1. Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): Study protocol for a trial within a cohort study
- Author
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Schraa, S. J., Van Rooijen, K. L., Van Der Kruijssen, D. E.W., Rubio Alarcón, C., Phallen, J., Sausen, M., Simmons, J., Coupé, V. M.H., Van Grevenstein, W. M.U., Elias, S., Verkooijen, H. M., Laclé, M. M., Bosch, L. J.W., Van Den Broek, D., Meijer, G. A., Velculescu, V. E., Fijneman, R. J.A., Vink, G. R., Koopman, M., Dunker, Mich S., Lutke Holzik, Martijn F., Hoekstra, Ronald, Sommeijer, Dirkje W., Van Der Bilt, Jarmila D.W., Consten, Esther C.J., Cirkel, Geert A., Burghgraef, Thijs A., Van Der Schans, Emma M., Nieboer, Peter, Rietbroek, Ron C., Dekker, Jan Willem T., Verschoor, Arjan J., Talsma, Koen A.K., Brosens, Rebecca P.M., Helgason, Helgi H., Marinelli, Andreas W.K.S., De Hingh, Ignace H.J.T., Oldenhuis, Corina N., Jansen, Jan, Van Halteren, Henk K., Stockmann, Hein B.A.C., Beeker, Aart, Bosscha, Koop, Pruijt, Hans F.M., Spierings, Leontine E.A.M.M., Valkenburg-Van Iersel, Liselot B.J., Vles, Wouter J., De Jongh, Felix E., Van Cruijsen, Hester, Heikens, Joost T., Zimmerman, David D.E., Van Alphen, Robert J., Schiphorst, Anandi H.W., Van Leeuwen-Snoeks, Lobke L., Vogelaar, Jeroen F.J., Peters, Natascha A.J.B., Epidemiology and Data Science, APH - Methodology, CCA - Cancer Treatment and quality of life, Pathology, Internal medicine, Orthopedic Surgery and Sports Medicine, VU University medical center, Surgery, Robotics and image-guided minimally-invasive surgery (ROBOTICS), RS: NUTRIM - R3 - Respiratory & Age-related Health, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, MUMC+: MA Medische Oncologie (9), Medical Biology, Nephrology, and Oncology
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0301 basic medicine ,Oncology ,Male ,Cancer Research ,Neoplasm, Residual ,Colorectal cancer ,Cost-Benefit Analysis ,COLORECTAL-CANCER ,Circulating Tumor DNA ,Study Protocol ,0302 clinical medicine ,RESIDUAL DISEASE ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,Prospective Studies ,Colectomy ,Netherlands ,Randomized Controlled Trials as Topic ,RISK ,education.field_of_study ,RANDOMIZED CONTROLLED-TRIAL ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Colon cancer ,Oxaliplatin ,Chemotherapy, Adjuvant ,CELL-FREE DNA ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Practice Guidelines as Topic ,SURVIVAL ,Female ,medicine.drug ,Cohort study ,Adult ,medicine.medical_specialty ,Population ,TwiCs ,lcsh:RC254-282 ,Disease-Free Survival ,LEUCOVORIN ,Capecitabine ,03 medical and health sciences ,Internal medicine ,Genetics ,medicine ,Biomarkers, Tumor ,Humans ,RECURRENCE ,education ,Neoplasm Staging ,Intention-to-treat analysis ,business.industry ,Liquid Biopsy ,ctDNA ,Patient Acceptance of Health Care ,medicine.disease ,Minimal residual disease ,FLUOROURACIL ,Adjuvant chemotherapy ,030104 developmental biology ,Quality of Life ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
Background Accurate detection of patients with minimal residual disease (MRD) after surgery for stage II colon cancer (CC) remains an urgent unmet clinical need to improve selection of patients who might benefit form adjuvant chemotherapy (ACT). Presence of circulating tumor DNA (ctDNA) is indicative for MRD and has high predictive value for recurrent disease. The MEDOCC-CrEATE trial investigates how many stage II CC patients with detectable ctDNA after surgery will accept ACT and whether ACT reduces the risk of recurrence in these patients. Methods/design MEDOCC-CrEATE follows the ‘trial within cohorts’ (TwiCs) design. Patients with colorectal cancer (CRC) are included in the Prospective Dutch ColoRectal Cancer cohort (PLCRC) and give informed consent for collection of clinical data, tissue and blood samples, and consent for future randomization. MEDOCC-CrEATE is a subcohort within PLCRC consisting of 1320 stage II CC patients without indication for ACT according to current guidelines, who are randomized 1:1 into an experimental and a control arm. In the experimental arm, post-surgery blood samples and tissue are analyzed for tissue-informed detection of plasma ctDNA, using the PGDx elio™ platform. Patients with detectable ctDNA will be offered ACT consisting of 8 cycles of capecitabine plus oxaliplatin while patients without detectable ctDNA and patients in the control group will standard follow-up according to guideline. The primary endpoint is the proportion of patients receiving ACT when ctDNA is detectable after resection. The main secondary outcome is 2-year recurrence rate (RR), but also includes 5-year RR, disease free survival, overall survival, time to recurrence, quality of life and cost-effectiveness. Data will be analyzed by intention to treat. Discussion The MEDOCC-CrEATE trial will provide insight into the willingness of stage II CC patients to be treated with ACT guided by ctDNA biomarker testing and whether ACT will prevent recurrences in a high-risk population. Use of the TwiCs design provides the opportunity to randomize patients before ctDNA measurement, avoiding ethical dilemmas of ctDNA status disclosure in the control group. Trial registration Netherlands Trial Register: NL6281/NTR6455. Registered 18 May 2017, https://www.trialregister.nl/trial/6281
- Published
- 2020