Centre • Westmead Hospital QLD • Mater Hospital Brisbane VIC • The Alfred • Austin Health • Eastern Health • Monash Medical Centre • Royal Melbourne Hospital

A co-badged trial is when two (or more) research groups are working together to run a clinical trial.

WA • Fiona Stanley Hospital Canada • University of British Columbia New Zealand • Canterbury Urology Research Trust • Tauranga Urology Research Ltd UK • Salford Hospital USA • Mayo Clinic • University of Minnesota Hospital • University of Kansas

Spotlight on testicular cancer The testicles are two oval glands that sit behind the penis in a pouch of skin called the scrotum. They are part of the male reproductive system and are also called testes (or a testis, if referring to one).

900+

diagnoses

deaths

in Australia each year

will result from testicular cancer in 2020

What is testicular cancer?

Testicular cancer symptoms

Testicular cancer occurs in the testicles (testes). The testicles produce male sex hormones and sperm for reproduction.

Testicular cancer may cause no symptoms. The most common symptom is a painless swelling or a lump in a testicle.

Compared with other types of cancer, testicular cancer is rare. But testicular cancer is the second most common cancer in young men (aged 18 to 39). However, this form of cancer is highly treatable, even when cancer has spread beyond the testicle.

Less common symptoms include:

It is estimated only 928 men will be diagnosed with testicular cancer in Australia in 2020. This equates to 1% of all cancers in men. For Australian men, the risk of being diagnosed with testicular cancer by the age of 85 is 1 in 189. The rate of men diagnosed with testicular cancer has grown by more than 50% over the past 30 years, however the reason for this is not known. Germ cell tumours are the most common testicular cancers. Under a microscope there are two main types that are quite different when observed – seminoma and non-seminoma cells. Seminoma usually occurs in men aged 25-45 but can also occur in men over the age of 60. This form of testicular cancer develops more slowly than non-seminoma cancers. The faster developing, rarer form, of testicular cancer occurs in younger men in their late teens and early 20s. The five-year survival rate for men diagnosed with testicular cancer is close to 97.2%. And in 2019 a total of 30 deaths from testicular cancer were estimated.

• Feeling of heaviness in the scrotum; • Swelling or lump in the testicle; • Change in the size or shape of the testicle; • Feeling of unevenness; • P ain or ache in the lower abdomen, the testicle or scrotum; • Back pain; • E nlargement or tenderness of the breast tissue (due to hormones created by cancer cells).

18-39 years

second most common form of cancer diagnosed in this age group of men (in Australia).

A LITTLE BELOW THE BELT 41

Spotlight on testicular cancer Causes of testicular cancer

Testicular cancer clinical trials

An undescended testicle as an infant, or family history (that is, having a father or brother who has had testicular cancer), are some of the factors that may increase a manâ&#x20AC;&#x2122;s risk of testicular cancer. There is no known link between testicular cancer and injury to the testicles, hot baths, wearing tight clothes or sporting strains.

Testicular cancer treatment Treatment for testicular cancer depends on the type of cancer you have and how far it has spread. Anyone with suspected testicular cancer will need the affected testicle surgically removed in an operation called an orchidectomy. A laboratory will then examine the tissue to confirm the type of cancer and the stage it is at.

Several decades ago testicular cancer was a disease with a very poor prognosis. But now, because of new treatments, tested carefully in clinical trials, it is almost always curable even when it has spread. However, even though there are excellent treatments available, we still need to do better. This can only happen through understanding the science and by performing clinical trials to see which treatments are the ones most likely to help further improve outcomes. ANZUP is involved in clinical trials in testicular cancer through its clinical trials program. Speak with your doctor if you would like to know more about testicular cancer clinical trials and also read about ANZUPs trials on page 44.

After the surgery, you may not need any further treatment but you will be closely monitored. Some men will have chemotherapy or radiotherapy to kill any cancer cells that may have spread to other parts of the body. Others may need further surgery.

References https://www.cancer.org.au/about-cancer/types-of-cancer/testicular-cancer.html https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/cancer-summary-data-visualisation

42 A LITTLE BELOW THE BELT

Joe Bakhmoutski – Cancer treatment in a time of uncertainty I first found out about coronavirus from my oncologist. He rushed in from the airport that morning for our regular check-up. Relieved that I was still cancer free, I asked him about the trip, and he described the panic at the airport, the rate of replication, and what that might mean for all of us. In a matter of days, the virus has taken hold of our world. Infections spiked, and there were reports of more people dying. The supermarket shelves were swiped clean. It did not sink in until a bright yellow and black sign went up for the testing clinic. Those worrying thoughts are inevitable, and yet, you might be much better prepared for it if you have been touched by cancer... In a way, you were forced to live with worry, and find ways around it! It comes at you in unexpected ways. When I was waiting on my test results after treatment, I got so tense with frustration and worry, I had to get out of the house. It was pitch dark, and I was walking along the railway tracks, and I could not stop thinking: What if the cancer is still there, inside me? Is it growing, has it spread? Is there another treatment? Or is this it, am I going to die? Well, what can I do about cancer being there, or not? It’s not up to me - it’s all biology and random chance... But what about the rest of my life? Do I have the rest of my life under control? Am I doing what I can to enjoy life, to stay connected with people I care about, to be the best person I can be?

How can I make a greater impact? How can I form even stronger bonds with people I care about? How do I bring more joy and vibrancy into my life? I started making changes – spending more time playing silly games with my son, working on the podcast to support folks touched by cancer, going for nightly walks... Calm has started to come back into my life because I spent less time worrying about how things might turn out and more time and energy into things that were important to me, and people I care about the most. So when I get close to the time of my regular check-up, or when I read about the uncontrolled spread of COVID-19, I ask myself – have I been living my best life? I now call it the 3P’s – People, Projects and Passions, as a way to check in with how I am going: People – who is the one person who looks up to you right now who might need your support and encouragement? Could you text this person, or jump on a video call with them? Projects – what is the one project that I can plan from start to finish that will give me a sense of achievement? Passions – what is the one hobby or passion you love doing but maybe haven’t had the time for that you could do now? Can you do it from your own home? Can you get your friends, family, or colleagues involved to support you in what you want to do?

This is a tough time, but you can get through this, and have the life you deserve despite the uncertainty!

Because when you are living your best life, when you are taking control of things that you can influence in some way, then you have the power to deal with the uncertainty. This is when you can manage worry about the virus, about cancer because it’s only one part of a bigger life that you’re living. Then I thought – I am NOT living my best life, in a way that works for me...

JOE WITH HIS ONCOLO GIST DAVID AT ANZUP’ POOK S BELOW TH E BELT PED IN MELBOUR ALTHON NE

For more about Joe and Simplify Cancer Podcast go to: simplifycancer.com

HIS JOE AND

FAMILY

A LITTLE BELOW THE BELT 43

ANZUP trials - testicular

ANZUP are currently running a number of testicular cancer trials. For more detailed information about these trials, go to the ANZUP testicular cancer trials web page: https://anzup.org.au/content.aspx?page=trials-testicular

TIGER Status: Active & recruiting Location: Australia wide & Internationally Activated sites: 4 (Australia) Patients recruited: 6 • Patients required: 60 + 420 internationally

This randomised phase III trial will study how well standard-dose combination chemotherapy works compared to high-dose combination chemotherapy and stem cell transplant in treating patients with germ cell tumours that have returned after a period of improvement or did not respond to treatment. Drugs used in chemotherapy, such as paclitaxel, ifosfamide, cisplatin, carboplatin, and etoposide, work in different ways to stop the growth of tumour cells. They either kill the cells by stopping them from dividing or stop them from spreading. Giving chemotherapy before a stem cell transplant halts the growth of cancer cells by stopping them from dividing or by killing them. Giving colony-stimulating factors, such as filgrastim or pegfilgrastim, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy is then given to prepare the bone marrow for stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. It is not yet known whether high-dose combination chemotherapy and stem cell transplant are more effective than standard-dose combination chemotherapy in treating patients with refractory or relapsed germ cell tumours.

