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Phase II Study of Metformin in a Pre-prostatectomy Prostate Cancer Cohort

Phase 2
18 Years
Open (Enrolling)
Adenocarcinoma of the Prostate, Recurrent Prostate Cancer, Stage I Prostate Cancer, Stage IIA Prostate Cancer, Stage IIB Prostate Cancer

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Trial Information

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
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.

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 prostate-specific antigen (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/μL

- Absolute neutrophil count >= 1,500/μL

- Platelets >= 100,000/μL

- Total bilirubin =< 1.5 times institutional upper limits of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic 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

- 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

- Plan to undergo radiologic studies involving intravascular administration of
iodinated contrast materials

- No concurrent use of cationic drugs (e.g., amiloride, digoxin, morphine,
procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, or

- History of acute or chronic metabolic acidosis

- Concurrent use of non-study metformin or other biguanides

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Outcome Measure:

Cell proliferation in the prostatectomy tissue as assessed by Ki67 expression using immunohistochemistry (IHC)

Outcome Time Frame:

12 weeks

Safety Issue:


Principal Investigator

Mitchell Sokoloff

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Arizona Health Sciences Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 2011

Completion Date:

Related Keywords:

  • Adenocarcinoma of the Prostate
  • Recurrent Prostate Cancer
  • Stage I Prostate Cancer
  • Stage IIA Prostate Cancer
  • Stage IIB Prostate Cancer
  • Adenocarcinoma
  • Adenocarcinoma, Mucinous
  • Prostatic Neoplasms



University of Arizona Health Sciences Center Tucson, Arizona  85724
University of Southern California Los Angeles, California  90033