Abstract CT221: MEDOCC-CrEATE trial update: Feasibility of measuring circulating tumor DNA post-surgery to guide adjuvant chemotherapy in stage II colon cancer patients

Abstract Introduction: Patients with stage II colon cancer not classified as high risk (pT4 microsatellite stable) do not receive adjuvant chemotherapy (ACT) according to Dutch guidelines. However, 15-20% of these patients experience a disease recurrence, indicating the unmet clinical need to identify patients who could benefit from ACT. Observational studies demonstrate that postoperative circulating tumor DNA (ctDNA) is indicative of minimal residual disease (MRD) and a strong prognostic biomarker for disease recurrence. Aim: The MEDOCC-CrEATE trial aims to assess 1) the proportion of stage II colon cancer patients with detectable postoperative ctDNA accepting ACT, and 2) whether ctDNA-guided ACT reduces 2-year recurrence rate (RR). Methods: MEDOCC-CrEATE is an interventional trial following the ‘trial within cohorts’ design. Participants of the Prospective Dutch Colorectal Cancer cohort with stage II colon cancer and no indication for ACT randomized to the intervention arm undergo postoperative tumor-informed ctDNA testing through integrated whole genome sequencing (WGS) analyses of formalin-fixed paraffin-embedded tumor tissue DNA (80x), germline DNA (40x), and plasma cell-free DNA (30x). This test was newly introduced in Q2 2024. Post-surgery ctDNA-positive patients are offered 4 cycles of capecitabine plus oxaliplatin. Patients in the intervention arm who test ctDNA-negative and patients in the control arm receive standard of care follow-up. Blood is collected every 6 months for 3 years to monitor disease recurrence. The primary endpoint is the proportion of patients with detectable postoperative ctDNA willing to receive ACT. Secondary endpoints include 2-year RR, disease-free and overall survival, quality of life and cost-effectiveness of ctDNA-guided ACT. The study will continue until 10 patients with detectable postoperative ctDNA are treated with ACT in the intervention arm. Results: Logistics for timely collection of tumor tissue and blood have been optimized across 29 Dutch hospitals. At present, 400 patients have been randomized. Of the 200 patients in the intervention arm, 159 provided consent for immediate postoperative ctDNA analysis (80%). Of the 148 currently available results, 7 (4,7%) had detectable ctDNA of which 5 started ACT. The median time from surgery to blood collection was 15 days (IQR 12-19), with a median turnaround time from surgery to ctDNA result of 47 days (IQR 39-53). Conclusion: Multicenter postoperative tumor-informed ctDNA testing for MRD is operationally and technically feasible within the clinically relevant 8-12 week window to start ACT. The observed ctDNA detection rate is in accordance with expectations and the study design. Upon study finalization, the results will be used for health technology assessment to demonstrate the putative clinical utility of ctDNA-guided ACT in stage II colon cancer. Citation Format: Ingrid Franken, Suzanna Schraa, Karlijn van Rooijen, Dave van der Kruijssen, Carmen Rubio-Alarcon, Steven Ketelaars, Sietske van Nassau, Teunise Bisschop-Snetselaar, Bregje Adriaans, Jill Phallen, Samuel Angiuoli, Amy Greer, Ellen Verner, Veerle Coupe, Helena Verkooijen, Miranda van Dongen, Linda Bosch, Mirthe Lanfermeijer, Daan van den Broek, Gerrit Meijer, Victor Velculescu, Mark Sausen, Miriam Koopman, Remond J. A. Fijneman, Geraldine Vink. MEDOCC-CrEATE trial update: Feasibility of measuring circulating tumor DNA post-surgery to guide adjuvant chemotherapy in stage II colon cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT221.