Stereotactic Radiosurgery and Metformin in Patients With Borderline-Resectable or Locally-Advanced Pancreatic Cancer

This is an open label pilot, single-center, non-randomized trial is designed to evaluate the tolerability and preliminary activity of the combination of stereotactic body radiation therapy (SBRT) with metformin for resectable and locally-advanced pancreatic/periampullary cancers. PRIMARY OBJECTIVES: The primary objectives of this study are to: 1\) To determine if the addition of metformin to SBRT adds minimal additional toxicity for patients with A). borderline-resectable or B). not surgically resectable pancreatic adenocarcinomas. SECONDARY OBJECTIVES: I. Evaluate the clinical/pathological response and resectability rates associated with these regimens. OUTLINE: Patients receive metformin hydrochloride orally (PO) daily or twice daily (BID) on days -11 to -1. Patients then undergo stereotactic radiosurgery 5 days a week for 5 weeks and receive concurrent metformin hydrochloride\* by mouth, two times a day for 5 weeks. Patients undergo laparotomy on week 6 (or weeks 5-7). ). Systemic therapy continues as soon as it is considered feasible by the treating physicians. \*NOTE: Metformin hydrochloride should be stopped 2 days before laparotomy. After completion of study treatment, patients are followed up every 3 months for 2 years.