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Up to 420 patients will be enrolled in Australia, New Zealand and other countries. Currently we have 7 patients enrolled and 4 sites open in Australia. This study is currently active and recruiting. Please speak with your doctor if this is of interest to you or someone you know. ANZUP is collaborating with the Alliance for Clinical Trials in Oncology (USA) and EORTC (Europe) and the NHMRC Clinical Trials Centre. We thank and acknowledge the Movember Foundation for their funding support to conduct the TIGER trial. For more information, please go to the trials page on the ANZUP website: https://www.anzup.org.au/content. aspx?page=testicularcancertrialdetails. Current site locations for the TIGER trial are: NSW • Chris O’Brien Lifehouse VIC • Eastern Health • Peter MacCallum Cancer Centre QLD • Princess Alexandra Hospital

ANZUP trials - testicular

P3BEP Status: Active & recruiting Location: Australia wide & Internationally Activated sites: 56 Patients recruited: 129 • Patients required: Stage 1 (150) Stage 2 (350)

The current standard practice for the treatment of germ cell tumours is the use of the chemotherapy combination called BEP, which consists of three chemotherapy agents – Bleomycin, Etoposide and Cisplatin – administered on a three-weekly cycle. BEP is given with a drug called pegylated G-CSF (or pegfilgrastim) that stimulates white blood cell production. The purpose of this study is to determine whether giving the same dose of BEP on a two-weekly schedule will be more effective and better tolerated than a three-weekly schedule. The two-weekly schedule is called “accelerated BEP” and the three-weekly schedule is called “standard BEP”. Up to 500 patients will be enrolled in the study in Australia, New Zealand and other countries. Currently we have 54 sites open in Australia and New Zealand, and 129 patients enrolled. We have also set up the trial in the US, in Ireland with the support of Cancer Trials Ireland and the Medical Research Council, Cambridge University, UK. This study is currently active and recruiting. Please speak with your doctor if this is of interest to you or someone you know. For more information, please go to the trials page on the ANZUP website: https://anzup.org.au/ aspx?page=testicularcancertrialdetails ANZUP collaborates with the University of Sydney through the NHMRC CTC to conduct P3BEP Trial.

This ANZUP investigator initiated study is being funded by a Cancer Australia grant. Current locations for the P3BEP trial: NSW • Princes of Wales • Calvary Mater Newcastle • Chris O’Brien Lifehouse • C oncord Repatriation General Hospital • Macquarie Cancer Clinical Trial • Nepean Hospital QLD • Princess Alexandra • Royal Brisbane & Womens Hospital VIC • Austin Health • Border Medical Oncology • Eastern Health • Peter MacCallum Cancer Centre SA • Flinders Medical Centre • Royal Adelaide Hospital WA • Fiona Stanley Hospital TAS • Royal Hobart Hospital NEW ZEALAND • Auckland Hospital • Christchurch Hospital • Palmerston North Hospital • Starship Hospital –Paediatric UK • Royal Preston Hospital • B eatson West of Scotland Cancer Centre • B ristol University Hospital • V elindre Hospital • C ambridge University Hospital Paediatric

• • • • • • •

niversity Hospital Southampton U R oyal Marsden Hospital t James Hospital - Leeds S S t Bartholomews Hospital ottingham University Hospital N elfast City Hospital B D erriford Hospital, Plymouth

USA • W ashington University School of Medicine • R ady Children’s Hospital • A ugusta University Medical Centre • Vanderbilt University Medical Centre • L ucile Packard Children’s Hospital Stanford • M emorial Health University Medical Centre • U niversity of Mississippi Medical Centre • G eisinger Medical Center • P almetto Health Richland • M ethodist Children’s Hospital of South Texas • U niversity of Wisconsin Hospital ast Tennessee Children’s Hospital • E • M iller Children’s and Women’s Hospital Long Beach • R oswell Park Cancer Center • U SC / Norris Comprehensive Cancer Care • B roward HealthCare • D ana Farber Cancer Center • U T Southwestern Simmons Cancer Center • L A Biomedical Research Institute at Harbor- UCLA • D ayton Children’s Hospital • U niversity of Texas Science Center at San Antonio ayo Clinic • M • A dvocate Children’s Hospital – Oak Lawn • C arolinas Medical Center

AA LITTLE LITTLE BELOW BELOW THE THE BELT BELT 45 45

Spotlight on kidney cancer The kidneys are essential organs that filter the blood. These two bean-shaped organs, each about the size of a fist, remove waste products through the urinary tract. One of the waste products is urine and like any other organ, the kidney can be affected by cancer.

What is kidney cancer?

risk does increase with age. Also, men are almost twice as likely to be diagnosed with kidney cancer as women.

Kidney cancer can be subdivided into several different types, based on the appearance of the cancer cells under a microscope as well as other genetic factors.

In 2020, it is estimated there will be 917 deaths from kidney cancer (616 males, 301 females) and the fiveyear survival rate for Australians diagnosed with kidney cancer is 78.5%, although most people with kidney cancer localised only to the kidney can be cured.

The type of kidney cancer is not usually important with regard to surgery, but can be very important if more treatment is needed. Kidney cancer starts in the cells of the kidney. About 90% of kidney cancers are renal cell carcinomas (RCC). Usually only one kidney is affected but, in rare cases, the cancer may develop in both. Other less common types of kidney cancer include: • U rothelial carcinoma which can begin in the ureter or renal pelvis where the kidney and ureter meet. It is generally treated like bladder cancer. • W ilms tumour, which is the most common type of kidney cancer in younger children. Kidney cancer has become increasingly more commonly diagnosed and survival rates continue to improve. This cancer is the 7th most diagnosed cancer in Australia and in 2020 it is estimated there will be 4,193 new cases of kidney cancer diagnosed (2,755 males and 1,438 females). Kidney cancer is rare in people under 40 but

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Kidney cancer symptoms Most people with kidney cancer have no symptoms. Many are diagnosed with the disease when they see a doctor for a different reason. Symptoms may include: • blood in the urine (haematuria); • pain or a dull ache in the side or lower back that is not due to an injury; • a lump in the abdomen; • rapid, unexplained weight loss; • constant tiredness; • fever not caused by a cold or flu. If you are experiencing some of these symptoms, please see your doctor.

Spotlight on kidney cancer 4,000+

2.8%

in Australia each year

of all newly diagnosed cancers in Australia

diagnoses

men are almost twice as likely to be diagnosed

Causes of kidney cancer

Treatment options

The causes of kidney cancer are not known, but factors that put some people at higher risk include:

Treatment will depend on the type of kidney cancer, the stage of the cancer and your general health. The main treatment for kidney cancer is surgery alone or with radiotherapy and will depend on the stage of the cancer. All treatment has benefits and side effects, which need to be discussed with your cancer care team.

