Abstract 521TiP
Background
For stage II colon cancer (CC) adjuvant chemotherapy (ACT) is only indicated in patients with a pT4 tumor without dMMR, according to current Dutch guidelines. However, accurate detection of patients with minimal residual disease (MRD) after resection remains an unmet clinical need considering the 15-20% recurrence rate (RR). Circulating tumor DNA (ctDNA), consisting of small fragments of DNA containing tumor-specific mutations, has been shown to be a strong predictor for recurrent disease when detectable after resection and presumably reflects a state of MRD. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces RR in these patients.
Trial design
This study follows the ‘trials within cohorts’ (TwiCs) design. Patients with colorectal cancer are included in the Prospective Dutch ColoRectal Cancer (PLCRC) cohort and give informed consent for collection of clinical data and biomaterials, including tissue and blood samples. Additionally, patients are being asked to give broad consent for future randomization without being informed when allocated to the control group receiving standard of care. MEDOCC-CrEATE is a subcohort within PLCRC in which 1320 stage II CC patients without an indication for ACT will be included and randomized 1:1 into an experimental arm 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 group without detectable ctDNA and patients in the control group 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 analysis.
Clinical trial identification
NL6281.
Editorial acknowledgement
Legal entity responsible for the study
Prof. dr. M. Koopman.
Funding
This study collaboration project is co-funded by PPP Allowance (grant LSHM19027) made available by Health∼Holland. MEDOCC-CrEATE is part of the COIN project, which is funded by the ZonMw ‘Personalised Medicine‘ program (project number 848101011), Personal Genome Diagnostics (PGDx) and CZ Healthcare Insurance. Co-funding was also gathered from the Dutch Digestive Foundation.
Disclosure
S. Schraa: Research grant/Funding (institution): Personal Genome Diagnostics. D.V.D. Kruijssen: Research grant/Funding (institution): Dutch Cancer Society; Research grant/Funding (institution): Roche. C. Rubio Alarcón: Research grant/Funding (institution): Personal Genome Diagnostics. M. Sausen: Full/Part-time employment: Personal Genome Diagnostics. J. Simmons: Shareholder/Stockholder/Stock options, Full/Part-time employment: Personal Genome Diagnostics. V. Velculescu: Advisory/Consultancy, Shareholder/Stockholder/Stock options, Officer/Board of Directors: Personal Genome Diagnostics; Advisory/Consultancy, Shareholder/Stockholder/Stock options, Officer/Board of Directors: Delfi Diagnostics. R. Fijneman: Research grant/Funding (institution): Personal Genome Diagnostics. G. Vink: Research grant/Funding (institution), Travel/Accommodation/Expenses: Servier; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Personal Genome Diagnostics. M. Koopman: Honoraria (institution), Research grant/Funding (institution): BMS; Honoraria (institution), Research grant/Funding (institution): Nordic Pharma; Honoraria (institution), Research grant/Funding (institution): Servier; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Merck-Serono; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Sirtex; Research grant/Funding (institution): Sanofi-Aventis; Travel/Accommodation/Expenses: Dutch Oncology Society (NVMO). All other authors have declared no conflicts of interest.