Background Accurate detection of patients with minimal residual disease (MRD) after resection of localized colon cancer remains an unmet clinical need as these patients might benefit from adjuvant chemotherapy (ACT). For stage II colon cancer, ACT is only indicated in patients with a pT4 tumor without a deficient mismatch repair system (dMMR), according to Dutch guidelines. However, recurrence rate (RR) in stage II colon cancer is still 15-20%. Circulating tumor DNA (ctDNA), consisting of small fragments of DNA containing tumor-specific mutations, has been shown to be a promising biomarker for MRD and a strong predictor for recurrent disease when detectable after resection. The MEDOCC-CrEATE trial investigates how many stage II colon cancer patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces RR in these patients.

Methods The MEDOCC-CrEATE study follows the ‘trials within cohorts' (TwiCs) design. Patients with colorectal cancer are included in the Prospective Dutch ColoRectal Cancer (PLCRC) cohort study and give informed consent for collection of clinical data and biomaterials, including tissue and blood samples. Additionally, patients are invited to give their consent for future randomization without being informed when allocated to the control group receiving standard of care. In MEDOCC-CrEATE 1320 stage II colon cancer patients without an indication for ACT will be included and randomized 1:1 into an experimental and a control arm. In the experimental arm, tissue and blood samples are analyzed after surgery for tissue-informed detection of plasma ctDNA, using the PGDx elio™ Platform. Patients with detectable ctDNA after surgery will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin. Patients in the experimental arm without detectable ctDNA and patients in the control arm receive standard follow-up. The primary endpoint is the proportion of patients accepting ACT when ctDNA is detectable after resection. Most important secondary endpoint is 2-year RR, but also includes 5-year RR, disease free and overall survival, time to recurrence, quality of life and cost-effectiveness of the ctDNA-based treatment strategy. Data will be analyzed by intention to treat. To our knowledge, MEDOCC-CrEATE is the first trial in which a ctDNA guided strategy for adjuvant chemotherapy in colon cancer is investigated. The first patient was enrolled in August 2020. MEDOCC-CrEATE is now open for inclusion in 8 hospitals in the Netherlands. So far, 9 patients have been randomized. The number of participating hospitals will be expanded to 20-25 hospitals to include all 1320 patients within 3 years. MEDOCC-CrEATE has been registered in the Netherlands Trial Register: NL6281/NTR6455.

Citation Format: Suzanna J. Schraa, Karlijn L. Van Rooijen, Dave E. Van Der Kruijssen, Carmen Rubio Alarcón, Jillian Phallen, John Simmons, Sam Angiuoli, Amy E. Greer, Veerle M. Coupé, Helma M. Van Grevenstein, Sjoerd Elias, Helena M. Verkooijen, Miranda M. Van Dongen, Linda J. Bosch, Daan Van Den Broek, Gerrit A. Meijer, Victor E. Velculescu, Remond J. Fijneman, Geraldine R. Vink, Miriam Koopman. MEDOCC-CrEATE trial in progress: effectiveness of adjuvant chemotherapy in stage II colon cancer patients with positive circulating tumor DNA [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT251.