PO.CT01.05 · 临床试验

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

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

编号 CT157 展板 21 时间 4/20 02:00–05:00 区域 Section 52 主讲 Remond Fijneman, PhD

分会场 Phase II and Phase III Clinical Trials

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作者与单位

Ingrid A. Franken¹, Suzanna J. Schraa¹, Steven L. C. Ketelaars², Carmen Rubio-Alarcón², Teunise Bisschop-Snetselaar¹, Bregje Adriaans¹, Miranda van Dongen², Linda J. W. Bosch², Mirthe Lanfermeijer², Samuel Angiuoli³, Amy E. Greer³, Ellen Verner³, Jennifer B. Jackson⁴, Rebecca A. Previs⁴, Veerle M. H. Coupe⁵, Daan van den Broek², Gerrit A. Meijer², Jill Phallen⁶, Victor E. Velculescu⁶, Anna J. S. van Tetering-Houben¹, Jeanine M. L. Roodhart¹, Niels F. M. Kok², Frederieke H. van der Baan¹, Mark Sausen³, Miriam Koopman¹, Geraldine R. Vink¹, Remond J. A. Fijneman², the PLCRC-MEDOCC group

¹University Medical Center Utrecht, Utrecht, Netherlands,²The Netherlands Cancer Institute, Amsterdam, Netherlands,³Labcorp, Baltimore, MD,⁴Labcorp, Durham, NC,⁵Amsterdam University Medical Centers, Amsterdam, Netherlands,⁶Johns Hopkins University School of Medicine, Baltimore, MD

摘要 Abstract

Introduction: Patients with stage II colon cancer (CC) not classified as high risk do not receive adjuvant chemotherapy (ACT) according to Dutch guidelines. However, 15-20% of patients with stage II CC experience disease recurrence, highlighting an 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 CC 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 CC and no indication for ACT, and randomized to the intervention arm undergo postoperative tumor-informed MRD testing using PGDx elio® plasma resolve or Labcorp Plasma Detect®. Labcorp Plasma Detect is a highly sensitive ctDNA assay integrating whole genome sequencing (WGS) analyses of formalin-fixed paraffin-embedded tumor tissue, germline, and plasma cell-free DNA. Patients who test ctDNA-positive are offered 4 cycles of adjuvant capecitabine + oxaliplatin. ctDNA-negative patients in the intervention arm and patients in the control arm receive standard of care followup. For all patients, 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 multicenter collection of tumor tissue and blood have been optimized across 29 Dutch hospitals. At present, 525 patients have been randomized. Of the 263 patients in the intervention arm, 212 provided consent for immediate postoperative ctDNA analysis (83%). Of the 197 currently available results, 16 (8,1%) had detectable ctDNA of which 11 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 46 days (IQR 40-53). 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 CC.

利益披露 Disclosure

I. A. Franken, Labcorp ). DoMore Diagnostics ). S. J. Schraa, None. S. L. C. Ketelaars, Labcorp ). C. Rubio-Alarcón, Labcorp ). T. Bisschop-Snetselaar, None.. B. Adriaans, None.. M. van Dongen, None.. L. J. W. Bosch, None.. M. Lanfermeijer, None. S. Angiuoli, Labcorp Employment. A. E. Greer, Labcorp Employment. E. Verner, Labcorp Employment. J. B. Jackson, Labcorp Employment. R. A. Previs, Labcorp Employment. V. M. H. Coupe, Labcorp ). D. van den Broek, Delfi Diagnostics ). G. A. Meijer, Labcorp ). Delfi Diagnostics ). CRC Bioscreen Other Business Ownership. Exact Sciences ). Sysmex ). Sentinel Ch SpA ). J. Phallen, None. V. E. Velculescu, Delfi Diagnostics Stock, Other Business Ownership, Patent. Labcorp Stock, Other Business Ownership. Qiagen Patent. Sysmex Patent. Agios Patent. Genzyme Patent. Esoterix Patent. Ventana Patent. Mana T Bio Patent. Viron Therapeutics Other, advisor. Epitope Other, Advisor. A. J. S. van Tetering-Houben, GSK ). Incyte ). Merck ). Natera ). Nordic ). Labcorp ). Pierre Fabre ). Servier ). J. M. L. Roodhart, GSK ). Servier ). BMS ). ABBVIE ). Pierre Fabre ). Incyte ). Xilis ). Cleara ). Hub Organoids BV ). DoMore Diagnostics ). N. F. M. Kok, Delfi Diagnostics ). Natera ). Labcorp ). F. H. van der Baan, Labcorp ). M. Sausen, Labcorp ). BMS Employment. M. Koopman, Amgen ). Bayer ). BMS ), Other, Advisor. Merck-Serono ). Nordic Pharma ), Other, Advisor. Roche ). Servier ), Other, Advisor. Sirtex ). Labcorp ). Pierre Fabre ). Sanofi-Aventis ). G. R. Vink, Natera ). BMS ). Merck ). Servier ). Labcorp ). Bayer ). Sirtex ). Nordic Pharma ). Pierre Fabre ). Lilly ). Delfi Diagnostics ). R. J. Fijneman, Labcorp ). Delfi Diagnostics ). Natera ). Solvias (Cergentis BV) ).

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