Metformin Hydrochloride and Aspirin in Treating Patients With Hormone-Dependent Prostate Cancer That Has Progressed After Surgery or Radiation Therapy

PRIMARY OBJECTIVES: I. To determine the effect of metformin (metformin hydrochloride) and aspirin on the change in prostate-specific antigen (PSA) progression in men with rising PSA after definitive therapy for localized prostate cancer and stable disease during a run-in period with the study regimen. SECONDARY OBJECTIVES: I. To determine the feasibility and safety of administering metformin and aspirin. II. To determine the effect of metformin and aspirin on PSA levels and the serum obesity-related prostate cancer (PCa) biomarkers (insulin, insulin-like growth factor \[IGF\]-1, interleukin \[IL\]-1beta, IL-6, and tumor necrosis factor \[TNF\]-alpha). OUTLINE: RUN-IN STAGE: Patients receive metformin hydrochloride orally (PO) twice daily (BID) and aspirin PO once daily (QD) for 4 months. Patients with disease progression (PSA increase of \> 50% and minimum of 2ng/ml rise in PSA) come off study. Patients achieving disease response (\>25% decline in PSA) continue to receive study agents in the absence of disease progression or unacceptable disease. Patients with stable disease continue on to the randomized study regimen. RANDOMIZATION STAGE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive metformin hydrochloride PO BID and aspirin PO QD for 6 months in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive metformin hydrochloride placebo PO BID and aspirin placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12-16 weeks for 1 year.