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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
20
Arizona Cancer Center - Tucson
Tucson, Arizona, United States
University of Arizona Health Sciences Center
Tucson, Arizona, United States
University of Southern California/Norris Cancer Center
Los Angeles, California, United States
Cell Proliferation in the Prostatectomy Tissue as Assessed by Ki67 Expression Using Immunohistochemistry (IHC)
Data between the two study groups will be compared using a two-group t-test at a two-sided 0.05 level of significance. If the data are not normally distributed, a non-parametric rank-sum test will be utilized.
Time frame: 12 weeks
Prostate Tissue Metformin Concentration Levels as Assessed by Liquid Chromatography Tandem Mass Spectrometry
Time frame: 12 weeks
Apoptosis Levels in the Prostatectomy Tissue as Assessed by IHC of Cleaved Caspase 3
Average number of positively stained cells that exhibited nuclear fragmentation from five randomly selected high-power fields (40x) in the tumor region was calculated for each participant
Time frame: 12 weeks
Cell Cycle Regulation in the Prostatectomy Tissue as Assessed by IHC of Cyclin D1
Time frame: 12 weeks
mTOR Regulation in the Prostatectomy Tissue as Assessed by IHC of Phospho-p70 S6 Kinase (p-p70S6K)
Time frame: 12 weeks
Angiogenesis in the Prostatectomy Tissue as Assessed by IHC of CD34
Time frame: 12 weeks
AMPK Activation in the Prostatectomy Tissue as Assessed by IHC of p-AMPK
Time frame: 12 weeks
Cell Cycle Regulation in the Prostatectomy Tissue as Assessed by IHC of Retinoblastoma Protein Phosphorylation (p-pRb)
Time frame: 12 weeks
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Changes in Serum PSA
Time frame: Baseline and 12 weeks
Changes in Serum Fasting Insulin
Time frame: Baseline and 12 weeks
Changes in Serum IGF-1/IGFBP-3
Time frame: Baseline and 12 weeks
Changes in Serum Testosterone
Time frame: Baseline and 12 weeks
Changes in Serum SHBG
Time frame: Baseline and 12 weeks
Changes in Serum Fasting Glucose
Time frame: Baseline and 12 weeks