• Obesity – Excess body fat may alter certain hormones that can lead to kidney cancer. • Smoking – Up to one-third of all kidney cancers are thought to be related to smoking. People who smoke have almost twice the risk of developing kidney cancer as non-smokers. • High blood pressure – Whether it is caused by another medical condition or due to being overweight, high blood pressure increases the risk of kidney cancer. • K idney failure – People with end-stage kidney disease have an increased risk of developing kidney cancer. • Family history – People who have family members with kidney cancer, especially a sibling, are at a greater risk. • I nherited conditions – About 3–5% of kidney cancers occur in people with particular inherited syndromes, such as von Hippel-Lindau disease, Birt-Hogg-Dubé syndrome, and hereditary papillary RCC. • E xposure to toxic substances at work – After regular exposure to certain chemicals, such as arsenic, cadmium or some metal degreasers, the risk of kidney cancer may be higher.

Treatment for kidney cancer is provided by a multidisciplinary team, comprising a group of doctors and other health professionals with expertise in kidney cancer. This team will regularly meet and discuss the patient’s medical history, organise appropriate tests, assess the test results, and together determine the most appropriate treatment care plan.

Clinical trials One treatment option is taking part in a clinical trial. A trial will help confirm whether novel medicines are safe and effective to introduce as new treatment for kidney cancer. During a trial your health and progress is monitored extremely closely and as a participant in a trial you may also gain access to a treatment option that is not yet available to the wider public. If you have already had one or more forms of cancer treatment and are looking for a new treatment option, there are clinical trials for you to think about. Or, if you’ve just found out you have cancer, the time to think about joining a trial is before you have any treatment. Read more about the ANZUP kidney cancer trials on page 50.

Reference: https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/cancer-summary-data-visualisation

A LITTLE BELOW THE BELT 47

The SORCE Trial – then and now Between July 2007 and April 2013 over 1700 patients were randomised on a trial that was hopefully going to answer questions about how to treat people with kidney cancer, also known as renal cell carcinoma (RCC). Now, over 12 years later, the trial, called the SORCE trial, has closed and provided information on treatment options for kidney cancer patients in the future.

What was the SORCE trial? Currently, after surgery to remove all visible kidney cancer, there are no treatments with proven benefit. So the standard and best approach is to monitor patients closely to check for signs of kidney cancer returning. The SORCE trial was established to see whether a drug called sorafenib could reduce the chance of kidney cancer coming back once it has been completely removed by surgery. The trial also wanted to explore if sorafenib would help patients live longer. There were 1711 patients who took part in the trial from 147 sites in the UK, Australia, France, Belgium, Denmark, The Netherlands and Spain. The trial participants were divided into three groups:

PLACEBO 3 YRS

Group A: received a placebo (non-active) tablet and three years of observation.

Group B: received one year of sorafenib and two years of observation.

SORAFENIB

SORAFENIB 1 YR

Group C: received three years of sorafenib.

3 YRS

Patients in group A were not at a disadvantage as they were essentially receiving the same treatment they would have received outside of the SORCE trial. SORCE is what is called a double-blind trial - for every 8 patients allocated, 2 received arm A, 3 received arm B and 3 received arm C. Neither patients nor their doctors knew which treatment each patient received.

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Who took part in the SORCE Trial? SORCE trial patients had: • No signs of disease after surgery to remove their kidney cancer • An intermediate or high risk of their cancer coming back • No previous anti-cancer treatment other than their surgery

The results After following the 1711 patients over the course of 12 years, enough information was gathered and analysed to confirm the results found. In addition, the results were also consistent with other trials that investigated sorafenib or similar agents. Many patients stopped treatment early, mostly due to the side effects of sorafenib treatment. And overall it was found there was no benefit for treatment with sorafenib, whether it was given for one year or three years. Therefore, sorafenib will not be used to treat patients who have had their kidney cancer removed by surgery. Careful observation with regular clinical reviews, imaging and blood tests will remain the best care for patients following surgery to remove kidney cancer.

Will these results make a difference? Even though it turned out sorafenib did not improve results for kidney cancer patients, the SORCE trial has produced a great deal of scientific information which will be used for future research. This information would not have been gathered without clinical trial participation. The results mean clinical trials will continue so a treatment that prevents kidney cancer returning after surgery can be found. The hope is that future patients will help make important discoveries that will ultimately help others, even if that discovery demonstrates that a promising treatment is shown not to work.

SORCE Trial – a participant’s perspective A sore left shoulder blade led one of ANZUP’s Consumer Advisory Board members, Les Land, to the general practitioner back in early 2010. Les was referred to a urologist who undertook a CT scan and biopsies 6 months apart. The diagnosis was a cancerous growth on the left kidney – not what was expected when the early presentation was a troubling pain in his shoulder. The surgeon then advised the entire kidney needed to be removed. LES LAND

Following surgery, Les did not know what his treatment options were. He was not aware what was recommended to kidney cancer patients - and this included clinical trials. He actually had no knowledge of clinical trials research prior to his diagnosis and surgery. But following the removal of his kidney, his surgeon suggested he take part in a clinical trial. This trial was the SORCE trial. The trial was going to ascertain if a drug called sorafenib could decrease the chance of kidney cancer returning once it has been completely removed by surgery.

“I started the trial from a selfish point of view knowing they’d look after me extremely well. I thought it was a good idea to take part in the trial as I would be monitored on a regular basis and at the same time help the medical staff gain any relevant information.”

As with most clinical trials, patient monitoring and care is more frequent and Les found this was definitely the case whilst on the SORCE trial - the support team were terrific. At times the trial dosage needed to be altered to overcome some side effects but the support team were always only a phone call away. Les remained on the medication allocated to him for the full 3 years with a few ups and downs along the way. Every 6 months he had blood tests, chest X-rays or whatever the trial protocol required. As the trial progressed and Les found out more about trials in general, he felt he was contributing more than expected. The more involved he got, the more he thought about other people who might be diagnosed just like himself and that perhaps his small contribution would help. Les also now feels more confident suggesting family and friends investigate if there is a trial right for them. His cousin, diagnosed with internal melanoma with a very poor initial diagnosis, has also joined a trial with excellent prospects. Now the SORCE trial has closed and the results have become available, Les can feel confident he has helped the clinical trials team answer important questions about how to treat people with kidney cancer in the future.

“I am glad I took part. The main reason in my view why it is called a trial is to see if it works. Some do, some don’t. By doing more trials I believe the medical profession can use the outcomes to select the correct tests and treatments for patients for better outcomes.”

LES LAND WITH THE CAP

A LITTLE BELOW THE BELT 49

ANZUP trials – kidney

ANZUP are currently running a number of kidney cancer trials. For more details information about these trials, go to the ANZUP kidney cancer trials web page: http://bit.ly/ANZUPkidney

KEYPAD Status: Active & recruiting Location: Australia wide Activated sites: 16

The most common kind of advanced kidney cancer is called clear cell kidney cancer. This trial aims to improve survival rates for people with this cancer.

