Metformin Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery
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.
Adenocarcinoma of the Prostate
Recurrent Prostate Cancer
Stage I Prostate Cancer
Stage IIA Prostate Cancer
Stage IIB Prostate Cancer
Drug: metformin hydrochloride
Other: laboratory biomarker analysis
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Phase II Study of Metformin in a Pre-prostatectomy Prostate Cancer Cohort|
- Cell proliferation in the prostatectomy tissue as assessed by Ki67 expression using immunohistochemistry (IHC) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- Prostate tissue metformin concentration levels as assessed by liquid chromatography tandem mass spectrometry [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
|Study Start Date:||November 2011|
|Estimated Primary Completion Date:||November 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm I (metformin hydrochloride)
Patients receive extended-release metformin hydrochloride PO QD for 4-12 weeks.
Drug: metformin hydrochloride
Other Name: GlucophageOther: laboratory biomarker analysis
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO QD for 4-12 weeks.
Other Name: PLCBOther: laboratory biomarker analysis
I. To determine the effect of 4-12 weeks of metformin (metformin hydrochloride) intervention on cell proliferation in the prostatectomy tissue.
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 AMPK activation, 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 PSA (prostate-specific antigen) levels.
OUTLINE: Patients are stratified by whether or not the institution will provide fresh frozen tissue for measurement of tissue metformin hydrochloride concentrations. 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. Paraffin-embedded blocks or slides from tumor tissue samples from prostatectomy are collected for cell proliferation and biomarker studies by sensitive liquid chromatography-tandem mass spectrometric, and immunohistochemistry. Patients also undergo serum sample collection at baseline and after completion of study treatment for PSA, fasting glucose, fasting insulin, insulin-like growth factor (IGF-1, IGFBP3, and SHBG), testosterone, and SHBG by enzyme-linked immunosorbent assay (ELISA) and liquid chromatography-tandem mass spectrometry assay.
After completion of study treatment, patients are followed up within 30 days of surgery.
|United States, Arizona|
|University of Arizona Health Sciences Center||Recruiting|
|Tucson, Arizona, United States, 85724|
|Contact: Mitchell H. Sokoloff 520-626-6895 email@example.com|
|Principal Investigator: Mitchell H. Sokoloff|
|United States, California|
|University of Southern California||Recruiting|
|Los Angeles, California, United States, 90033-0804|
|Contact: Mike M. Nguyen 323-865-3041 Mike.Nguyen@med.usc.edu|
|Principal Investigator: Mike M. Nguyen|
|Principal Investigator:||Mitchell Sokoloff||University of Arizona Health Sciences Center|