Testing ctDNA as a Biomarker for Adjuvant Therapy Intensity in Stage 3 Colon Cancer (NRG-GI008, The “CIRCULATE-US” Study)

April 12 2022

NRG-GI008: Colon Adjuvant Chemotherapy Based on Evaluation of Residual Disease (CIRCULATE-US)

Currently, the standard of care for patients with stage III colon cancer is a combination of fluoropyrimidines and oxaliplatin, however, data from historical trials and the ACCENT database suggest that over 40% of this patient population is cured by surgery alone without the need for adjuvant therapy. Additionally, several trials have proved that the current standard of care has only made incremental advances in these outcomes. This data suggests not all stage III colon cancer patients require intensive adjuvant therapy.

NRG-GI008, or “the CIRCULATE-US study”, was designed to test if ctDNA status can be used as a potential biomarker in identifying colon cancer patients who are high-risk for recurrence and determine the intensity of their adjuvant chemotherapy accordingly. This trial would provide the first prospective data for the testing of ctDNA as a predictive integral biomarker for the response of adjuvant FOLFOX chemotherapy in patients with stage III colon cancer.

“NRG-GI008 will help determine how we might use circulating tumor DNA (ctDNA) to guide the best therapy for patients with stage III colon cancer. We know that patients who are ctDNA negative appear to have good outcomes, and patients that are ctDNA positive have high rates of cancer recurrence. NRG-GI008 will help us understand if patients who are ctDNA negative need chemotherapy, and whether intensification of treatment can help patients who are ctDNA positive. ctDNA is an incredibly exciting technology and trials like NRG-GI008 will help us utilize these tests to help our patients receive the best treatment possible for their cancer,” stated Arvind Dasari, MD, MS, of the University of Texas MD Anderson Cancer Center and Christopher Lieu, MD, of University of Colorado Anschutz Medical, the Co-Principal Investigators of the NRG-GI008 trial.

The CIRCULATE-US study will accrue patients with stage III resected colon cancer or circulating tumor DNA positive (ctDNA+) Stage II or Stage IIIC resected colon cancer. Patients will undergo central ctDNA testing and then will be assigned to either Cohort A with ctDNA negative (ctDNA-) status or to Cohort B with ctDNA+ status. Cohort A, ctDNA- patients will be stratified by colon cancer stage and intended chemotherapy treatment then will be randomly assigned to receive either mFOLFOX6/CAPOX or they will be monitored via serial ctDNA testing. Patients in Cohort B will be stratified by intended chemotherapy treatment and post-op ctDNA status then will be randomly assigned to receive either mFOLFOX/CAPOX or to receive mFOLFIRINOX.

The primary objective of this trial in Phase II is to compare the time to ctDNA-positive status in the ctDNA-negative cohort following resection of stage III colon cancer treated with immediate versus delayed chemotherapy. The primary objective of this trial in Phase III is to compare time to a disease-free survival (DFS) event in the ctDNA-negative cohort following resection of stage III colon cancer. Both Phase II and III will also compare the time to a DFS event in the ctDNA positive cohort following resection of colon cancer that was treated with adjuvant chemotherapy. Secondary objectives include describing the prevalence of detectable ctDNA in patients with stage III colon cancer following surgical resection, estimating time-to-event outcomes by ctDNA marker status and treatment ,and assessing the compliance of adjuvant chemotherapy.

Learn more about this trial at ClinicalTrials.gov

Protocol documents and materials are located on the CTSU website

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