2232 - Phase II Trial of Locally Ablative Therapy for Oligoprogressive Gastrointestinal Malignancies: The LIVELONG Trial
Presenter(s)
J. Sun1, M. E. Daly2, X. Zhao1, M. Parikh3, T. Le4, T. Dodd4, L. Morris4, L. Qi5, S. Feinstein6, C. Park7, A. Shah8, and E. Kim3; 1Department of Radiation Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, CA, 2Department of Radiation Oncology, University of California - Irvine, Orange, CA, 3Department of Hematology and Oncology, University of California Davis Comprehensive Cancer Center, Sacramento, CA, 4University of California Davis Comprehensive Cancer Center, Sacramento, CA, 5Public Health Science, University of California Davis, Davis, CA, 6Department of Radiation Oncology, University of California, Irvine, Orange, CA, 7Department of Hematology and Oncology, University of California Irvine School of Medicine, Irvine, CA, 8Department of Radiology, University of California Davis Comprehensive Cancer Center, Sacramento, CA
Purpose/Objective(s):
Background: Oligoprogression, defined as progression at a limited number of metastatic sites (=5) during otherwise effective systemic therapy, is increasingly recognized as a distinct clinical state in metastatic solid tumors. In this setting, locally ablative therapy (LAT), including stereotactic ablative radiotherapy (SABR) or interventional radiology (IR)-guided ablation, may eradicate resistant clones while preserving systemic disease control. The only randomized prospective evidence supporting LAT in oligoprogressive disease is derived from non-small cell lung cancer, where NCCN guidelines now recommend ablative therapy for limited progression on an otherwise effective systemic regimen. By contrast, prospective data for the use of LAT for oligoprogression in gastrointestinal (GI) malignancies remain limited. Furthermore, the low incidence of many GI malignancies makes standalone prospective trials challenging to complete. The LIVELONG phase II trial (NCT06101277) is a pragmatic basket study designed to rapidly evaluate the impact of LAT on time to next systemic therapy across a range of oligoprogressive GI cancers.Materials/Methods:
LIVELONG is a single-institution, prospective, open-label Phase II pragmatic trial enrolling adults (=18 years) with histologically or biochemically confirmed metastatic GI malignancies, including Cohort 1 - small bowel, colorectal, appendiceal and Cohort 2 - pancreatic, ampullary, and biliary cancers (including gallbladder and intrahepatic and extrahepatic cholangiocarcinoma). Eligible patients must have received at least one line of systemic therapy for metastatic disease with =3 months of clinical benefit at the discretion of the treating provider and subsequently develop =5 new or progressing metastatic lesions, all amenable to LAT. Patients must be candidates to continue their current systemic therapy with a planned treatment interruption of =30 days to permit ablative treatment. Participants receive SABR or IR-guided ablation to all progressing lesions at the discretion of the treating physician and continue the same systemic therapy. The primary endpoint is disease control at 3 months, defined as continuation in systemic therapy without changes or permanent discontinuation for 3 months following first day of ablative local therapy. Secondary endpoints include grade =3 non-hematologic LAT-related adverse events, time to treatment failure, and median overall survival stratified by primary tumor type. Each cohort enrolls up to 50 patients (a total 100 patients for two cohorts) using a three-stage design (lead-in n=15; expansion 1 n=10; expansion 2 n=25; Cohorts 1 including a, b and c group, Cohorts 2 including x, y and z group). Simon’s minimax two-stage design (n=25) tests a null disease control rate of 10% versus 30% (one-sided a=0.05, 80% power). With full accrual (n=50), power increases to 98%. Patients are followed for up to 5 years. Enrollment began in September 2023.Results: NA
Conclusion: NA