This trial is active, not recruiting.

Conditions adenocarcinoma of the prostate, recurrent prostate cancer, stage i prostate cancer, stage iia prostate cancer, stage iib prostate cancer
Treatments metformin hydrochloride, placebo, laboratory biomarker analysis
Phase phase 2
Sponsor National Cancer Institute (NCI)
Start date November 2011
End date April 2014
Trial size 21 participants
Trial identifier NCT01433913, 11-0211-04, CDR0000712087, N01CN35158, NCI-2012-00243, NCT01528527, P30CA023074, UARIZ-UAZ10-16-01, UAZ10-16-01


This randomized phase II trial studies how well metformin hydrochloride works compared to placebo in treating patients with prostate cancer undergoing surgery. Metformin hydrochloride may make some enzymes active. These enzymes may block other enzymes needed for cell growth and stop the growth of tumor cells.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Patients receive extended-release metformin hydrochloride PO QD for 4-12 weeks.
metformin hydrochloride Glucophage
Given PO
laboratory biomarker analysis
Correlative studies
(Placebo Comparator)
Patients receive placebo PO QD for 4-12 weeks.
placebo PLCB
Given PO
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Cell proliferation in the prostatectomy tissue as assessed by Ki67 expression using immunohistochemistry (IHC)
time frame: 12 weeks

Secondary Outcomes

Prostate tissue metformin concentration levels as assessed by liquid chromatography tandem mass spectrometry
time frame: 12 weeks
Comparison of apoptosis (cleaved caspase 3), angiogenesis (CD34), AMPK activation (p-AMPK), mTOR regulation (p-p70S6K), cell cycle regulation (cyclin D1and p-pRb) in the prostatectomy tissue between study groups as assessed by IHC
time frame: 12 weeks
Comparison of changes in serum PSA, fasting glucose, fasting insulin, IGF-1/IGFBP-3, testosterone, and SHBG between study groups as assessed by liquid chromatography-tandem mass spectrometry assay
time frame: Baseline and 12 weeks

Eligibility Criteria

Male participants at least 18 years old.

Inclusion Criteria: - Men will be eligible to this study if they are diagnosed with a histologically confirmed organ-confined adenocarcinoma of the prostate (PCa) treatable by prostatectomy and have a current PSA less than 50 ng/ml - Have not received chemotherapy and/or radiation for any malignancy (excluding non-melanoma skin cancer and cancers confined to organs with removal as only treatment) in the past 5 years - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Karnofsky >= 70%) - Leukocytes >= 3,000/uL - Absolute neutrophil count >= 1,500/uL - Platelets >= 100,000/uL - Total bilirubin =< 1.5 times institutional upper limits of normal (ULN) - Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 times institutional ULN - Creatinine within normal institutional limits - Willing to use adequate contraception (barrier method, abstinence, subject has had a vasectomy or partner is using effective birth control or is postmenopausal) for the duration of study participation - Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: - Type I or type II diabetic patients on treatment with any drug for diabetes or participants with fasting glucose >= 126 mg/dL - History of impaired liver or kidney function - Participants with a current history of high alcohol consumption (> 3 standard drinks/day) or binge drinking (5 or more drinks) in one session of 1-3 hours - History of lactic acidosis or at increased risk for lactic acidosis such as patients with unstable or acute congestive heart failure who are at risk of hypoperfusion with hypoxemia - Participants may not be receiving any other investigational agents - History of allergic reactions attributed to compounds of similar chemical composition to metformin - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements - History of acute or chronic metabolic acidosis - Concurrent use of cationic drugs (e.g., amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or vancomycin) - Concurrent use of non-study metformin or other biguanides

Additional Information

Official title Phase II Study of Metformin in a Pre-prostatectomy Prostate Cancer Cohort
Principal investigator Robert Krouse
Description PRIMARY OBJECTIVES: I. To determine the effect of 4-12 weeks of metformin (metformin hydrochloride) intervention on cell proliferation in the prostatectomy tissue. SECONDARY OBJECTIVES: I. To determine the effect of metformin intervention on prostate tissue bioavailability of metformin. II. To determine the effect of metformin intervention on apoptosis and angiogenesis in the prostatectomy tissue. III. To determine the effect of metformin intervention on potential molecular targets of metformin including activated protein kinase (AMPK) activation, mammalian target of rapamycin (mTOR) regulation, and cell cycle regulation in the prostatectomy tissue. IV. To determine the effect of metformin intervention on changes in systemic hormones and growth factors that have been shown to be modulated by metformin in other patient populations including fasting glucose, fasting insulin, insulin-like growth factor axis, testosterone, and sex hormone binding globulin (SHBG). V. To determine the effect of metformin intervention on changes in prostate-specific antigen (PSA) levels. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive extended-release metformin hydrochloride orally (PO) once daily (QD) for 4-12 weeks. ARM II: Patients receive placebo PO QD for 4-12 weeks. Patients in both arms undergo surgery one day after completion of treatment. After completion of study treatment, patients are followed up within 30 days of surgery.
Trial information was received from ClinicalTrials.gov and was last updated in August 2014.
Information provided to ClinicalTrials.gov by National Cancer Institute (NCI).