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

Inclusion Criteria:

Patients with histologically proven prostate cancer treated with surgery, radiation, or the combination of surgery and radiation for prostate cancer (metastatic to regional lymph nodes) with resection of the nodes, who now has a rising PSA value after definitive local therapy, and no visible metastatic disease on conventional imaging studies
Patients must have undergone local treatment via prostatectomy or radiation therapy

Patients must have PSA progression after local treatment:

PSA values for patients after surgery (or surgery and salvage/adjuvant radiation) must be greater than or equal to 0.2 ng/mL, determined by two measurements, at least 1 month apart and at least 6 months after prostatectomy
PSA values for patients after radiation must be greater than or equal to 2.0 ng/ml greater than the nadir achieved after radiation, determined by two measurements at 1 month apart and at least 6 months after the radiation treatment is completed; (patients who received adjuvant or salvage radiation after prostatectomy must have PSA of greater than or equal to 0.2)
The first two PSA values, along with a third (study baseline) value must all be rising (i.e., there must be an overall rising trajectory, such that the third value cannot be lower than the first value)
PSA must be less than 50 ng/mL at study entry
PSA doubling time using the mkscc.org PSA doubling time calculator must be greater than 4 months
Baseline bone scan, chest x-ray and computed tomography (CT)/magnetic resonance imaging (MRI) of abdomen/pelvis demonstrating no metastatic disease
Estimated life expectancy of at least 6 months
Eastern Cooperative Oncology Group (ECOG) performance status =< 2
White blood cells (WBC) > 3500/ul
Absolute neutrophil count (ANC) > 1500/ul
Hemoglobin > 10 g/dl
Platelet count > 100,000/ul
Adequate renal function with estimated glomerular filtration rate (GFR) by Cockcroft Gault of greater than 40 ML per minute
Total bilirubin must be within 1.5 X the normal institutional limits; if total bilirubin is outside the normal institutional limits, assess direct bilirubin
The direct bilirubin must be within normal parameters
Transaminases (serum glutamic oxaloacetic transaminase [SGOT] and/or serum glutamate pyruvate transaminase [SGPT]) must be less than 2.5 X the institutional upper limit of normal
Patients must have a serum total testosterone level >= 150 ng/dL at the time of enrollment within 4 weeks prior to randomization
Patients must sign informed consent

Exclusion Criteria:

Serious concomitant systemic disorder that would compromise the safety of the patient or compromise the patient's ability to complete the study, at the discretion of the investigator
Patients may have received prior androgen deprivation therapy (ADT) in the neoadjuvant, adjuvant and/or salvage setting, but must be off therapy for at least 3 months and have a testosterone level > 150 ng/dl
Second primary malignancy except most situ carcinoma (e.g. adequately treated non-melanomatous carcinoma of the skin) or other malignancy treated at least 2 years previously with no evidence of recurrence
Patients with type II diabetes currently already on metformin
Patients taking aspirin for previously diagnosed cardiovascular disease
Patients who received aspirin or metformin within the past 28 days
Patients taking medications with known interactions with metformin or aspirin
Patients taking warfarin or platelet inhibitors
Patients requiring chronic use of nonsteroidal anti-inflammatory drugs (NSAIDS)
Other concurrent experimental or investigational drugs
Prior history of lactic acidosis or metabolic acidosis
Patients with history of gastrointestinal (GI) bleeding and peptic ulcer disease
Any unstable, serious co-existing medical conditions 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