Platform study of circulating tumor DNA directed adjuvant chemotherapy in colon cancer (CLAUDIA colon cancer, KCSG CO22-12)

Abstract

Background Tumor-informed circulating tumor DNA (ctDNA) analysis allows for the sensitive detection of minimal residual disease (MRD) and has the potential to enhance patient stratification for adjuvant chemotherapy. We hypothesize that intensifying adjuvant chemotherapy in colon cancer patients with postoperative MRD positivity may reduce recurrence and improve survival outcomes. Methods This multi-center platform trial (NCT05534087) consists of a prospective observational study (Part 1) and an interventional randomized trial (Part 2). In Part 1, approximately 1,200 patients with colon cancer will be screened for MRD at 3-6 weeks postoperatively using a tumor-informed, hybrid-capture-based ctDNA MRD assay that tracks up to 100 patient-specific somatic variants identified through tumor whole-exome sequencing. Key eligibility criteria includes: age >= 19 years, <= 6 weeks post-curative resection, pathological diagnosis of colon adenocarcinoma, stage III or stage II with high-risk features requiring adjuvant chemotherapy with FOLFOX/CAPOX, and no macroscopic residual disease. All patients in Part 1 will complete 3 months of standard adjuvant FOLFOX/CAPOX while awaiting MRD results. Patients with MRD positivity will be screened for the Part 2 clinical trial following the completion of the initial 3 months of treatment titled "Randomized Controlled Phase III Trial of Treatment Intensification in Stage II-III Colon Cancer Patients with Positive MRD after Curative Resection." MRD-negative patients are managed at the investigator&apos;s discretion. Part 2 investigates the superiority of an experimental arm (modified FOLFIRINOX for 3 months) compared to a control arm (FOLFOX/CAPOX for 3 months). The primary endpoint of the Part 2 randomized trial is the 3-year disease-free survival (DFS), while secondary endpoints include the 5-year overall survival, 5-year DFS, treatment-related adverse events, treatment compliance, and patient-reported outcomes. A total of 236 patients will be enrolled and randomized in a 1:1 ratio, assuming a hazard ratio of 0.64, 80% power, a two-sided alpha of 0.05, and a 10% dropout rate. Discussion This trial will evaluate the effect of adjuvant chemotherapy intensification in colon cancer patients who are MRD-positive after curative surgery. This will enable a personalized adjuvant chemotherapy strategy based on postoperative MRD assessment in colon cancer.