Stereotactic Adaptive Radiation Therapy for Borderline Resectable or Locally Advanced Pancreatic Cancer to Minimize Gastrointestinal Toxicity (ARTIA-Pancreas): Protocol for a Single-Arm Prospective Trial

Background: Computed tomography (CT)-guided online stereotactic adaptive radiotherapy (CT-STAR) allows for ablative radiation doses to be delivered to selected patients with borderline resectable (BR) or locally advanced pancreatic cancer (LAPC) or unresectable pancreatic cancer. However, the use of CT-STAR to deliver an ablative dose to the pancreas while minimizing gastrointestinal (GI) side effects to reduce acute and late toxicity rates compared to historic controls has yet to be prospectively evaluated. Objective: The primary objective of this prospective, single-arm, multicenter phase 2 clinical trial (Adaptive Radiation Therapy Individualized Approach [ARTIA]-Pancreas) is to evaluate the rate of acute grade 3+ GI toxicity in patients with BR/LAPC treated with ablatively dosed CT-STAR compared to historical controls. Methods: Patients with histologically or cytologically confirmed BR, locally advanced, or medically inoperable pancreatic adenocarcinoma are eligible for participation. Consenting and eligible patients will be treated with CT-STAR, delivering 5 fractions over 1 to 2 weeks with daily adaptation based on anatomic changes observed with onboard cone beam CT imaging. The primary end point of this trial is the rate of acute patient-reported grade 3+ treatment-related GI toxicities, assessed at 90 days post CT-STAR and compared to a historical control rate of 20%. The key powered secondary end point is the rate of long-term patient-reported grade 3+ treatment-related GI toxicities, evaluated at 12 months post CT-STAR and compared to a historical control rate of 25%. Additional secondary end points include overall survival, local (in-field) control rates, and distant progression-free survival at 1 and 2 years post CT-STAR. Results: Study completion is anticipated in February 2029, and the final study results will be published upon completion of the study. Conclusions: ARTIA-Pancreas represents the first prospective phase 2 clinical trial to evaluate whether CT-STAR can reduce the rate of acute patient-reported GI toxicities in patients with BR/LAPC compared to historical controls. Findings from this clinical trial will provide evidence for safely and effectively incorporating ablatively dosed adaptive radiotherapy into treatment regimens for this population.