Stereotactic Radiosurgery and Metformin in 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
* Alkaline phosphatase \< 3 x upper limit of normal (ULN)
* Albumin \> 2.5 g/dL
* Absolute neutrophil count ≥ 1500/mm\^3
* Platelet count ≥ 75,000/mm\^3
* Total bilirubin \< 1.5 x upper limit of normal (ULN)
* Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 2.5 x institutional upper limit of normal
* Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 2.5 x institutional upper limit of normal
* Creatinine ≤ 1.5
* Borderline-resectable or locally-advanced 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 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.
* 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
* Gastrointestinal perforation or intra-abdominal abscess (\< 3 months); recent (\< 3 months) gastrointestinal (GI) bleeding from gastric or duodenal ulcer
* 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 known human immunodeficiency virus (HIV) or 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.