CRC.10

1-Primary Objective
ctDNA-ve Cohort (Arms 1 + 2):
Phase II: To compare time to ctDNA (+ve) status in ctDNA (-ve) cohort following resection of stage III colon cancer treated with immediate vs delayed (based on serial ctDNA surveillance) chemotherapy. Time to positive event is defined as time from randomization to the first ctDNA positive result for the immediate arm (Arm 1) and to the 2nd ctDNA positive result for the delayed arm (Arm 2) to allow for the potential effect of delayed adjuvant chemotherapy. Patients recurred without a positive ctDNA result will be considered to have ctDNA positive status at the time of recurrence for both study arms.
Phase III: To compare time to DFS event (recurrence, second primary colorectal cancer or death) in ctDNA (-ve) cohort following resection of stage III colon cancer treated with immediate vs delayed (based on serial ctDNA surveillance) chemotherapy.
ctDNA+ve Cohort (Arms 3 + 4):
Phase II and III: To compare time to DFS event (recurrence, second primary colorectal cancer or death) in ctDNA (+ve) cohort following resection of colon cancer treated with 5-FU (or capecitabine) and oxaliplatin x 6 months or 5-FU, oxaliplatin and irinotecan x 6 months.
2-Secondary Objectives
1 To describe the prevalence of detectable ctDNA in patients with stage III colon cancer following surgical resection. The finding will be reported together with the main results of the Phase II portion of the trial.
2 To estimate time-to-event outcomes (overall survival and time to recurrence) by ctDNA marker status and treatment
3 To assess the compliance of adjuvant chemotherapy.
4 Exploratory Objectives
5 To explore the kinetics of quantitative ctDNA levels over time and its association with time to event outcomes (RFS, OS, and TTR).
6 To characterize genomic profiles associated with recurrence using a ctDNA assay in patients with resected colon cancer.
We are doing this study because we want to find out if this approach is better or worse than the usual approach for your colon cancer. The usual approach is defined as care most people get for colon cancer that has been treated with surgery. This study contains two cohorts, the ctDNA negative cohort (-ve, Cohort A) and the ctDNA positive cohort (+ve, Cohort B) based on the post-operation ctDNA test results. A randomized phase II/III study will be conducted within each cohort.
Cohort A (ctDNA -ve): patients will be randomized into immediate treatment arm (Arm 1) and delayed (based on serial ctDNA surveillance) treatment arm (Arm 2). The primary endpoint for phase II of Cohort A is time to ctDNA (+ve) status (TTPos) and the primary endpoint for phase III of Cohort A is disease-free survival (DFS). Patients on Arm 2 who turned ctDNA (+ve) will cross over to Cohort B study.
Cohort B (ctDNA +ve): patients will be randomized to receive either FP (5-FU/ capecitabine + oxaliplatin, Arm 3) or FOLFIRINOX (5-FU + oxaliplatin + irinotecan, Arm 4) for 6 months. The primary endpoint for both phase II and III of Cohort B is DFS.
Synchronized accrual hiatus: there will be an accrual hiatus about 12-14 months between phase II and phase III portion of the trial in both Cohorts to allow obtaining the phase II results. The hiatus of the two cohorts will largely overlap. If the phase II result of Cohort B turns out to be negative, we will stop the crossover of Cohort A Arm 2 patients to Cohort B.