Patients recruited: 39 • Patients required: 70

Renal cell carcinoma (RCC) is the 7th most diagnosed cancer in Australia and the 14th most common cancer in Western populations. Approximately 90% of kidney cancers are renal cell carcinomas (RCC). At the moment the five-year survival rate for Australians diagnosed with kidney cancer is 78.5%, although most people with kidney cancer localised only to the kidney can be cured.

ANZUP collaborates with the University of Sydney through the NHMRC CTC to conduct the KEYPAD Trial.

Immune therapies have been shown to be effective in about a quarter of patients with clear cell renal cell carcinoma after the standard treatment (sunitinib) has failed.

NSW • Calvary Mater Newcastle • Northern Cancer Institute • Concord Repatriation General Hospital • St George Hospital • Border Medical Oncology Research Unit • St Vincent’s Hospital Sydney

This study will test if denosumab, a drug frequently used to treat osteoporosis, (thinning of the bones), can team up with immune therapy to improve survival and increase the chance of the cancer shrinking for people with clear cell kidney cancer. In the trial, people with advanced clear cell kidney cancer will be offered treatment with two antibodies (a type of protein). This trial will investigate if these drugs taken together can increase the ability of the body’s immune system to attack kidney cancer cells. It is hoped that by combining pembrolizumab with denosumab, will stimulate the immune system, so that the immune therapy will work better in the tumours.

We thank and acknowledge Amgen and MSD for providing product and funding to support our KEYPAD Trial. We are currently running the KEYPAD trial at the following locations:

QLD • Royal Brisbane & Women’s Hospital • S unshine Coast University Hospital • I con Cancer Care • T he Townsville Hospital SA • Flinders Medical Centre VIC • Eastern Health • Monash Health Clayton • Peter MacCallum Cancer Centre • Ballarat Oncology and Haematology Services WA • Fiona Stanley Hospital

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ANZUP trials – kidney

UNICAB Status: Active & recruiting Location: Australia wide Activated sites: 11 Patients recruited: 14 • Patients required: 48

This study aims to find how safe, tolerable and effective a new treatment called cabozantinib is for non-clear cell kidney cancer. All patients will take cabozantinib orally every day, until the medication is no longer effective. There is no placebo (inactive treatment), which means that everyone who takes part in the trial will receive the active cabozantinib drug. Cabozantinib is an anti-cancer drug that works by blocking cancer cell growth. Cabozantinib has previously been used in the treatment of many cancers, including clear cell kidney cancer and thyroid cancer. However, it has not been tested in people with non-clear cell kidney cancer.

Cancer trials can be undertaken in different settings. Depending on the trial, it may occur in a hospital, a clinic or the patient’s home.

We are currently running the UNICAB trial at the following locations: NSW • Border Medical Oncology • Calvary Mater, Newcastle • Campbelltown Hospital • Macquarie University • Northern Cancer Institute • St. George Hospital QLD • Royal Brisbane & Women’s Hospital SA • Adelaide Cancer Centre • Flinders Medical Centre VIC • Monash Medical Centre, Clayton • Eastern Health ANZUP collaborates with the Centre for Biostatistics and Clinical Trials (BaCT)to conduct the UNICAB Trial. We thank and acknowledge Ipsen for providing product and funding to support our UNICAB Trial.

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Spotlight on penile cancer

What is penile cancer?

Penile cancer symptoms

The penis is part of the male reproductive and urinary systems. Penile cancer is a disease in which malignant (cancer) cells form in the tissues of the penis. Most penile cancers are squamous cell carcinomas (cancer that begins in flat cells lining the penis).

Possible signs of penile cancer include sores, discharge, and bleeding.

The stats* Penile cancer is rare. Around 103 men are affected by this cancer per year. In 2020, there is estimated to be 13 cases only of penile cancer diagnosed in persons aged 55-59 years, i.e. 0.8 cases per 100,000 persons. This cancer is more common in men over the age of 55. The mortality rate for penile cancer is 0.1 deaths per 100,000 persons which meant there will be an estimated 24 deaths in Australia in 2020. And between 2012 to 2016, the 5 year survival rate after diagnosis was 73.8%.

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These and other symptoms may be caused by penile cancer. Other conditions may cause the same symptoms. Check with your doctor if you have any of the following problems: â&#x20AC;˘ Redness, irritation, or a sore on the penis â&#x20AC;˘ A lump on the penis

103 men are affected by penile cancer per year in Australia

Spotlight on penile cancer Causes of penile cancer Infection with human papilloma virus is a risk factor for cancer of the penis. Some other conditions that affect the appearance of the skin of the penis can lead to cancer, so it’s important to see your doctor if you notice white, red or scaly patches.

Who treats penile cancer? Based on your treatment options, you might have different doctors of differing specialties on your treatment team. These doctors could include: • A urologist: a surgeon who specialises in diseases of the male genitals and urinary tract • A radiation oncologist: a doctor who uses radiation to treat cancer

Men reported that the impact of penile cancer and its treatments affected physical, psychological, and sexual well-being with each facet impacting and being intertwined with the other at varying degrees.**

• A medical oncologist: a doctor who uses chemotherapy and other medicines to treat cancer • A psychologist trained in sex therapy: a specialist who can help patients and their partners discuss their feelings around intimacy and sexual well-being

Thinking about taking part in a clinical trial

How is penile cancer treated?

Progress in treating penile cancer has been hampered by its rarity. It is difficult to recruit enough patients to penile cancer clinical trials. But clinical trials are carefully controlled research studies that are done to get a closer look at promising new treatments or procedures. Clinical trials are one way to receive stateof-the art cancer treatment, management and care that is not yet available to the wider public. Clinical trials are also the best way for a multidisciplinary team to learn better methods to treat this rare form of cancer.

Surgery is the main treatment for most men with penile cancers, but sometimes radiation therapy may be used, either instead of or in addition to surgery. Other local treatments might also be used for earlystage cancer. Chemotherapy may be given for some larger tumours or if the cancer has spread. As well as the medical treatment for penile cancer it is also important to adjust to living with the diagnosis. A specialist nurse, psychologist, social worker, a GP and support groups can all help and provide ways of coping.

If you would like to learn more about clinical trials that might be right for you, start by asking your doctor or contact ANZUP.

*https://www.aihw.gov.au/reports/cancer/cancer-data-in-australia/contents/summary ** What are the unmet supportive care needs of men and their loved ones affected by penile cancer? A systematic review of the empirical evidence. Presenter and lead: Associate Professor Catherine Paterson https://www.anzup.org.au/docview.aspx?id=1029

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Rare cancers In Australia a ‘Rare Cancer’ is defined as one which has fewer than 6 diagnoses per 100,000 of the population.

Penile cancer

Due to the low number of people with these cancers, the amount of research and clinical trials on these disease types are drastically less than those with common cancers.

Penile cancer falls within the rare cancer category. Penile cancer has reported incidence of 1 per 100,000 of the population.

With less research, we have less information about these cancers, there is less community awareness, diagnosis remains slow and treatment availability is limited. All of this adds to the increased mortality rates for rare cancers. The only way we can work to improve the diagnosis and outcomes of these cancers with through increasing the focus on research. The cancer research process is done to find out new ways of diagnosing and treating cancers. Trials can help determine if treatments are safe and effective or better than the standard treatment. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Currently the most common treatment for penile cancer is surgery, although if diagnosed early treatment could be done through less invasive chemotherapy, laser therapy or brachytherapy. ANZUP added penile cancer to its focus in March 2019.

