Metformin Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery

Adenocarcinoma of the Prostate Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01433913
• Other study ID #: NCI-2012-00243
• Secondary ID: NCI-2012-00243CD
• Status: Completed
• Phase: Phase 2
• First received: September 9, 2011
• Last updated: December 12, 2017
• Start date: November 2011
• Est. completion date: April 2014

Study information

• Verified date: December 2017
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Other known NCT identifiers

• NCT01528527

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• metformin hydrochloride
Given PO

Other:
• placebo
Given PO
• laboratory biomarker analysis
Correlative studies

Locations

Country	Name	City	State
United States	University of Southern California/Norris Cancer Center	Los Angeles	California
United States	Arizona Cancer Center - Tucson	Tucson	Arizona
United States	University of Arizona Health Sciences Center	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 weeks
Secondary	Prostate Tissue Metformin Concentration Levels as Assessed by Liquid Chromatography Tandem Mass Spectrometry		12 weeks
Secondary	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	12 weeks
Secondary	Cell Cycle Regulation in the Prostatectomy Tissue as Assessed by IHC of Cyclin D1		12 weeks
Secondary	mTOR Regulation in the Prostatectomy Tissue as Assessed by IHC of Phospho-p70 S6 Kinase (p-p70S6K)		12 weeks
Secondary	Angiogenesis in the Prostatectomy Tissue as Assessed by IHC of CD34		12 weeks
Secondary	AMPK Activation in the Prostatectomy Tissue as Assessed by IHC of p-AMPK		12 weeks
Secondary	Cell Cycle Regulation in the Prostatectomy Tissue as Assessed by IHC of Retinoblastoma Protein Phosphorylation (p-pRb)		12 weeks
Secondary	Changes in Serum PSA		Baseline and 12 weeks
Secondary	Changes in Serum Fasting Insulin		Baseline and 12 weeks
Secondary	Changes in Serum IGF-1/IGFBP-3		Baseline and 12 weeks
Secondary	Changes in Serum Testosterone		Baseline and 12 weeks
Secondary	Changes in Serum SHBG		Baseline and 12 weeks
Secondary	Changes in Serum Fasting Glucose		Baseline and 12 weeks