The Metformin Active Surveillance Trial (MAST) Study

Exclusion Criteria

• •1. Subject that has ever been treated for prostate cancer with any of the following:
• •* Radiotherapy (external beam or brachytherapy)
• •* Chemotherapy
• •* Hormonal therapy (e.g., megestrol, medoxyprogesterone, cyproterone)
• •* Oral glucocorticoids
• •* GnRH analogues (e.g., leuprolide, goserelin, degarelix)
• •2. Current and/or previous use of the following medications:
• •* Use of 5α-reductase inhibitors (eg. Finasteride, Dutasteride) within the past 6 months of screening
• •* Drugs with antiandrogenic properties (e.g., flutamide, bicalutamide, ketoconazole, progestational agents) within 6 months prior to screening
• •3. Previous or current diagnosis of type 1 or type 2 diabetes
• •4. Exposure to metformin within 12 months of screening
• •5. Planned or concurrent use of metformin hydrochloride, sulfonylureas, thiazolidinediones, or insulin for any reason
• •6. Known hypersensitivity or intolerance to metformin hydrochloride
• •7. Any condition associated with increased risk of metformin hydrochloride-associated lactic acidosis (e.g. congestive heart failure defines as NYHA class III or IV, history of any type of acidosis, habitual intake of ≥ 4 alcoholic beverages per day)
• •8. Subject has had prior prostatic surgery including TUNA, TURP, TUIP, laser treatment, thermotherapy, balloon dilatation, prosthesis, and ultrasound ablation within 3 months of screening
• •9. 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
• •10. Any unstable serious co-existing medical condition(s) including, but not limited to, myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within 6 months prior to Screening visit
• •11. Abnormal liver function test:
• •* Total bilirubin \> 1.8 X institutional upper limit of normal (ULN)
• •* Aspartate aminotransferase (AST) \> 1.8 X institutional ULN
• •* Alanine aminotransferase (ALT) \> 1.8 X institutional ULN
• •* Alkaline phosphatase (ALP) \> 1.8 X institutional ULN
• •12. Serum creatinine \> 1.8 X ULN
• •13. History of other malignancies, with the exception of adequately treated nonmelanoma skin cancer, stage I melanoma, NMIBC or other solid tumors curatively treated with no evidence of disease for at least 5 years
• •14. History or current evidence of substance abuse, as defined in DSM-IV, within 12 months of screening
• •15. 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
• •16. No other concurrent metformin hydrochloride, sulfonylureas, thiazolidinediones, or insulin for any reason