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Metformin Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery

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ClinicalTrials.gov Identifier: NCT01433913
Recruitment Status : Completed
First Posted : September 14, 2011
Results First Posted : May 15, 2015
Last Update Posted : January 10, 2018
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Adenocarcinoma of the Prostate Recurrent Prostate Cancer Stage I Prostate Cancer Stage IIA Prostate Cancer Stage IIB Prostate Cancer Drug: metformin hydrochloride Other: placebo Other: laboratory biomarker analysis Phase 2

Detailed Description:


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 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  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase II Study of Metformin in a Pre-prostatectomy Prostate Cancer Cohort
Study Start Date : November 2011
Primary Completion Date : April 2014
Study Completion Date : April 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Prostate Cancer
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Arm I (metformin hydrochloride)
Patients receive extended-release metformin hydrochloride PO QD for 4-12 weeks.
Drug: metformin hydrochloride
Given PO
Other Name: Glucophage
Other: laboratory biomarker analysis
Correlative studies
Placebo Comparator: Arm II (placebo)
Patients receive placebo PO QD for 4-12 weeks.
Other: placebo
Given PO
Other Name: PLCB
Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Cell Proliferation in the Prostatectomy Tissue as Assessed by Ki67 Expression Using Immunohistochemistry (IHC) [ Time Frame: 12 weeks ]
    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.

Secondary Outcome Measures :
  1. Prostate Tissue Metformin Concentration Levels as Assessed by Liquid Chromatography Tandem Mass Spectrometry [ Time Frame: 12 weeks ]
  2. Apoptosis Levels in the Prostatectomy Tissue as Assessed by IHC of Cleaved Caspase 3 [ Time Frame: 12 weeks ]
    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

  3. Cell Cycle Regulation in the Prostatectomy Tissue as Assessed by IHC of Cyclin D1 [ Time Frame: 12 weeks ]
  4. mTOR Regulation in the Prostatectomy Tissue as Assessed by IHC of Phospho-p70 S6 Kinase (p-p70S6K) [ Time Frame: 12 weeks ]
  5. Angiogenesis in the Prostatectomy Tissue as Assessed by IHC of CD34 [ Time Frame: 12 weeks ]
  6. AMPK Activation in the Prostatectomy Tissue as Assessed by IHC of p-AMPK [ Time Frame: 12 weeks ]
  7. Cell Cycle Regulation in the Prostatectomy Tissue as Assessed by IHC of Retinoblastoma Protein Phosphorylation (p-pRb) [ Time Frame: 12 weeks ]
  8. Changes in Serum PSA [ Time Frame: Baseline and 12 weeks ]
  9. Changes in Serum Fasting Insulin [ Time Frame: Baseline and 12 weeks ]
  10. Changes in Serum IGF-1/IGFBP-3 [ Time Frame: Baseline and 12 weeks ]
  11. Changes in Serum Testosterone [ Time Frame: Baseline and 12 weeks ]
  12. Changes in Serum SHBG [ Time Frame: Baseline and 12 weeks ]
  13. Changes in Serum Fasting Glucose [ Time Frame: Baseline and 12 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01433913

United States, Arizona
Arizona Cancer Center - Tucson
Tucson, Arizona, United States, 85724-5024
University of Arizona Health Sciences Center
Tucson, Arizona, United States, 85724
United States, California
University of Southern California/Norris Cancer Center
Los Angeles, California, United States, 90033
Sponsors and Collaborators
National Cancer Institute (NCI)
Principal Investigator: Robert Krouse Arizona Cancer Center - Tucson

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01433913     History of Changes
Obsolete Identifiers: NCT01528527
Other Study ID Numbers: NCI-2012-00243
NCI-2012-00243 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
11-0211-04 ( Other Identifier: Arizona Cancer Center - Tucson )
UAZ10-16-01 ( Other Identifier: DCP )
N01CN35158 ( U.S. NIH Grant/Contract )
P30CA023074 ( U.S. NIH Grant/Contract )
First Posted: September 14, 2011    Key Record Dates
Results First Posted: May 15, 2015
Last Update Posted: January 10, 2018
Last Verified: December 2017

Additional relevant MeSH terms:
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Hypoglycemic Agents
Physiological Effects of Drugs