Circulating tumor DNA (ctDNA) testing can potentially help identify minimal/molecular residual disease (MRD) post-curative-intent surgery in patients with colorectal cancer (CRC). ctDNA can be used to identify MRD-negative patients that have already benefited from surgery/definitive therapy and may avoid unnecessary adjuvant chemotherapy. It also allows for consideration and/or intensification of systemic treatment for MRD-positive patients, who ideally need ‘adjuvant’ therapy to avoid relapse. Early detection of MRD using a personalized, tumor-informed ctDNA assay provides a unique opportunity to identify optimal treatment options for patients, which can, in turn, result in improved survival and quality of life in CRC survivors.
The study is a prospective, multicenter clinical trial that utilizes a personalized ctDNA assay (SignateraTM bespoke mPCR NGS), designed to track tumor-specific mutations in patients with stage II/III CRC for MRD determination and molecular monitoring. A total of 1,000 patients will be enrolled at >50 US sites and will be followed for up to 2 years with periodic blood collection, timed with the standard-of-care visits (post-operative/surgery visit, prior to initiation of systemic chemotherapy, with each cycle of chemotherapy and with each surveillance visit). Primary objective: To examine the impact of Signatera on adjuvant treatment decisions and to determine the rates of CRC recurrence while asymptomatic. To estimate the true percent of cases with a change in post-surgical treatment, under the assumptions of a ±5% margin of error and a 95% confidence level, a minimum of 921 patients will be enrolled. Secondary endpoints: Determine overall survival, rate of MRD clearance (MRD+ to MRD-), adjuvant treatment rates, surgery and/or locoregional treatment rates for oligometastatic recurrence, patient satisfaction, and physician utility. This will be the first real-world study of MRD testing and will provide one of the largest prospective datasets, with serial blood collection at landmark visits, in patients with stage II/III CRC.
Clinical trial identification
Editorial assistance was provided by Meenakshi Malhotra, PhD from Natera, Inc. San Carlos, US.
Legal entity responsible for the study
P.M. Kasi: Advisory/Consultancy: Natera, Inc.; Advisory/Consultancy: Foundation Medicine; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Taiho Pharmaceutical; Research grant/Funding (institution): Advanced Accelerator Applications; Research grant/Funding (institution): Array Biopharma; Research grant/Funding (institution): Bristol-Myers Squibb; Research grant/Funding (institution): Celgene. S. Sawyer, J. Guilford, M. Munro, S. Ellers, N. Hook, S. Krinshpun: Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc. S. Moshkevich: Leadership role, Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment, Officer/Board of Directors: Natera, Inc.. P.R. Billings: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc.; Officer/Board of Directors: OmniSeq; Officer/Board of Directors: Mission Bio. A. Aleshin: Leadership role, Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment: Natera, Inc.; Advisory/Consultancy: Mission Bio; Advisory/Consultancy: Notable Labs.