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