This research study is comparing two standard of care treatment options based on blood test results for participants who have metastatic colorectal cancer. The names of the potential treatments involved in this study are: - Active surveillance - FOLFIRI treatment - Nivolumab treatment - Encorafenib/Binimetinib/Cetuximab treatment
Name: FOLFIRI Protocol
Name: ACTIVE SURVEILLANCE
Name: Nivolumab Protocol
Name: Encorafenib/Binimetinib/Cetuximab Protocol
Description: Disease-free survival (DFS) between ctDNA-positive patients treated with additional treatment of FOLFIRI and ctDNA-positive patients who are untreated
Measure: Disease-free survival (DFS) Time: 5 yearsDescription: Compare the clearance rate of ctDNA in ctDNA-positive patients between patients treated with additional treatment of FOLFIRI and those who are untreated
Measure: Clearance rate of ctDNA Time: 7 MonthsDescription: Overall survival (OS) between ctDNA-positive patients treated with additional adjuvant therapy (Arm 1) and ctDNA-positive patients who are untreated (Arm 2)
Measure: Overall Survival (OS) Rate Time: 5 yearsDescription: Determine clearance rate of ctDNA-positive patients treated with nivolumab in an exploratory MSI/mismatch repair deficient cohort
Measure: Clearance rate of ctDNA of Arm 4: Nivolumab Treatment Time: 13 monthsDescription: Determine the disease-free survival (DFS) of ctDNA-positive patients treated with nivolumab in an exploratory MSI/mismatch repair deficient cohort
Measure: Disease-free survival (DFS) of Arm 4: Nivolumab Treatment Time: 5 yearsDescription: Determine the clearance rate of ctDNA-positive patients treated with encorafenib, binimetinib, and cetuximab in an exploratory BRAF V600E cohort.
Measure: Clearance rate of ctDNA of Arm 5: Encorafenib/Binimetinib/Cetuximab Treatment Time: 7 monthsDescription: Determine the disease-free survival DFS of ctDNA-positive patients treated with encorafenib, binimetinib, and cetuximab, in an exploratory BRAF V600E cohort.
Measure: Disease-free survival (DFS) of Arm 5: Encorafenib/Binimetinib/Cetuximab Treatment Time: 5 yearsDescription: Examine the correlation of ctDNA clearance as a surrogate marker for disease burden
Measure: ctDNA clearance as Marker Time: 13 MonthsDescription: Compare lead time to recurrence and sensitivity of predicting recurrence between ctDNA and tumor markers
Measure: Lead time to recurrence Time: 5 yearsAllocation: Randomized
Parallel Assignment
There is one SNP
Determine the clearance rate of ctDNA-positive patients treated with encorafenib, binimetinib, and cetuximab in an exploratory BRAF V600E cohort.. Disease-free survival (DFS) of Arm 5: Encorafenib/Binimetinib/Cetuximab Treatment. --- V600E ---
Determine the disease-free survival DFS of ctDNA-positive patients treated with encorafenib, binimetinib, and cetuximab, in an exploratory BRAF V600E cohort.. ctDNA clearance as Marker. --- V600E ---
- Patients who are MSI-high or have a BRAF V600E mutation are excluded from Arm 1 (FOLFIRI) and Arm 2 (Active Surveillance). --- V600E ---
- Participants must have normal organ, marrow, and hematologic function as defined below: - Hemoglobin ≥9 g/dL (5.58 mmol/L) - Total bilirubin ≤ 1.5 (25.65 μmol/L) - Platelets ≥100,000/μL Encorafenib, binimetinib, and cetuximab Specific Exclusion Criteria for BRAF V600E mutant Cohort: - Patients with a BRAFV600E mutation and who are MSI-H are excluded from Arm 5 (ENCO/BINI/CETUX) - Prior therapy with a BRAF inhibitor (e.g., encorafenib, dabrafenib, vemurafenib) and/or a MEK inhibitor (e.g., binimetinib, trametinib, cobimetinib). --- V600E ---
- Encorafenib in combination with binimetinib and cetuximab is one of the first effective regimens to target the BRAF V600E-mutation in colorectal cancer. --- V600E ---