Sue S. Yom, MD, Ph.D., Professor and Vice Chair, Strategic Advisory
Department of Radiation Oncology; Professor, Otolaryngology-Head and Neck Surgery at University of California San Francisco. In this video, she speaks about the Association of plasma tumor tissue modified viral HPV DNA (TTMV) with tumor burden, treatment type, and outcome: A translational analysis from NRG-HN002.
There are currently no biomarkers that have been validated prospectively in randomized studies for resected colon cancer (CC) to determine the requirement for adjuvant chemotherapy (AC). However, circulating tumor DNA (ctDNA) represents a highly specific and sensitive approach (especially when combined with serial monitoring) for identifying minimal/molecular residual disease (MRD) post-surgery in CC patients (pts), and may outperform traditional clinical and pathological features in predicting risk of recurrence. Patients with CC who do not have detectable ctDNA (ctDNA-) have a considerably lower chance of recurrence and may avoid the toxicity associated with AC. Furthermore, the best AC regimen for CC patients with detectable ctDNA (ctDNA+) who are at a very high risk of recurrence has not been determined. We hypothesize that in patients whose CC has been removed, ctDNA status could be used to risk stratify for AC decisions.
Up to 1,912 patients with resected stage III A, B (all patients) and stage II, IIIC (ctDNA+ exclusively) CC will be enrolled in this prospective phase II/III experiment. Those who are ctDNA- (Cohort A) will be randomized to immediate AC with fluoropyrimidine (FP) + oxaliplatin (Ox) for 3-6 months per known guidelines vs. serial ctDNA monitoring based on post-operative ctDNA status using tailored and tumor informed assay (SignateraTM, bespoke assay). Patients who test positive for ctDNA after surgery or after serial monitoring (Cohort B) will be randomized to FP+Ox vs. more intensive AC with irinotecan (I) for 6 months. Time to ctDNA+ status (phase II) and disease-free survival (DFS) in phase III in the immediate vs. delayed AC arms are the key objectives for Cohort A. For both the phase II and phase III phases of the trial, the main endpoint for Cohort B is DFS in the FP+Ox vs FP+Ox+I arms. Secondary endpoints include the proportion of detectable ctDNA post-operatively, time-to-event outcomes (overall survival and time to recurrence) by ctDNA status, and assessment of adjuvant medication compliance. For exploratory correlative research, biospecimens such as archival tumor tissue, post-operative, and serial matched/normal blood samples will be obtained. Active enrolment in the NCTN began in early 2022. U10-CA-180868, -180822; UG1CA-189867; NCT05174169 clinical trial information.