Dr. Kozuch on the Evaluation of ctDNA in the CIRCULATE-US Trial in Resected CRC

Peter Kozuch, MD, medical oncologist, site director, Division of Hematology and Medical Oncology, Mount Sinai West, co-chair, Mount Sinai Health System, Disease Focus Group Gastrointestinal Oncology Multidisciplinary Program, associate director, Mount Sinai Health System, Hematology and Medical Oncology Fellowship Program, discusses the the phase 2/3 CIRCULATE-US trial (NCT05174169) evaluating chemotherapy decisions for patients with resected colorectal cancer (CRC) based on circulating tumor DNA (ctDNA) status.

CIRCULATE-US is enrolling patients with resected stage II CRC who are ctDNA positive to help determine the optimal chemotherapy regimen in this setting. After undergoing an analysis of ctDNA determined by the Signatera personalized minimal residual disease (MRD) assay, enrolled patients who are ctDNA positive will be randomly assigned to adjuvant chemotherapy with modified fluorouracil, oxaliplatin, and irinotecan (mFOLFIRINOX) in the experimental arm, or 5-fluorouracil/leucovorin/oxaliplatin (mFOLFOX6) or capecitabine plus oxaliplatin (CAPOX) in the control arm.

Additionally, the trial is also enrolling patients with resected stage III CRC who are ctDNA negative. These patients will be randomly assigned to undergo ctDNA observation with no treatment, or receive chemotherapy with mFOLFOX6 or CAPOX with ctDNA observation for up to 96 weeks. If patients with stage III CRC become ctDNA positive, they will be randomly assigned to receive mFOLFIRINOX, or mFOLFOX6 or CAPOX.

Looking to the future, there will be many spaces in which quantitative ctDNA will be helpful in the field of CRC, Kozuch says. Most immediately, determining ctDNA’s role in making decisions about post-operative chemotherapy will be crucial. Kozuch emphasizes the importance of enrolling eligible patients into the CIRCULATE-US trial.

Identifying MRD status through ctDNA could help identify patients at higher risk of recurrence and metastatic disease, allowing them to receive chemotherapy to potentially help to eradicate the disease, and it could allow clinicians to identify patients who do not need chemotherapy if they are ctDNA negative following resection, Kozuch concludes.