Metformin Hydrochloride and Aspirin in Treating Patients With Hormone-Dependent Prostate Cancer That Has Progressed After Surgery or Radiation Therapy
Condition: Recurrent Prostate Carcinoma; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer; Stage III Prostate Cancer
MeSH terms: Prostatic Neoplasms
Intervention: Aspirin; Laboratory Biomarker Analysis; Metformin Hydrochloride; Placebo; Placebo
Intervention description: Given PO; Correlative studies; Given PO; Given metformin hydrochloride placebo PO; Given aspirin placebo PO
Intervention MeSH terms: Aspirin; Metformin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 27.0
Sex: Male
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well metformin hydrochloride and aspirin work in
      treating patients with hormone-dependent prostate cancer that has progressed after surgery or
      radiation therapy. Metformin hydrochloride and aspirin may stop the growth of tumor cells by
      blocking some of the enzymes needed for cell growth. It is not yet known whether giving
      metformin hydrochloride and aspirin together can slow the growth of prostate cancer.
    

Eligibility criteria:

        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