Metformin Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01433913
First received: September 9, 2011
Last updated: July 28, 2014
Last verified: May 2014

September 9, 2011
July 28, 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 ]
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.
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 ]
    Descriptive statistics will be performed on prostate tissue metformin concentrations within each intervention group. Little if any metformin is expected in the placebo group. Data between the two study groups will be compared using a two-group t-test at a two-sided 0.05 level of significance. The means (and 95% confidence intervals) and distribution of actual values will be reported. Linear regression will be performed to the post-intervention metformin concentration levels to adjust for demographics and duration on intervention. Logistic regression will also be performed.
  • 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 ]
    Changes in a serum biomarker (from baseline to post-intervention) and secondary tissue endpoints will be compared between intervention groups using a t-test. If the distributions are not normally distributed, a non-parametric rank-sum test will be utilized. Correlations among the biomarkers and between postintervention metformin levels and changes in biomarker levels, will be explored (using Pearson or Spearman Rank correlation coefficients). Plasma levels of metformin will also be compared between groups using a t-test and the correlation of plasma and prostate tissue levels will be examined.
  • 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 ]
    Changes in a serum biomarker (from baseline to post-intervention) and secondary tissue endpoints will be compared between intervention groups using a t-test. If the distributions are not normally distributed, a non-parametric rank-sum test will be utilized. Correlations among the biomarkers and between postintervention metformin levels and changes in biomarker levels, will be explored (using Pearson or Spearman Rank correlation coefficients). Plasma levels of metformin will also be compared between groups using a t-test and the correlation of plasma and prostate tissue levels will be examined.
  • 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 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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • 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.
 
Active, not recruiting
21
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
  • 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
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01433913
NCI-2012-00243, NCI-2012-00243, CDR0000712087, UARIZ-UAZ10-16-01, 11-0211-04, UAZ10-16-01, N01CN35158, P30CA023074
Yes
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Robert Krouse Arizona Cancer Center - Tucson
National Cancer Institute (NCI)
May 2014

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