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Adenocarcinoma of the ProstatePhase 2NCT01433913

Metformin Hydrochloride in Treating Patients With Prostate Cancer Undergoing Surgery

A Phase 2 study testing metformin hydrochloride and laboratory biomarker analysis in people with Adenocarcinoma of the Prostate and Recurrent Prostate Cancer, run by National Cancer Institute (NCI) at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
metformin hydrochloride and laboratory biomarker analysis
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
20 participants
Where
3 sitesUnited States
Study dates
Nov 2011to Apr 2014
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • University of Southern California/Norris Cancer Center

    Los Angeles, California, 90033

  • Arizona Cancer Center - Tucson

    Tucson, Arizona, 85724-5024

  • University of Arizona Health Sciences Center

    Tucson, Arizona, 85724

Other trials in United States

About this study

Official title: 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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the effect of 4-12 weeks of metformin (metformin hydrochloride) intervention on cell proliferation in the prostatectomy tissue.

SECONDARY OBJECTIVES:

  1. 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).

  1. 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.

Being tested
metformin hydrochloride, placebo, laboratory biomarker analysis
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • metformin hydrochlorideDrug

    Also called Glucophage

    Given PO

  • placeboOther

    Also called PLCB

    Given PO

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01433913
Study groupRoleWhat they receive
Arm I (metformin hydrochloride)ExperimentalPatients receive extended-release metformin hydrochloride PO QD for 4-12 weeks.
Receives: Drug: metformin hydrochloride; Other: laboratory biomarker analysis
Arm II (placebo)Placebo comparatorPatients receive placebo PO QD for 4-12 weeks.
Receives: Other: placebo; Other: laboratory biomarker analysis

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 12 weeks

Secondary outcomes (13)

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

    Measured: 12 weeks

  2. 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

    Measured: 12 weeks

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

    Measured: 12 weeks

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

    Measured: 12 weeks

  5. Angiogenesis in the Prostatectomy Tissue as Assessed by IHC of CD34

    Measured: 12 weeks

  6. AMPK Activation in the Prostatectomy Tissue as Assessed by IHC of p-AMPK

    Measured: 12 weeks

  7. Cell Cycle Regulation in the Prostatectomy Tissue as Assessed by IHC of Retinoblastoma Protein Phosphorylation (p-pRb)

    Measured: 12 weeks

  8. Changes in Serum PSA

    Measured: Baseline and 12 weeks

  9. Changes in Serum Fasting Insulin

    Measured: Baseline and 12 weeks

  10. Changes in Serum IGF-1/IGFBP-3

    Measured: Baseline and 12 weeks

  11. Changes in Serum Testosterone

    Measured: Baseline and 12 weeks

  12. Changes in Serum SHBG

    Measured: Baseline and 12 weeks

  13. Changes in Serum Fasting Glucose

    Measured: Baseline and 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Sep 2011 (estimated)
  2. Study startNov 2011
  3. Primary completionApr 2014
  4. Study completionApr 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01433913
Sponsor's protocol ID
NCI-2012-00243
Other IDs
NCI-2012-00243, CDR0000712087, UARIZ-UAZ10-16-01, 11-0211-04, UAZ10-16-01, N01CN35158, P30CA023074
Status last verified
Dec 2017
First submitted
9 Sep 2011
Last updated
10 Jan 2018
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 32994091

  • 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.

    PubMed 28692586

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing metformin hydrochloride and laboratory biomarker analysis in people with Adenocarcinoma of the Prostate and Recurrent Prostate Cancer, run by National Cancer Institute (NCI) at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 May 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Cell Proliferation in the Prostatectomy Tissue as Assessed by Ki67 Expression Using Immunohistochemistry (IHC) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01433913, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2018.

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