“Penile cancer is a rare but significant male cancer not previously specifically recognised by ANZUP [cancer research] sub-committees and needed a home,” Professor Dickon Hayne, (Chair, ANZUP Bladder, Urothelial and Penile ‘BUP’ Subcommittee.)

Being a rare cancer, it does present a particular challenge for research but ANZUP feels it is incredibly important. The inclusion of penile cancer boosted ANZUP’s disease types to five; prostate, bladder, kidney, testicular and penile cancers. Since that time, ANZUP has been working towards starting a clinical trial for penile cancer. But, there are many steps before a trial can be launched.

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Rare cancers ANZUP member Associate Professor Catherine Paterson has been leading some ground breaking research on the impacts of penile cancer. Her systematic review focused on the supportive needs of penile cancer patients.

The way penile cancer is treated today is based on previous cancer research and trials. This is a small but steady step towards finding a better future for those with the disease. But we know that the way penile cancer is diagnosed and treated can be improved.

Some of the results of Associate Professor Paterson’s study showed that patients had concerns and frustrations due to a lack of doctor’s knowledge and ability to diagnose their cancer. One of the challenges that was highlighted by the study was the requirement to raise the profile of awareness of the early signs and symptoms of penile cancer.

ANZUP is committed to improving the outcomes of people with penile cancer, but we need your help in doing so.

Here are some ways you can help:

“The rarity of penile cancer represents a significant challenge to the patient, partner and healthcare professional from initial diagnosis to treatment and into survivorship.”

• If you have penile cancer, or know someone who has – get in touch with ANZUP today via anzup@anzup.org.au While we don’t have any trials currently for penile cancer, we are always looking for people who are willing to be a part of research. Patients who take part in clinical trials and reaseach help improve the way cancer will be treated in the future. • S hare this article with your networks and your local GP – this will help increase awareness of penile cancer. If you would like more copies, you can view this on our website (https:// www.anzup.org.au/content. aspx?page=newsletter) or you can order more hardcopies via anzup@anzup.org.au

Associate Professor Catherine Paterson

• D onate to ANZUP – ANZUP funds not only cancer trials, but all types of cancer research that aims to improve the lives of those with cancer. Your donation will get us one step closer to

a trial for penile cancer. https://www.anzup.org.au/donate/ donateStep1Details.aspx

A/PROF CATHERINE PATERSON PRESENTING HER STUDY ON PENILE CANCER

Sources: A/Prof Catherine Paterson’s 2019 ANZUP Annual Scientific Meeting presentation https://www.rarecancers.org.au/page/131/what-is-a-rare-cancer

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ANZUP trials in follow up

Trials in follow up Once a clinical trial is finished, researchers scrutinise all the information collected during the course of the study. Reviewing all the data allows researchers to decide whether the results mean the new drug or device should continue to the next phase of clinical trial, or, when applicable, seek approval for broader use by the appropriate authorities. Once a new drug or device has been proven to be effective and safe, it may become part of standard treatment for the condition or disease. Review and analysis of the information can take an extended period of time. So there may be a delay before the results of a clinical trial are known. This is definitely the case with larger trials that can involve thousands of people from many hospitals both in Australia and overseas. In large multi-centre trials, the examination of the data and outcomes may take place over several years. If you have taken part in a trial and specified you wish to know the overall results of the trial, the researchers should make them available to you directly. Usually results of all completed studies will also be made available in papers or reports published in scientific journals. ANZUP now has nine trials in follow-up across 4 of the below the belt cancer types – bladder, testicular, prostate and kidney cancer.

ANZUP Trials 1. BL12 – Bladder Cancer This study was designed to look at whether NabPaclitaxel improves survival and is less toxic, with improved quality of life, compared with Paclitaxel in people with advanced or metastatic urothelial cancer, in the setting where the cancer has grown or come back during or within 12 months of completion of platinum based chemotherapy. Urothelial transitional cell cancer (uTCC) is a type of cancer that typically starts in the cells that line the inside of the urinary system. People with “advanced or metastatic urothelial cancer” have cancer which has spread beyond the region of the urinary system, typically to lymph nodes, the wall of the abdomen or pelvis, bones or other organs. Chemotherapy is commonly used in this situation. Chemotherapy drugs

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of a type called taxanes have commonly been used as a second line treatment. This family of chemotherapy drugs include Nab-Paclitaxel and Paclitaxel. Recruitment to this study ceased on the 7th April 2017 and sites are being closed out. As part of this process, sites are required to submit documents and begin the process of archiving all trial records for 15 years from the end of the trial. And once it becomes available, the final trial publication will be submitted to the Human Research Ethics Committee.

2. ENZAMET – Prostate Cancer Enzalutamide is a new hormone treatment taken as tablets. Previous trials have proven that enzalutamide improves survival and quality of life in men with prostate cancer that has stopped responding to standard hormone treatments and chemotherapy. This large, international randomised trial was undertaken to determine if treatment with enzalutamide can improve survival and quality of life in men starting hormone treatment for newly diagnosed prostate cancer that has spread beyond the prostate. The trial was led from Australia by ANZUP in collaboration with the NHMRC Clinical Trials Centre. It involved 1,125 men from Australia, New Zealand, Canada, the US, Ireland, and the UK. This landmark Australian led clinical trial, ENZAMET, has now shown that hormone therapy with a drug called enzalutamide can improve the survival of some men with advanced, hormone-sensitive prostate cancer. Findings from the ENZAMET trial, led by ANZUP, have shown that men with this sort of cancer who receive enzalutamide with standard treatment have a 33% improvement in survival compared to men receiving standard treatment alone and a 60% improvement in the time it takes to detect the cancer growing again. These results were much better than it was thought they might be when the trial began.

ANZUP trials in follow up

3. ENZARAD – Prostate Cancer

5. TheraP – Prostate Cancer

ENZARAD is a randomised phase 3 trial of enzalutamide in androgen deprivation therapy with radiation therapy for high risk, clinically localised, prostate cancer.

Lutetium-177 PSMA radionuclide therapy (Lu-PSMA) is a new treatment for advanced prostate cancer. Lu-PSMA is a radioactive molecule that specifically attaches to cells with high amounts of PSMA on the surface of the cells. This allows the radioactivity to be delivered mainly to the prostate cancer cells wherever they have spread, while sparing most normal tissues. Previous small studies of Lu-PSMA showed promising activity in patients with advanced prostate cancer.

Enzalutamide is a new hormone treatment taken as tablets. Previous trials have proven that enzalutamide improves survival and quality of life in men with prostate cancer that has stopped responding to standard hormone treatments and chemotherapy. This large, international randomised trial will determine if treatment with enzalutamide can improve survival and quality of life in men starting radiation and hormone therapy for prostate cancer that does not seem to have spread beyond the prostate. The trial has been led from Australia by ANZUP in collaboration with the NHMRC Clinical Trials Centre. The trial accrued 802 men from 69 sites across Australia, New Zealand, Canada, the US, Ireland, and the UK. Recruitment closed on 30th June 2018.

4. Pain Free TRUS B – Prostate Cancer A prostate biopsy involves taking small pieces of the prostate through a needle so that it can be looked at through a microscope. A Trans Rectal Ultrasound (TRUS) guided biopsy is the usual method and involves insertion of a thin needle through the wall of the rectum into the prostate using the guidance of an ultrasound probe. An injection of a local anaesthetic (lignocaine) around the prostate is the standard method of reducing the discomfort of a prostate biopsy. Methoxyflurane (Penthrox®) is a drug given with a simple inhaler and is widely used by first-aid services to reduce pain. This randomised trial will determine if the discomfort of prostate biopsies can be reduced by giving men inhaled methoxyflurane in addition to their standard injections of local anaesthetic. This is a phase 3 double-blind placebo-controlled randomised trial of methoxyflurane with peri prostatic local anaesthesia to reduce the discomfort of trans rectal ultrasound-guided prostate biopsy. This study has accrued a total of 420 participants across Australia and New Zealand and has now completed recruitment.

This randomised study has compared Lu-PSMA, with a type of chemotherapy called cabazitaxel, which is the standard treatment for advanced prostate cancer when other treatments have stopped working. Half the participants received Lu-PSMA and half received cabazitaxel. This trial enrolled 200 participants in Australia. ANZUP was able to report interim results of the TheraP clinical trial at the American Society of Clinical Oncology (ASCO) Annual Scientific Virtual Meeting on Friday 29 May 2020. A favourable response, defined by reduction of PSA by 50% or more, occurred in 66% of men assigned to receive Lu-PSMA compared to 37% with cabazitaxel. Results of the trial also demonstrated the treatment had less severe side effects than chemotherapy. Patient follow-up is ongoing with initial results suggesting the new treatment may delay progression of prostate cancer. TheraP is a partnership between ANZUP Cancer Trials Group and the Prostate Cancer Foundation of Australia (PCFA) with support from the Australian Nuclear Science and Technology Organisation (ANSTO), Endocyte, It’s a Bloke Thing, Movember and CAN4CANCER.

6. U NISON – Kidney Cancer In this clinical trial ANZUP will test whether new immune treatments can help people with rare kidney cancer (‘non-clear cell’ cancer). Non-clear cell kidney cancer represents approximately 25% of people with kidney cancer; and because it is rare there are no treatments currently reimbursed in Australia. The UNISoN trial is now closed to recruitment and is in follow up. This trial is investigating immune treatments

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ANZUP trials in follow up

in two different ways; firstly the trial is investigating how well one immune treatment (nivolumab) works alone. If this is unhelpful by itself, then people can continue taking nivolumab but also add in a 2nd immune treatment (ipilimumab). The trial will also discover how many people will benefit from one drug alone, and by doing detailed laboratory testing of people’s cancer samples, we hope to also learn who will only benefit from taking both treatments together. Nivolumab and ipilimumab have been used alone or together in many cancers, so the side-effects are well known and should be manageable. Immune treatments help some people with cancer, especially those with melanoma, common (clear cell) kidney cancer, lung and bladder cancer. Unfortunately they are much less effective in other cancers (like pancreas, prostate and brain cancers). Nivolumab and ipilimumab have not been tested in people with non-clear cell kidney cancers, so ANZUP is delighted to ask this question, and hopes to help people with this rare disease. We thank and acknowledge BMS for providing the study drug and funding to conduct the UNISoN trial.

Co-badged Trials 7. p roPSMA – Prostate Cancer Prostate cancer is the most commonly diagnosed cancer in Australian men. If detected early, when disease has not spread, there is a high chance of cure. Relapse, however, is not uncommon despite careful selection of patients prior to surgery or radiotherapy. This, in part, reflects a failure to detect disease spread at baseline due to limited accuracy of current scanning techniques. More accurate scanning may improve outcomes by redirecting patients with disease spread from unsuccessful local treatments to more appropriate management. This clinical trial will investigate a new type of scan which provides whole body images of prostate cancer spread. Early experience suggests that this new technology, called PSMA PET/CT (prostate specific membrane antigen positron emission tomography/computed tomography), is superior to current scanning techniques. PSMA PET/CT has capacity for wide availability at relatively low cost. Performing a single better test rather than several less accurate scans will also be cheaper, improve patient experience and expose patients to lower amounts of radiation.

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This is a randomised study at multiple centres around Australia comparing PSMA-PET/CT to conventional imaging. If the initial work-up does not demonstrate tumour spread, patients will cross-over to the other imaging arm. We hope to prove that PSMA-PET/CT has superior diagnostic performance, should be used as a firstline test for staging prior to surgery or radiotherapy and will result in significant changes to patient management. Results of this trial will be used to support funding of this new technology in Australia and internationally. The trial has now closed to recruitment and enrolled 300 participants in Australia.

8. e-TC 2.0 – Testicular Cancer A team of cancer survivors, researchers and clinicians developed the e-TC website, which provides evidencebased information and psychological strategies for coping with the challenges associated with testicular cancer. This study aims to evaluate the use and satisfaction with the e-TC website in men who have finished treatment for testicular cancer and are feeling stressed, down or worried about their cancer coming back. Men were recruited through clinicians at participating centres and online via search engine and social media advertising. The study has now closed to recruitment with 40 participants having taken part.

9. FASTRACK II – Kidney Cancer Surgery is the standard treatment for primary kidney cancer. However, in some cases, surgery is either not possible or other health problems make surgery high risk. This study involves a relatively new, highly precise multidirectional radiotherapy technique called Stereotactic Ablative Body Radiotherapy (SABR) which will be applied to all participants. The aim of the study is to test the ability of the technique to control cancer within the kidney for those people for whom surgery is not an option, and to examine the side effects of the treatment, including how it may affect your kidney’s function. This study is led by TROG and Co-badged by ANZUP Cancer Trials Group and is now closed to recruitment and is in follow up.

The importance of your support In line with the ACNC requirements, any changes made to these events, ANZUP documented and communicated clearly with our key stakeholders including the reasons why the decision had been made and to ensure the funds donated, were used in line with donors’ original intent and ANZUP’s charitable purpose. As a charity that is continuing to fundraise during this difficult time and being mindful of restrictions remaining on large gatherings, lack of confidence from participants to attend physical events and budget limitations, ANZUP has launched a new exciting digital campaign – Below the Belt #YourWay. So far, 2020 has been a year to remember. We have seen bushfires ravage NSW and Victoria, followed by a global pandemic that has thrown the world into a state of uncertainty and fear. In Australia it is estimated that charities will lose at least 20% of expected revenue due to COVID -19 with approximately 200,000 job losses across the sector in 2020. The Federal Government has acknowledged the difficult time and has provided cash flow support and Job Keeper payments for eligible charities as well as providing incentives for philanthropic funders to increase their distribution to charities. The community is encouraged to show their support where possible on-line and charities are urged to adapt to the crisis and update their digital communications to help supporters stay connected. ANZUP has been fortunate to keep working and our research and clinical trials have continued. We have made adjustments to suit the current climate, including new meeting formats and fundraising initiatives. The effect of the COVID -19 pandemic on ANZUP began almost immediately when the Below the Belt Pedalthon in Melbourne had to be postponed. This followed the announcement that the Grand Prix was cancelled on the same weekend, due to restrictions on large public gatherings. From this day on, ANZUP planned for the next twelve months with a new approach for fundraising and public events. ANZUP also made the difficult decision to postpone the Below the Belt Pedalthon, Sydney in September due to current restrictions and also for the safety of the riders and supporters. We plan to reschedule the Below the Belt Pedalthon events in 2021.

