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Testicular Cancer Research Highlights
by Dr Ben Tran, Medical Oncologist, Peter MacCallum Cancer Centre and Walter and Eliza Hall Institute of Medical Research. ANZUP Germ Cell Subcommittee Chair.
Testicular cancer is now highly curable, but that wasn’t always the case. Up until the late 1970s, testicular cancer was a very aggressive disease with a very poor prognosis. However, the development BEN TRAN, ANZUP GERM of cisplatin based CELL SUBCOMMITTEE CHAIR chemotherapy, tested in clinical trials, changed the face of testicular cancer, from a devastating disease in young men, to a highly curable disease.
Although testicular cancer patients now have mainly excellent outcomes, we can still do better. This is why ANZUP is involved in clinical trials in testicular cancer through its clinical trials program.
ANZUP has subcommittees for each of its diseases, which includes the Germ Cell (Testicular Cancer) Subcommittee. The subcommittee has had a very productive year with trials ongoing as well as studies in the pipeline and the presentation of promising concepts that could lead to future trials.
Some highlights include the following:
TIGER Trial
This study aims to demonstrate how well standard-dose combination chemotherapy works compared to highdose combination chemotherapy in treating patients with germ cell tumours where the cancer persists after a first round of chemotherapy.
This trial is now open at 4 sites in Australia, with recruitment at 9 out of 60 patients. This study also aims to recruit 420 patients internationally.
iTestis Database
iTestis is a user-friendly, multi-disciplinary, web-based testicular cancer database. Data collected within iTestis will provide better understanding of treatment patterns in Australia and identify how treatments for Australian patients can be improved. iTestis also has the capacity to be linked to tumour tissue from individual patients and through this linkage, there will be scope to answer some of the biological research questions that might lead to new treatment approaches.
iTestis is continuing to expand, opening at multiple sites across the country,and gaining interest from cancer centres in other parts of the globe.
DR ROB HAMILTON, DR BEN TRAN AND DR FRITHA HANNING DISCUSSING ANZUP TRIALS - WHAT HAPPENS NEXT FOR OUR TRIALS, AT THE ANZUP ANNUAL SCIENTIFIC MEETING.
P3BEP Trial
The current gold standard practice for the treatment of germ cell tumours is the use of a chemotherapy combination called BEP which consists of three chemotherapy agents, Bleomycin, Etoposide and Cisplatin administered on a 3 weekly cycle. BEP is given with a drug called pegylated G-CSF (or pegfilgrastim) which stimulates white blood cell production.
The purpose of this study is to determine whether giving the same dose of BEP on a 2-weekly schedule will be more effective than a 3-weekly schedule and will be well tolerated. The 2-weekly schedule is called ‘accelerated BEP’.
This study has continued to recruit well despite the challenging circumstances presented by COVID-19 restrictions. Across ANZ, UK and US sites 144 patients have now been recruited.
In addition, blood and tissue from consenting P3 BEP trial participants will be collected for translational research studies.
Some other projects in the pipeline are as follows:
Micro RNA Analyses
There is an urgent need to develop markers that can better guide chemotherapy decision making and also identify patients at very low risk of recurrence where the intensity of CT scans during active surveillance could be reduced. One biomarker, miR-371, appears promising with high sensitivity and specificity for the detection of lingering testicular germ cell tumours, and subsequently, has the potential to satisfy both needs.
The CLIMATE study aims to determine the clinical use of miR-371 in clinical stage 1 testis cancer. The CLIMATE study has been designed through the ANZUP concept development workshops, and will have sufficient funding to start in 2021. The aim will be to recruit approximately 200 patients with stage 1 testicular cancer over 2-3 years from 7-8 hospital sites.
PRESTIGE
Research in testicular germ cell tumours (TGCT) now focuses on helping TGCT survivors live long, healthy, and productive lives. The aim of some new clinical trials is finding ways to minimise treatment related complications, whilst maintaining the excellent outcomes.
Within the global TGCT academic community, there is interest in exploring primary Retroperitoneal Lymph Node Dissection* (RPLND) as an alternative to chemotherapy for curing selected men with advanced TGCT, namely those with disease just located in their retroperitoneum, with involved lymph nodes measuring 3cm or less.
While the short- and long-term effects of chemotherapy on health related quality of life (HRQoL) are well described in this group of cancer patients, there are minimal data regarding the impact of RPLND alone on HRQoL. Such data are necessary to inform a randomised study between chemotherapy and primary RPLND in this setting. Alternatively, if primary RPLND becomes increasingly used, data regarding HRQoL are necessary to properly inform the recommendation for surgery over chemotherapy in these young patients.
The PRESTIGE study aims to add to the literature, by describing the impact of primary RPLND on HRQoL, with particular attention to sexual function. PRESTIGE will also describe the peri-operative complications (i.e. the time between surgery and going home) and other surgical measures. Additionally, through collection of serum, PRESTIGE aims to explore whether the biomarker miR-371 has potential to assist in selecting patients most likely to be cured by primary RPLND alone and avoid chemotherapy.
The PRESTIGE study examining the changes in HRQoL in patients undergoing primary RPLND aims to open in 2021 as well. However, given the extremely specialised nature of RPLND surgery, only a few sites around Australia will be participating.
To find out more about ANZUP’s testicular cancer trials go to page 44 or ask your GP or specialist if there is a clinical trial suitable for you.
*remove lymph nodes at the back of the abdomen that may contain cancer cells.
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: Open & recruiting
Location: Australia wide & Internationally
Activated sites: 4 (Australia)
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. Up to 420 patients will be enrolled in Australia, New Zealand and other countries. Currently we have 9 patients enrolled and 4 sites open in Australia.
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
P3BEP
Status: Active & recruiting
Location: Australia wide & Internationally
Activated sites: 61
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 61 sites open in Australia and New Zealand, and 144 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 •Calvary Mater Newcastle •Chris O’Brien Lifehouse • Concord Repatriation General
Hospital •Macquarie Cancer Clinical Trial •Nepean Hospital • Northern NSW Local Health District -The Tweed Hospital •Princes of Wales •Royal North Shore Hospital •Sydney Adventist Hospital
QLD •Princess Alexandra •Queensland Childrens Hospital •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 • Beatson West of Scotland Cancer
Centre •Bristol University Hospital •Velindre Hospital • Cambridge University Hospital
Paediatric •University Hospital Southampton •Royal Marsden Hospital •St James Hospital - Leeds •St Bartholomews Hospital •Nottingham University Hospital •Belfast City Hospital •Derriford Hospital, Plymouth
USA • Washington University School of
Medicine •Rady Children’s Hospital •Augusta University Medical Centre •Vanderbilt University Medical Centre • Lucile Packard Children’s Hospital
Stanford • Memorial Health University Medical
Centre • University of Mississippi Medical
Centre •Geisinger Medical Center •Palmetto Health Richland • Methodist Children’s Hospital of
South Texas •University of Wisconsin Hospital •East Tennessee Children’s Hospital • Miller Children’s and Women’s
Hospital Long Beach •Roswell Park Cancer Center • USC / Norris Comprehensive
Cancer Care •Broward HealthCare •Dana Farber Cancer Center • UT Southwestern Simmons Cancer
Center • LA Biomedical Research Institute at
Harbor- UCLA •Dayton Children’s Hospital • University of Texas Science Center at San Antonio •Mayo Clinic • Advocate Children’s Hospital – Oak
Lawn •Carolinas Medical Center • USC/ Norris Comprehensive Cancer
Care
