Extended-Release Metformin for the Treatment of Prostate Cancer

Inclusion Criteria

• Have biopsy confirmed cancer of the prostate
• High risk surgical cohort: patients who have had radical prostatectomy and: * High risk based on surgical pathology (patients have any of the following: >= Gleason 8, positive surgical margins, extracapsular extension or seminal vesicle invasion) * Undetectable PSA (< 0.1 ng/mL)
• Rising PSA surgical cohort: patients who have had radical prostatectomy and: * Rising serum PSA for 3 time points taken at least 1 month apart * Calculated PSA-doubling time (PSA-DT) > 6 months * Unwilling or medically unfit for salvage radiation therapy
• Rising PSA radiation cohort: patients who have had radiation for prostate cancer and: * Rising serum PSA for 3 time points taken at least 1 month apart, following nadir PSA * Calculated PSA-DT > 6 months * Must be at least 18 months since last radiation treatment ** Subjects with prior prostatectomy followed by salvage radiation is acceptable
• Able to swallow and retain oral medication
• Able and willing to participate in the full 9 months of the study
• Able to understand instructions related to study procedures
• Able to read and write (health outcome questionnaires are self-administered), understand instructions related to study procedures and give written informed consent

Exclusion Criteria

• Metastatic disease (including lymph node metastasis, seen on pathologically or radiographically)
• PSA-DT =< 6 months
• Subject that has ever been treated for prostate cancer with any of the following: * Chemotherapy * Hormonal therapy (e.g., megestrol, medroxyprogesterone, cyproterone) * Oral glucocorticoids * Gonadotrophin releasing hormone (GnRH) analogues (e.g., leuprolide, goserelin, degarelix) ** Previous treatment with GnRH analogues is allowed after a wash out of at least one month and a return to normal serum testosterone levels
• Current and/or previous use of the following medications: * Use of 5 alpha-reductase inhibitors (e.g. finasteride, dutasteride) within 6 months prior to screening * Drugs with antiandrogenic properties (e.g., flutamide, bicalutamide, ketoconazole, progestational agents) within 6 months prior to screening
• Diagnosis of type 1 diabetes mellitus
• Exposure to metformin within 12 months prior to screening
• Planned or concurrent use of any oral or injectable diabetes drug
• Known hypersensitivity or intolerance to metformin
• Any condition associated with increased risk of metformin-associated lactic acidosis
• Participation in any investigational or marketed drug trial within 30 days prior to screening or anytime during the study period. This includes any interventional or exercise trials
• Any unstable serious coexisting medical condition(s) including, but not limited to, myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, cerebrovascular accident, or any condition deemed serious in the opinion of the investigator within 6 months prior to the screening visit
• History of megaloblastic anemia
• History of other malignancies, with the exception of adequately treated non-melanoma skin cancer, stage I melanoma, non-muscle invasive bladder urothelial carcinoma (NMIBC) or other solid tumors curatively treated with no evidence of disease for at least 5 years
• History or current evidence of substance abuse, as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), within 12 months of screening
• History of any illness (including psychiatric) that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the subject
• Total bilirubin > 2 x institutional upper limit of normal (2 x ULN)
• Aspartate aminotransferase (AST) > 2 x ULN
• Alanine aminotransferase (ALT) > 2 x ULN
• Alkaline phosphatase (ALP) > 2 x ULN
• Serum creatinine > 2 x ULN
• Hemoglobin A1c > 7.0%
• Glucose > 200 mg/dL (If glucose level is above 200 mg/dL, the subject will be advised to be seen by an endocrinologist before being deemed eligible for the trial)