Metformin Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery

This study is currently recruiting participants.
Verified March 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01433913
First received: September 9, 2011
Last updated: March 19, 2014
Last verified: March 2014

September 9, 2011
March 19, 2014
November 2011
April 2014   (final data collection date for primary outcome measure)
Cell proliferation in the prostatectomy tissue as assessed by Ki67 expression using immunohistochemistry (IHC) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
cellular abnormality in prostate tissue removed at surgery [ Time Frame: after 4-12 weeks of agent intervention ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01433913 on ClinicalTrials.gov Archive Site
  • 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 ]
  • metformin concentration in prostate tissue removed at surgery [ Time Frame: after 4-12 weeks of agent intervention ] [ Designated as safety issue: No ]
  • molecular changes in prostate tissue removed at surgery [ Time Frame: after 4-12 weeks of agent intervention ] [ Designated as safety issue: No ]
  • Blood hormones/proteins related to prostate cancer risk [ Time Frame: after 4-12 weeks of agent intervention ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Metformin Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery
Phase II Study of Metformin in a Pre-prostatectomy Prostate Cancer Cohort

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 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, IGF binding protein (BP)3, 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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • Adenocarcinoma of the Prostate
  • Recurrent Prostate Cancer
  • Stage I Prostate Cancer
  • Stage IIA Prostate Cancer
  • Stage IIB Prostate Cancer
  • Drug: metformin hydrochloride
    Given PO
    Other Name: Glucophage
  • Other: placebo
    Given PO
    Other Name: PLCB
  • Other: laboratory biomarker analysis
    Correlative studies
  • Experimental: Arm I (metformin hydrochloride)
    Patients receive extended-release metformin hydrochloride PO QD for 4-12 weeks.
    Interventions:
    • Drug: metformin hydrochloride
    • Other: laboratory biomarker analysis
  • Placebo Comparator: Arm II (placebo)
    Patients receive placebo PO QD for 4-12 weeks.
    Interventions:
    • Other: placebo
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
50
Not Provided
April 2014   (final data collection date for primary outcome measure)

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
  • Plan to undergo radiologic studies involving intravascular administration of iodinated contrast materials
  • 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
Male
18 Years and older
No
Not Provided
United States
 
NCT01433913
NCI-2012-00243, NCI-2012-00243, CDR0000712087, UARIZ-UAZ10-16-01, 11-0211-04, UAZ10-16-01, P30CA023074, N01CN35158
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Mitchell Sokoloff Arizona Cancer Center - Tucson
National Cancer Institute (NCI)
March 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP