Phase II/III study of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer: NRG-GI005 (COBRA).

Authors

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Van K. Morris II

NRG Oncology, and University of Texas-MD Anderson Cancer Center, Houston, TX

Van K. Morris II, Greg Yothers , Scott Kopetz , Samuel A. Jacobs , Peter C. Lucas , Atif Iqbal , Patrick M Boland , Dustin A. Deming , Aaron James Scott , Howard John Lim , Theodore S. Hong , Norman Wolmark , Thomas J. George

Organizations

NRG Oncology, and University of Texas-MD Anderson Cancer Center, Houston, TX, NRG Oncology, and The University of Pittsburgh, Pittsburgh, PA, NRG Oncology, and University of Pittsburgh Cancer Institute, Pittsburgh, PA, NRG Oncology, and University of Pittsburgh School of Medicine, UPMC Hillman Cancer Center, Pittsburgh, PA, NRG Oncology, and Baylor College of Medicine, Houston, TX, Rutgers Cancer Institute of New Jersey, and the Alliance, New Brunswick, NJ, University of Wisconsin Carbone Cancer Center, and ECOG-ACRIN, Madison, WI, University of Arizona Cancer Center, and SWOG, Tucson, AZ, British Columbia Cancer Vancouver, and CCTG Co-Chair, Vancouver, BC, Canada, NRG Oncology and Massachusetts General Hospital, Harvard Medical School, Boston, MA, NRG Oncology, and The University of Florida Health Cancer Center, Gainesville, FL

Research Funding

U.S. National Institutes of Health

Background: There are currently no validated predictive biomarkers for stage II resected colon cancer (CC) after adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) shed into the bloodstream represents a highly specific and sensitive approach for identifying microscopic or residual tumor cells. For patients (pts) with CC, the detection of ctDNA is associated with persistent disease after resection and may outperform traditional clinical and pathological features in prognosticating risk for recurrence. We hypothesize that for pts whose stage II colon cancer has been resected and who have no traditional high-risk features, a positive ctDNA status may identify those who will benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III clinical trial, pts (N = 1,408) with resected stage II CC without traditional high-risk features and whom the evaluating oncologist deems suitable for active surveillance (i.e., not needing adjuvant chemotherapy) will be randomized 1:1 into 2 arms: standard-of-care/observation (Arm A), or prospective testing for ctDNA (Arm B). Postoperative blood will be analyzed for ctDNA with the Guardant Reveal assay, covering CC-relevant mutations and CC-specific methylation profiling. Pts in Arm B with ctDNA detected will be treated with 6 months of adjuvant (FOLFOX) chemotherapy. For all pts in Arm A, ctDNA status will be analyzed retrospectively at the time of endpoint analysis. The primary endpoints are clearance of ctDNA with adjuvant chemotherapy (phase II) and recurrence-free survival (RFS) for “ctDNA-detected” pts treated with or without adjuvant chemotherapy (phase III). Secondary endpoints will include time-to-event outcomes (OS, RFS, TTR) by ctDNA marker status and treatment, prevalence of detectable ctDNA in stage II CC, and rates of compliance with assigned intervention. Archived normal and matched tumor and blood samples will be collected for exploratory correlative research. Enrollment continues across North America to the 540-patient phase II endpoint. Support: U10-CA-180868, -180822; UG1CA-189867; GuardantHealth. Clinical trial information: NCT04068103.

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Abstract Details

Meeting

2022 ASCO Gastrointestinal Cancers Symposium

Session Type

Trials in Progress Poster Session

Session Title

Trials in Progress Poster Session C: Cancers of the Colon, Rectum, and Anus

Track

Colorectal Cancer,Anal Cancer

Sub Track

Tumor Biology, Biomarkers, and Pathology

Clinical Trial Registration Number

NCT04068103

DOI

10.1200/JCO.2022.40.4_suppl.TPS233

Abstract #

TPS233

Poster Bd #

P2

Abstract Disclosures

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First Author: Van K. Morris II

First Author: Van K. Morris II