Phase II Study of Metformin in a Pre-prostatectomy Prostate Cancer Cohort
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
II. To determine the effect of metformin intervention on apoptosis and angiogenesis in the
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
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
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.
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment
Cell proliferation in the prostatectomy tissue as assessed by Ki67 expression using immunohistochemistry (IHC)
University of Arizona Health Sciences Center
United States: Food and Drug Administration
|University of Arizona Health Sciences Center||Tucson, Arizona 85724|
|University of Southern California||Los Angeles, California 90033|