TRACC: Tracking mutations in cell-free DNA to predict relapse in early colorectal cancer—A randomized study of circulating tumour DNA (ctDNA) guided adjuvant chemotherapy versus standard of care chemotherapy after curative surgery in patients with high risk stage II or stage III colorectal cancer (CRC)

TPS4120 Background: Adjuvant chemotherapy (ACT) is routinely offered to patients with high risk (HR) stage II or stage III CRC following potentially curative surgery. Over 50% of stage III and > 80% of stage II patients are cured by surgery alone but are being exposed to unnecessary chemotherapy with short- and long-term side effects. Post-operative ctDNA identifies minimal residual disease (MRD) after surgery in CRC. Our national study, TRACC, compares ctDNA guided versus standard of care (SoC) decision making in patients undergoing ACT. Methods: This is a UK-wide, multi-centre, prospective, two-arm, randomised trial. Patients with HR risk stage II or stage III CRC who have undergone R0 resection and have detectable ctDNA in their pre-surgical sample are eligible. Patients who undergo neoadjuvant chemoradiotherapy (CRT) for locally advanced rectal cancer with detectable ctDNA pre-CRT are also eligible. Patients are randomised in a 1:1 ratio to receive either SoC ACT or ctDNA guided ACT. In the ctDNA guided arm, patients who are ctDNA negative post-operatively have chemotherapy de-escalated i.e., 3 months(m) of Capecitabine and Oxaliplatin (CAPOX) doublet ACT is reduced to 3 m single agent Capecitabine; 6 m single agent Capecitabine reduced to no chemotherapy. In this group, ctDNA is re-tested at 3 months and if detectable, patients receive 3 months of CAPOX. Primary end-point is 3-year disease free survival (DFS). Secondary end-points include overall survival, neurotoxicity, quality of life and health economics. Based on a standard 3-year DFS of 75% in SoC ACT arm, to demonstrate a non-inferiority margin of 1.25, 810 patients are required per arm (85% power, α = 0.1). Stratification is by tumour staging and site of primary tumour. Target accrual is over 4 years. The study opened to recruitment in January 2020 and is supported by the MRC-NIHR Efficacy and Mechanism Evaluation Grant ( NIHR128529 ). Clinical trial information: NCT04050345 .