CIRCULATE-US / NRG-GI008 — Colon Adjuvant Chemotherapy Based on Evaluation of Residual Disease (CIRCULATE-US): A Phase II/III Study of Circulating Tumor DNA (ctDNA)-Guided Adjuvant Therapy in Resected Stage II/III Colon Cancer

Phase 2/3 · Colorectal Cancer

Population

Patients with resected stage II/III colon cancer, stratified by post-operative circulating tumor DNA (ctDNA) status.

Primary Endpoint

Time to ctDNA positivity (de-escalation cohort) and disease-free survival (DFS)

Rationale

Post-surgical ctDNA is a powerful prognostic marker of molecular residual disease, but its role in directing adjuvant therapy is unproven. Many ctDNA-negative patients may be cured by surgery alone and could safely avoid chemotherapy toxicity, while ctDNA-positive patients relapse despite standard therapy and may need intensification.

What It Could Change

A positive result would establish ctDNA as a treatment-selection biomarker in colon cancer — sparing ctDNA-negative patients unnecessary adjuvant chemotherapy and justifying escalated therapy for ctDNA-positive patients, shifting adjuvant decisions from stage/pathology alone to molecular residual disease.