Metformin Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery

NCT ID: NCT01433913

Last Updated: 2018-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-11-30
• Study Completion Date: 2014-04-30

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.

Detailed 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.

Conditions

Adenocarcinoma of the Prostate; Recurrent Prostate Cancer; Stage I Prostate Cancer; Stage IIA Prostate Cancer; Stage IIB Prostate Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Arm I (metformin hydrochloride)

Patients receive extended-release metformin hydrochloride PO QD for 4-12 weeks.

Group Type: EXPERIMENTAL

metformin hydrochloride

Intervention Type: DRUG

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Arm II (placebo)

Patients receive placebo PO QD for 4-12 weeks.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: OTHER

Given PO

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

metformin hydrochloride

Given PO

Intervention Type: DRUG

placebo

Given PO

Intervention Type: OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

Glucophage; PLCB

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Krouse

Role: PRINCIPAL_INVESTIGATOR

Arizona Cancer Center - Tucson

Locations

Arizona Cancer Center - Tucson

Tucson, Arizona, United States

University of Arizona Health Sciences Center

Tucson, Arizona, United States

University of Southern California/Norris Cancer Center

Los Angeles, California, United States

Countries

United States

References

Roy S, Malone S, Grimes S, Morgan SC. Impact of Concomitant Medications on Biochemical Outcome in Localised Prostate Cancer Treated with Radiotherapy and Androgen Deprivation Therapy. Clin Oncol (R Coll Radiol). 2021 Mar;33(3):181-190. doi: 10.1016/j.clon.2020.09.005. Epub 2020 Sep 29.

Reference Type: DERIVED

PMID: 32994091 (View on PubMed)

Nguyen MM, Martinez JA, Hsu CH, Sokoloff M, Krouse RS, Gibson BA, Nagle RB, Parnes HL, Cordova C, Chow HS. Bioactivity and prostate tissue distribution of metformin in a preprostatectomy prostate cancer cohort. Eur J Cancer Prev. 2018 Nov;27(6):557-562. doi: 10.1097/CEJ.0000000000000394.

Reference Type: DERIVED

PMID: 28692586 (View on PubMed)

Other Identifiers

NCI-2012-00243

Identifier Type: REGISTRY

Identifier Source: secondary_id

CDR0000712087

Identifier Type: -

Identifier Source: secondary_id

UARIZ-UAZ10-16-01

Identifier Type: -

Identifier Source: secondary_id

11-0211-04

Identifier Type: OTHER

Identifier Source: secondary_id

UAZ10-16-01

Identifier Type: OTHER

Identifier Source: secondary_id

N01CN35158

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA023074

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2012-00243

Identifier Type: -

Identifier Source: org_study_id

NCT01528527

Identifier Type: -

Identifier Source: nct_alias