NCT01433913

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
20

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Nov 2011

Geographic Reach
1 country

3 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

September 9, 2011

Completed
5 days until next milestone

First Posted

Study publicly available on registry

September 14, 2011

Completed
2 months until next milestone

Study Start

First participant enrolled

November 1, 2011

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2014

Completed
1.1 years until next milestone

Results Posted

Study results publicly available

May 15, 2015

Completed
Last Updated

January 10, 2018

Status Verified

December 1, 2017

Enrollment Period

2.4 years

First QC Date

September 9, 2011

Results QC Date

April 29, 2015

Last Update Submit

December 12, 2017

Conditions

Adenocarcinoma of the ProstateRecurrent Prostate CancerStage I Prostate CancerStage IIA Prostate CancerStage IIB Prostate Cancer

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (13)

  • Prostate Tissue Metformin Concentration Levels as Assessed by Liquid Chromatography Tandem Mass Spectrometry

    12 weeks

  • Apoptosis Levels in the Prostatectomy Tissue as Assessed by IHC of Cleaved Caspase 3

    12 weeks

  • Cell Cycle Regulation in the Prostatectomy Tissue as Assessed by IHC of Cyclin D1

    12 weeks

  • mTOR Regulation in the Prostatectomy Tissue as Assessed by IHC of Phospho-p70 S6 Kinase (p-p70S6K)

    12 weeks

  • Angiogenesis in the Prostatectomy Tissue as Assessed by IHC of CD34

    12 weeks

  • +8 more secondary outcomes

Study Arms (2)

Arm I (metformin hydrochloride)

EXPERIMENTAL

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

Drug: metformin hydrochlorideOther: laboratory biomarker analysis

Arm II (placebo)

PLACEBO COMPARATOR

Patients receive placebo PO QD for 4-12 weeks.

Other: placeboOther: laboratory biomarker analysis

Interventions

metformin hydrochlorideDRUG

Given PO

Also known as: Glucophage
Arm I (metformin hydrochloride)
placeboOTHER

Given PO

Also known as: PLCB
Arm II (placebo)
laboratory biomarker analysisOTHER

Correlative studies

Arm I (metformin hydrochloride)Arm II (placebo)

Eligibility Criteria

Age18 Years+
Sexmale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

Arizona Cancer Center - Tucson

Tucson, Arizona, 85724-5024, United States

Location

University of Arizona Health Sciences Center

Tucson, Arizona, 85724, United States

Location

University of Southern California/Norris Cancer Center

Los Angeles, California, 90033, United States

Location

Related Publications (2)

  • 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.

    PMID: 32994091DERIVED

  • 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.

    PMID: 28692586DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic Chemicals

Results Point of Contact

Title
Dr. Sherry Chow
Organization
University of Arizona
schow@azcc.arizona.edu
520-626-3358

Study Officials

  • Robert Krouse

    Arizona Cancer Center - Tucson

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 9, 2011

First Posted

September 14, 2011

Study Start

November 1, 2011

Primary Completion

April 1, 2014

Study Completion

April 1, 2014

Last Updated

January 10, 2018

Results First Posted

May 15, 2015

Record last verified: 2017-12

Locations

US(3)