The new challenge invites you in September to run, walk or cycle as many km’s as you can. You can do it at your home or in your office, or outdoors, whatever you choose. We are doing this to raise awareness and much needed funds for below the belt cancer research. Keeping your mind and body healthy. Do it as a team, with your family, with work colleagues, or with a friend or by yourself. Do it every day or some days in September. It’s #YourWay. It will be open to all in Australia and New Zealand. We encourage you to visit www.belowthebelt.org.au/yourway to find out more and to join the challenge #YourWay. We are also committed to donor care and ensuring we communicate with our key donors, developing new communication and branding support collateral as well as planning for future appeals, while working through our database.

You can help raise funds and awareness for below the belt cancers today. Whether it is through a workplace-giving program, an event, a challenge, telling your story, have someone speak at your event or make a regular giving donation, we hope you can join our many supporters and help us pursue our mission of improving the lives of people with these cancers through an ANZUP clinical trial. For more information on how you can help please contact Julijana Trifunovic - Head of Partnerships and Engagement at Julijana.trifunovic@anzup.org.au

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Make a difference with ANZUP We need your help to improve outcomes for people affected by these below the belt (prostate, testicular, penile, bladder and kidney) cancers and for future generations. Any donation, large or small, goes straight into the hands of experts to find the answers we need.

To find out more or to donate please go to https://anzup.org.au/donate/donateStep1Details.aspx

How can you get involved? Support comes in all shapes and sizes. Whatever you are interested in doing to support ANZUP, let us know and we will help support you on the journey. Participate in a fitness challenge – Get involved with a fun run, triathlon, walkathon the options are endless! – and represent ANZUP.

Sponsor a fundraiser – Donate to a friend or family member participating in a sports festival.

Donate In Memoriam – Honour your loved one with a contribution in their name or asking for donations in lieu of funeral flowers.

Hold an event – Be it a morning tea, a raffle, a barbie, trivia night, or book club, we can support you to run your own fundraising event.

Provide in-kind support – In-kind donations include providing the budget for a specific staff member, meeting room use, auctionable goods for fundraising, advertising and creative support, and can help us deliver more interesting and educational information.

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Give in Lieu of a Gift – Donate towards a special occasion in lieu of a traditional gift. For example, a wedding, birthday or retirement celebration. If it is your special occasion, why not ask for donations instead.

Noel Castan Fellowship ANZUP was delighted to launch the Noel Castan Fellowship at the 2019 Annual Scientific Meeting (ASM) in Brisbane. The Noel Castan Fellowship was established by Anita Castan, in memory of her husband, who passed away from cancer two decades ago. “I understand the value of supporting clinical trials and take this opportunity to congratulate ANZUP on its many successes to date and its collaborative approach.” The aim of the Noel Castan Fellowship is to build ANZUP’s research capacity and increase the translation of information collected from our trials, which will contribute to better understanding of how to optimise patient care. The Noel Castan Fellowship was awarded to ANZUP members, Hui-Ming Lin and Kathyrn Schubach.

Bioinformatics project, Hui-Ming Lin The Noel Castan Fellowship enables Hui-Ming to carry out research on blood specimens and clinical data from the ENZAMET trial. The ENZAMET trial, which was led by ANZUP, is an international Phase 3 trial on 1,125 men with metastatic hormone-sensitive prostate cancer (mHSPC). The trial found that addition of enzalutamide to standard testosterone suppression improved survival and delayed PSA/ clinical progression. However, not all men responded to enzalutamide, and responders eventually stop responding. The aim of the project is to look for biological markers in blood that can predict who will respond to enzalutamide, as this will help decide the best course of treatment. Additionally, these biological markers will help uncover mechanisms of enzalutamide resistance, which will lead to new treatments that can improve the outcome of men with mHSPC. The type of biological markers that Hui-Ming will be investigating are lipids and cytokines, which are respectively linked to fat metabolism and the immune response. Perturbations in these aspects have been reported in prostate cancer, but are not well understood. The project will hopefully increase the understanding of the role of fat metabolism and the immune response in prostate cancer, in addition to identifying biological markers that will improve the outcomes of men with mHSPC.

Quality of Life Project, Kath Schubach Kath’s work will help provide a unique opportunity to maximise ANZUP’s contribution to the field by developing ‘Quality of Life’ (QOL) questions to use in trials, and use existing data innovatively to drive the field forward. Her work has the potential to improve the integration of QOL data into future ANZUP clinical trials. It will provide a resource for clinicians not familiar with the QOL instruments when designing a trial and enhance collaboration within the multidisciplinary team of ANZUP. We have a clinically meaningful research opportunity to draw attention to “the patient experience” and to align with the mission of ANZUP’s clinical research. Kath will enrol for a PhD by publication at the University of Canberra. There is also the opportunity through this Fellowship to explore and contribute to knowledge of symptom clusters within and across tumour streams as an emerging science to understanding patient experience. Kath is working closely with clinicians and researchers in supportive care to develop new interventions and questions to address the symptoms identified in a rationale and evidence based way. Active dissemination is being directed to five main audiences: a) U ro-oncology clinical staff b) P atients olicy makers c) P hird sector cancer organisations d) T e) A cademic audiences. Kath is also looking at publishing the research in open access peer reviewed journals, (e.g. Journal of clinical oncology, European Urology and BJUi International Journal of Nursing Studies). As well as presenting at conferences such as ANZUP’s Annual Scientific Meeting (ASM) and other relevant national and international meetings. The design of workshops and train the trainer programs to increase capacity and skill of the clinical workforce in this area will also be areas of priority. Kath will also be working closely with ANZUP’s Consumer Advisory Panel (CAP) to ensure dissemination at a community level to men and their families, enabling them to make informed decisions about treatments and participation in clinical trials.

Fundraising heroes Thank you to the Burns family who once again ran a very successful New Year’s Day fundraiser donating the funds to support cancer research. Well done to Torey Burns who has taken over the baton for this event from her sister Kyah. They have raised nearly $4000 since starting this community event in 2014. Thank you for supporting Bec’s Troops and ANZUP to support the Below the Belt Research Fund. A LITTLE BELOW THE BELT 61

Get inspired and host your own A great idea is just the beginning… here are a few key dates and events to get you started when planning your own fundraising event:

July

October

Y UR WAY

5th – 11th Mental Health Week – between dealing with cancer and COVID-19 we need to look after our mental health. Host a morning tea and check in with those around you.

August November

Winter – host a bonfire or cosy movie night for a gold coin donation.

Organise a fundraising BBQ.

September

December

Prostate Cancer Awareness Month 1st – 30th – Below the Belt #YourWay challenge. Cycle #YourWay, step #YourWay, run #YourWay every day or some days.

Help support the Below the Belt #YourWay Christmas Appeal.

How does your donation make a difference? All contributions, large or small, get us closer to finding better treatments for cancer. Clinical trials are a costly exercise, but the outcomes are so worthwhile. This is where your donated funds go:

$500 – $1000

$5000 – $10000

Sponsor a travel fellowship

Support a concept workshop

Will support the attendance of an ANZUP multidisciplinary member at a conference or scientific meeting.

Will allow us to hold a face-to-face Concept Development Workshop to discuss new research ideas and concepts to consider developing into a future grant applications.

$50k – $250k

Kick off a pilot study Will allow us to invest in a pilot study to test the feasibility of promising drug therapies, surgical methods, post-operative care and palliative care options.

