Stereotactic Body Radiation Therapy and Metformin Hydrochloride in Treating Patients with Borderline-Resectable or Locally-Advanced Pancreatic Cancer

Inclusion Criteria

• Subjects must be able to provide written informed consent
• Histologically and/or cytologically confirmed adenocarcinoma of the pancreas, clinical stage T1-4, N0-1, M0
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Hemoglobin >= 9.0 g/dl (within 14 days of enrollment)
• Alkaline phosphatase < 3 x upper limit of normal (ULN) (within 14 days of enrollment)
• Albumin > 2.5 g/dL (within 14 days of enrollment)
• Absolute neutrophil count >= 1500/mm^3 (within 14 days of enrollment)
• Platelet count >= 75,000/mm^3 (within 14 days of enrollment)
• Total bilirubin < 1.5 x upper limit of normal (ULN) (within 14 days of enrollment)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x institutional upper limit of normal (within 14 days of enrollment)
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 x institutional upper limit of normal (within 14 days of enrollment)
• Creatinine =< 1.5 (within 14 days of enrollment)
• Borderline-resectable or not surgically resectable pancreatic cancer (based upon impression of the surgical oncologist, in conjunction with radiologic consultations) as defined per the Alliance consensus: * Borderline-resectable ** An interface between the primary tumor and superior mesenteric vein (SMV)/portal vein measuring 180 degrees or greater of the circumference of the vein wall ** Short-segment occlusion of the SMV/portal vein but with suitable vessel proximal and distal to the obstruction to allow safe resection and reconstruction ** Short-segment interface (of any degree) between the tumor and the hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and arterial reconstruction ** An interface between the tumor and the superior mesenteric artery (SMA) or celiac trunk measuring less than 180 degrees of the circumference of the artery wall * Not surgically resectable due to one or more of the following things: ** Patient is not a surgical candidate due to medical comorbidities and/or poor performance status ** Patient elects not to undergo surgical therapy ** Patient has locally-advanced pancreatic cancer based on having one of the following: *** Encasement of the SMA/celiac artery (> 180 degrees) *** Involvement of the SMV/portal vein without options for reconstruction *** Aortic invasion or encasement
• The effects of metformin on the developing human fetus are unknown; for this reason and because metformin as well as other therapeutic agents used in this study are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) 6 weeks prior to study entry, for the duration of study participation and for 6 months after completing treatment; should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately.
• Patients previously treated with chemotherapy are eligible unless they have evidence of local or distant disease progression; patients must have completed their last cycle of chemotherapy at least two weeks prior to study enrollment
• Patients currently taking metformin are eligible for participation
• Women of child-bearing potential and male patients who are sexually-active must agree to use effective methods of birth control throughout protocol treatment
• Patients must not have poorly-controlled diarrhea (no more than 4 loose stools per day); patients may be reconsidered for the study if the diarrhea resolves

Exclusion Criteria

• Evidence of gross duodenal invasion, gastric outlet obstruction on endoscopy report
• Gastrointestinal perforation or intra-abdominal abscess (< 3 months); recent (< 3 months) gastrointestinal (GI) bleeding from gastric or duodenal ulcer (patients with hemorroidal bleeding will be allowed on the protocol)
• Systemic collagen vascular disease including scleroderma or systemic lupus erythematosus (SLE); rheumatoid arthritis is eligible
• Serious active infection requiring intravenous (IV) antibiotics
• Conditions leading to inadequate gastrointestinal tract absorption as determined by the treating physician and/or investigator
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Poorly-controlled diarrhea (> 4 loose bowel movement [BM]/day without use of anti-motility agents) within 7 days of study enrollment; patients may be reconsidered for the study if the diarrhea resolves
• Comorbid conditions that, in the opinion of the investigator, would complicate safety or compliance such as current substance abuse
• Patients who are pregnant or lactating
• Patients who are unwilling or unable to comply with study and/or follow-up procedures
• Treatment for other carcinomas within the last two years, except cured non-melanoma skin cancer, curatively treated in-situ cervical cancer, or localized prostate cancer with stable prostate-specific antigen (PSA)
• Multi-focal pancreatic lesions concerning for cancer