Alliance A022101: A pragmatic, randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: Evaluating Radiation, Ablation, and Surgery (ERASur).

person Kathryn Hitchcock University of Florida, Gainesville, FL info_outline Kathryn Hitchcock, Paul Bernard Romesser, Qian Shi, Jesse G. Dixon, Sepideh Gholami, Sarah B. White, Christina Wu, Christopher C. Goulet, Kyung-Wook Jee, Chadwick L. Wright, Rona Yaeger, Ardaman Shergill, Theodore S. Hong, Thomas J. George, Eileen Mary O'Reilly, Jeffrey A. Meyerhardt, Eric David Miller

Authors person Kathryn Hitchcock University of Florida, Gainesville, FL info_outline Kathryn Hitchcock, Paul Bernard Romesser, Qian Shi, Jesse G. Dixon, Sepideh Gholami, Sarah B. White, Christina Wu, Christopher C. Goulet, Kyung-Wook Jee, Chadwick L. Wright, Rona Yaeger, Ardaman Shergill, Theodore S. Hong, Thomas J. George, Eileen Mary O'Reilly, Jeffrey A. Meyerhardt, Eric David Miller Organizations University of Florida, Gainesville, FL, Memorial Sloan Kettering Cancer Center, New York, NY, Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN, Alliance Statistics and Data Management Center, Mayo Clinic, Rochester, MN, Northwell Health, New Hyde Park, NY, Medical College of Wisconsin, Milwaukee, WI, Mayo Clinic Arizona, Scottsdale, AZ, Billings Clinic, Billings, MT, Massachusetts General Hospital, Boston, MA, Ohio State University Comprehensive Cancer Center, Columbus, OH, Alliance Protocol Operations Office, University of Chicago, Chicago, IL, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, University of Florida Health Cancer Center, Gainesville, FL, Dana-Farber Cancer Institute, Boston, MA Abstract Disclosures Research Funding U.S. National Institutes of Health U.S. National Institutes of Health Background: For patients with oligometastatic colorectal cancer (CRC), aggressive local therapy of isolated metastases, particularly in the liver, has been associated with long-term progression-free survival and overall survival (OS) primarily based on retrospective evidence. However, in patients with limited metastatic CRC that is deemed inoperable or those with additional disease outside of the liver or lungs, the role of local ablative therapies, including microwave ablation (MWA) and stereotactic body radiation therapy (SBRT), to render patients disease free is less clear. Further, despite the long history of treating oligometastatic CRC with local therapy, which is provider biased and not evidence based, questions remain regarding the benefit of extending the paradigm of metastatic directed therapy to patients with more extensive disease. This trial seeks to use a pragmatic multimodality approach that mirrors the current clinical dilemma. This study is designed to evaluate the safety and efficacy of adding total ablative therapy (TAT) of all sites of disease to standard of care systemic treatment in those with limited metastatic CRC. Methods: A022101 is a National Clinical Trials Network randomized phase III study planned to enroll 364 patients with newly diagnosed metastatic CRC (BRAF wild-type, microsatellite stable) with ≤4 sites of metastatic disease on baseline imaging. Liver-only metastatic disease is not permitted, and lesions must be amenable to any combination of surgical resection, MWA, and/or SBRT with SBRT required for at least one lesion. Patients receive first-line systemic therapy for 4-6 months and are then randomized 1:1, stratified by number of metastatic organ sites (1-2 vs. 3-4), timing of metastatic disease diagnosis (de novo vs. secondary), and presence of metastatic disease outside the liver and lungs in at least one site. Patients in Arm 1 will receive TAT which consists of treatment of all metastatic sites with SBRT ± MWA ± surgical resection followed by standard of care systemic therapy. Patients in Arm 2 will continue with standard of care systemic therapy alone. The primary endpoint is OS. Secondary endpoints include event-free survival, treatment-related toxicities, and local recurrence with exploratory biomarker analyses. The study needs 346 evaluable patients combined in the 2 arms to demonstrate an improvement in OS with a hazard ratio of 0.7 to provide 80% power with a one-sided alpha of 5%. The trial utilizes a group sequential design with two interim analyses (25% and 50% of events) for futility. The trial activated in January 2023 and recruitment is ongoing. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org. U10CA180820 (ECOG-ACRIN); U10CA180868 (NRG); U10CA180888 (SWOG); Clinicaltrials.gov identifier: NCT05673148 Clinical trial information: NCT05673148.

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