Any donation to ANZUP over $2 is fully tax deductible. If you would like to donate to ANZUP, you can donate through our website www.anzup.org.au/donate or by calling ANZUP on +61 2 9562 5042. 62 A LITTLE BELOW THE BELT

Below the Belt Pedalthon Below the Belt Pedalthon, since 2014:

BELOW THE BELT PEDALTHON EVENTS

24 2000

BELOW THE BELT RESEARCH FUND PROJECTS AWARDED FUNDING

RIDERS

$1.75 MILLION RAISED

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Below the Belt Pedalthon

The Below the Belt Pedalthon The Below the Belt Pedalthon was founded in 2014 to promote awareness of the highly prevalent but less ‘glamorous’ below the belt cancers. The idea for the Pedalthon came from Simon Clarke, a testicular cancer survivor, who wanted to make a difference in his own way and give back by raising awareness and funds for below the belt cancer research.

DR CAMILLE SHORT RECEIVES HER BELOW THE BELT RESEARCH FUND AWARD FROM ASSOCIATE PROFESSOR GUY TONER

SIMON CLARKE AND HIS MEDICAL ONCOLOGIST ASSOCIATE PROFESSOR PETER GRIMISON AT THE BELOW THE BELT PEDALTHON

ANZUP’s major fundraising event is held in Sydney and Melbourne each year, and every cent raised through the Below the Belt Pedalthon goes directly towards clinical trial research via the Below the Belt Research Fund. This funding initiative supports ANZUP members to develop novel research projects. To date, this funding has been awarded to 24 ANZUP members to help gather the evidence needed to develop full scale clinical research studies.

We invite you in September to cycle #YourWay, walk #YourWay or run #YourWay as many km’s as you can.

ANZUP’s goal is to raise enough funds to be able to fully support its own trials, and the Pedalthon strongly supports a step in that direction. Unfortunately due to the COVID–19 pandemic restrictions and for the health of our community we are postponing the Below the Belt Pedalthon events until 2021. However we can’t postpone our research as it is critical for the health of our community. We cannot postpone the engagement of those involved in our Pedalthon. We cannot postpone for those who want to support this important cause.

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PEDALTHON START LINE

Below the Belt #YourWay

This September cycle, run or walk to raise awareness and funds for below the belt cancer research We are delighted to announce our new campaign – Below the Belt #YourWay and invite you in September to cycle #YourWay, walk #YourWay or run #YourWay as many km’s as you can.

What’s #YourWay?

Register for the inaugural Below the Belt #YourWay challenge today. To find out more or register go to http://www. belowthebelt.org.au/yourway or email the Below the Belt #YourWay team at belowthebelt@anzup.org.au.

You can do it at home, at the office, or in the great outdoors. Whatever you choose we are doing this to raise awareness and much needed funds for below the belt cancer research. Keeping both your mind and body healthy.

Our Sydney Below the Belt Pedalthon will be back again in 2021 – in the meantime, we invite you to do it #YourWay.

Do it as a team, with your family, with work colleagues, with a friend or alone. Do it every day or some days in September. It’s #YourWay. Open to all in Australia and New Zealand.

Do it #YourWay and help raise $100,000 for below the belt cancer research. Improve your fitness, raise awareness and help fund future clinical trials for below the belt cancers.

Challenge: C ycle, walk or run as many kilometres as you can When:

Between 1 - 30 September 2020

Why:

o raise funds and awareness T for below the belt cancers

Cost:

Registration costs will be basic (includes cap) $35 or premium (includes cycling or running / walking tee and cap) $65 person.

How:

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Below the Belt #YourWay

#YourWay inspiration Meet Professor Dickon Hayne, the master behind the Your Way song

PROFESSOR DICKON HAYNE WITH DAUGHTERS NATASHA AND ZOE.

The Below the Belt #YourWay campaign idea originated from the song, Your Way donated to ANZUP by Professor Dickon Hayne. Professor Hayne is a clinical academic who leads the urological research team within the School of Surgery and is responsible for undergraduate education in urology at the University of Western Australia. Professor Hayne is a member of ANZUP and chair of the ANZUP Bladder Urothelial and Penile (BUP) subcommittee. He is also a very talented musician and so are his two daughters Natasha and Zoe. How did the Your Way song originate? Lots of time indoors with the kids during COVID-19 lockdown. Always enjoyed writing songs but struggle with singing – enter Natasha (18) and Zoe (12) to the rescue! The song deals with resolution of difficulties and I suppose is mostly about empowering choice but also the acceptance of uncertainty. What does the song mean to you and your daughters? A moment in time. It will always remind us of the lockdown and singing and playing together. Why did you want to donate the song to ANZUP? I’ve been involved with ‘musical projects’ with ANZUP before and I suppose it came from there. I’m always looking for ways to try get music into my day job. Not only are you musical, you are also a Professor of Urology and chair of the ANZUP BUP Cancer Subcommittee. How did you get into music? With some parental ‘encouragement’ I took up the violin at the age of 6 and soon realised violin practice could be used as an excuse to get out of the washing up. I attended the Guildhall School of Music, London as a youngster but soon (fortunately) realised my place in the gene pool of classical musicians and decided to do medicine.

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I really enjoyed playing in bands with my friends through school, medical school and as a junior doctor but with surgical practice and a young family it’s hard to find as much time for music as I might like. Your two daughters sing the Your Way song. How did they enjoy being part of the recording and the theme for the #YourWay campaign? Both Natasha and Zoe have enjoyed singing and had voice lessons at their school John Curtin College of the Arts. They were a little reluctant about the recording idea to begin with. As the recording date got nearer and with more practice under their belts they got less nervous and more excited. On the day, the recording team at Currambine Community Centre (run by City of Joondalup) were amazing and really put the girls at ease. They loved the experience and seemed to take it all in their stride. It was really fun. You will need to ask them how they feel about being part of #YourWay campaign but I think they’re cool with it. Will you be riding, walking or running in the #YourWay challenge? Riding, but not very fast One of the key messages of the #YourWay campaign is clinical trials #yourway #yourchoice. As a clinician what message do you want to give the general public about clinical trials? Clinical trials are a key component of improving cancer outcomes. The opportunity to participate in a clinical trial is something we should strive to offer in so many more clinical situations. I really hope that those affected by urologic cancers will choose to take part in ANZUP trials for their own benefit and for the benefit of others. A special thanks to the City of Joondalup youth recording program and team for their support in recording the Your Way song. spotify:album:0KppAsYukI620ibqxTKjxw

Thanks to Corporate Supporters and In-Kind Supporters Corporate Supporters

In-Kind Supporters

We are very fortunate to have our corporate supporters and partners who enable ANZUP to better support our members and, ultimately, patients and their families. Our 2019/2020 corporate supporters include:

We acknowledge and thank the following organisations for the generosity they have shown by providing their services pro-bono.

Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Ipsen, Janssen and Pfizer Oncology.

Active Display Group, AFI Branding, The Saturday Paper and FC Lawyers.

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Y UR WAY

www.belowthebelt.org.au/yourway ANZUP Cancer Trials Group Level 6, Lifehouse Building, 119-143 Missenden Road, Camperdown NSW 2050 Tel: +61 2 9562 5042 Email: anzup@anzup.org.au www.anzup.org.au