Clinical Trials in Progress: CIRCULATE-US

Background

Currently, determination of whether adjuvant chemotherapy is required for colon cancer is based on tumor/node/metastasis staging and clinical and pathological factors. However, the absolute benefit of adjuvant therapy for stage II and III colon cancer is ~5% and ~25% to 30%, respectively, indicating that the benefit is limited to a subgroup of patients with colon cancer. Therefore, more precise approaches to defining patients at risk for recurrence are required.

The detection of circulating tumor DNA (ctDNA) in blood samples has evolved significantly over the past decade, and studies have investigated the clinical and prognostic value of ctDNA in early-stage colon cancer. Recent studies identified ctDNA status as one of the most powerful prognostic factors and a surrogate for minimal residual disease (MRD) for patients with early-stage colon cancer. However, at this time, the clinical use of ctDNA for the determination of adjuvant therapy is not well established and represents an unmet need for research. CIRCULATE-US, a prospective phase 2/3 trial, will be investigating MRD-based adjuvant therapy for patients with early-stage colon cancer with intensified and deintensified adjuvant therapy approaches by using ctDNA status as a surrogate for MRD status. This trial will use Signatera ctDNA testing to determine the ctDNA status of patients entering the study.

Inclusion Criteria

Patients with confirmed stage IIIA or stage IIIB mismatch repair–proficient colon adenocarcinoma (T1-3, N1/N1c) will be included in this study. Patients with T4 or N2 disease will be excluded from cohort A to exclude the potential negative impact of a possible false-negative result of ctDNA testing on the survival of patients. Patients who have positive ctDNA results from commercially obtained Signatera testing and stage II and IIIC colon adenocarcinoma and who otherwise meet the rest of the eligibility criteria can be enrolled in cohort B. Eligible patients will have adequate organ function and a baseline radiologic exam within 28 days before enrollment without evidence of metastatic disease. Patients with mismatch repair–deficient colon cancer, tumor-related bowel perforation, or distal tumor extension of 12 cm or less will be excluded from this study.

Patient Accrual Information

• Open date: The study was activated on March 10, 2022, and is currently actively recruiting across the United States.
• Accrual goal: The study is powered to enroll 1912 patients with resected stage III A, B, and patients with positive ctDNA and stage II or IIIC colon adenocarcinoma.
• Percent accrued: In progress.

Study sites: The study is activated across the National Cancer Institute’s National Clinical Trials Network.

Contact Information

Primary Investigator:
Arvind Dasari, MD, MS
Gastrointestinal Oncology
The University of Texas MD Anderson Cancer Center
Houston, TX
ADasari@mdanderson.org

Co-Primary Investigator:
Christopher Lieu, MD
Medical Oncology
University of Colorado Cancer Center
Aurora, CO
christopher.lieu@cuanschutz.edu
Phone: +81 4 7133 1111
Fax: +81 4 7134 6928