The PARSC Trial, a Prospective Study for the Assessment of Recurrence Risk in Stage II Colon Cancer Patients Using ColoPrint 1 2 3 4 5 6 7 8 8 9 R. Salazar , R. Rosenberg , M. Lutke Holzik , J. Marshall , J. J. M. Van Der Hoeven , B. Glimelius , F. Bibeau , L. Stork-Sloots , R.A. Bender , and J. Capdevila
1Institut Catala d’Oncologia, Barcelona, Spain, 2Klinikum rechts der Isar,Technische University Munich, Munich, Germany; 3Medisch Spectrum Twente, Enschede, Netherlands; 4Georgetown University Hospital, Washington DC; 5Medisch Centrum Alkmaar, Alkmaar, Netherlands; 6 8 7 9 Akademiska University Hospital Uppsala, Uppsala, Sweden; CRLC Val d’Aurelle, Montpellier, France; Agendia, Amsterdam, Netherlands and Irvine, CA; Vall d’Hebron University Hospital, Barcelona, Spain
Introduction
Schematic overview of prospective study
• Clinical trials have not yet shown convincingly if adjuvant chemotherapy is justified for stage II colon cancer patients, of whom 25% are at risk of recurrence. • An 18-gene expression profile, ColoPrint, has been developed for identifying colon cancer patients more likely to develop recurrent disease and who would be candidates for adjuvant chemotherapy. • The gene signature has been validated in independent cohorts of colon cancer patients (540 patients in validation studies and 322 in- silico)1,2.
Patient Information & Informed Consent
• Retrospective clinical studies showed that ColoPrint is able to predict recurrence of colon cancer in stage II patients independent of clinical factors.
2Rosenberg et al ASCO GI Symposium 2011 (abstract 358)
ColoPrint analysis
Year 1 Year 3 Year 5
Objectives
Training
HR = 3.6 (p=0.01); 5-year DMFS* Low risk (63% of patients) 91% (95% CI, 84-98%) High risk (37% of patients) 72% (95% CI, 58-88%)
Selection of final
Low risk
18-gene set & algorithm High risk
Standardization and validation
Validation of 18-gene profile
of analytical methods
Clinical validation study II (stage II-III); Munich hospital (n=233) (2) HR 1.8 (p=0.057) all stages; HR 4.13 (p=0.009) stage II
CRF 2 - 4
• Treatment is at the discretion of the physician, adhering to NCCN approved regimens or a recognized alternative. • ColoPrint result will not immediately be communicated to physician/patient (after enrollment has been completed).
• • • • •
Age ≥ 18 years. Adenocarcinoma of the colon. Stage II disease. Fresh tumor sample available. Written informed consent.
Exclusion criteria • • •
Prior malignancy (with the exception of basal cell carcinoma or cervical dysplasia). Any neo-adjuvant therapy. Synchronous tumors.
Patient information stage II (preliminary analysis of eligible and analyzable completed data)
Stage II
Validation study I, stage II (n=115)
Whole genome array
In-silico validation study (stage I-III); public datasets (n=322) HR = 2.8 (p<0.001) all stages
If eligible: CRF1
PARSC sample status to-date
Overview of ColoPrint development
Clinical validation study I (stage I-III); ICO Barcelona (n=208) (1) HR = 3.1 (P=0.001) all stages; HR = 3.27 (p=0.015) stage II
Quality check sample
Inclusion criteria
• Enrollment of 600 stage II patients.
± 4 weeks after surgery
RNARetain Sample Agendia
1Salazar et al. J Clin Oncol 2011; 29(1):17-24.
Training set (stage I-IV) Dutch hospitals (n=188) (1) HR = 3.41 (P< 0.0001)
Surgery
Treatment at discretion of investigator
Study design
1. To validate the power of risk assessment, and to compare the performance of ColoPrint vs the clinical risk assessment in estimating 3-year relapse rate in stage II colon cancer patients. 2. To assess the feasibility of using the ColoPrint test in clinical setting. 3. To prospectively compare risk assessment using the ColoPrint profile versus clinical parameters (based on phycisian assessment of risk and ASCO high-risk recommendations: T4, or perforation/obstruction, or G3, and/or inadequate node sampling (< 12 nodes) or poorly differentiated histology). 4. To establish the proportion of low risk and high risk ColoPrint profile in colon cancer patients. 5. To compare the performance of ColoPrint vs the clinical risk assessment in estimating 5-year relapse rate.
Ineligible (n=135) Not analyzable (n=87)
n=236
Variable
N
Age (years)
median
Stage I (n=119) Gender
Pending (n=76)
LN assessed
37 - 91
left
40
17
right
103
44
sigmoid
93
39
M
123
52
F
113
48
median
21
range
Eligible and analyzable Stage II (n=266)
LN >12
Eligible and analyzable Stage III (n=257)
Grade
pT
Localization of 26 study sites
71
range Localization
%
0 - 74
No
26
11
Yes
210
89
I
61
26
II
113
48
III
62
26
3
199
84
4
37
16
166
70
70
30
Physician Risk Assessment Low High
•
Current status
*DMFS; Disease Metastasis-Free Survival
• 26 centers open for patient recruitment.
Multivariate analysis stage II HR
95% CI
p-value
ColoPrint
3.53
1.33 - 9.36
0.011
ASCO recommendation*
1.9
0.75 - 4.83
0.174
* T4, high grade, perforation and/or less than 12 LN assessed
For more information and a list of all participating study sites, please check:
http://www.clinicaltrials.gov/ct2/show/NCT00903565
• Over 900 samples submitted worldwide. • Samples from 266 eligible and analyzable stage II patients included.