Abstract A005: A multi-institutional randomized phase III trial of chemotherapy alone versus chemotherapy and ablative 5-fraction MRI-guided adaptive radiation therapy for locally advanced pancreatic cancer (LAP-ABLATE)

Abstract Background: Prospective studies demonstrate that chemotherapy and non-ablative radiation therapy (RT) achieve superior locoregional control (LRC) although have not improved overall survival (OS) relative to chemotherapy alone for patients with locally advanced pancreatic cancer (LAPC). Emerging data suggest that significant radiation dose escalation may further enhance LRC, and it has been hypothesized that in a subset of patients this may improve OS. However, delivering ablative radiation dose in 5 or fewer fractions with computerized tomography (CT) guidance is associated with unacceptable rates of grade 3-5 toxicity. Safe dose escalation can be facilitated by radiation delivery systems that utilize magnetic resonance image (MRI) guidance and on-table adaptive replanning. A growing body of literature describes promising efficacy and safety of ablative 5-fraction stereotactic MRI-guided adaptive radiation therapy (SMART) for LAPC compared to historical non-ablative outcomes. Based on these encouraging results, the LAP-ABLATE trial has been designed to test the hypothesis that ablative SMART improves OS. Methods: The LAP-ABLATE trial is a multi-institutional group sequential randomized phase III study for patients with LAPC. Patients are eligible after first receiving 4-6 months of (modified)FOLFIRINOX or gemcitabine/nab-paclitaxel with either stable or responding disease. Other key eligibility criteria include CA 19-9 <180 U/mL and no contraindication to undergoing MRI scans. Patients are randomized (1:2) to receiving no ablative SMART (arm A) versus ablative SMART (arm B), with subsequent systemic therapy or surgery being optional in both arms. Ablative SMART will be delivered using the MRIdian Linac, a 0.35 Tesla MRI-guided linear accelerator. The prescribed dose is 50 Gy to gross disease and 33 Gy to elective regions in 5 fractions using a simultaneous integrated boost (SIB). The primary objective is to compare 2-year OS with secondary objectives including assessment of LRC, distant metastasis free survival (DMFS), progression-free survival (PFS), quality of life (QOL), and toxicity. Randomization will be stratified by participating center, baseline CA 19-9 level and induction chemotherapy regimen. Target accrual is 267 patients (arm A: 89, arm B: 178). Discussion: The LAP-ABLATE trial is the first prospective randomized phase III study designed to compare OS in LAPC patients following induction systemic therapy randomized to with or without ablative 5-fraction RT. Citation Format: Michael D. Chuong, Jessica M. Frakes, Kathryn E. Mittauer, James Good, Josh Kim, Daniel Chang, Dae Won Kim, Stefanie Corradini, Luca Boldrini, Mokenge Malafa, Eileen O'Reilly. A multi-institutional randomized phase III trial of chemotherapy alone versus chemotherapy and ablative 5-fraction MRI-guided adaptive radiation therapy for locally advanced pancreatic cancer (LAP-ABLATE) [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr A005.