CClinicalTrials.gg
Sign In
TerminatedNCT00881725ANIMATEUpdated Jun 19, 2012

A Study of Pre-operative Metformin in Prostate Cancer

A Phase 2 interventional study of Metformin in Prostate Cancer, sponsored by University Health Network, Toronto. Terminated at 1 site in Canada. Open to male participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2012-06-19.

Sponsored by University Health Network, Toronto · Phase 2, Interventional, and Treatment

Why this study was terminated
Slow Accrual
Phase
Phase 2
Study type
Interventional
Enrollment
24
Allocation
Not applicable
Ages
18 Years to 75 Years
Sex
Male
01

Study summary

This study will investigate the effect of neoadjuvant metformin therapy in the inhibition of growth and proliferation of prostate cancer cells prior to radical prostatectomy.

Read the detailed description

Prostate cancer is the most commonly diagnosed malignancy in men in North America, with close to a quarter of a million cases diagnosed in 2007 alone (Joshua et al, 2007). The activation of the PTEN/ AKT pathway is thought to be of importance in prostatic carcinogenesis as it correlates with a poor prognosis (Yoshimoto et al, 2007) (Schmitz et al, 2007). Components of this cellular pathway have pleiotropic targets including the mTOR complex. In model systems, tumours exhibiting activation of PI3K/AKT kinase are sensitive to mTOR inhibitors.

Metformin (1,1-dimethylbiguanide hydrochloride) belongs to the biguanide class of oral hypoglycaemic agents and is a commonly prescribed medication for a number of conditions. It is the first-line drug of choice for the treatment of type 2 diabetes. Its mechanism of action is thought to be the primary inhibition of hepatic glucose output through inhibition of gluconeogenesis. Subsequently, metformin causes a decline in the circulating insulin level (Hundal et al, 2000).

Metformin causes inhibition of the mTOR complex. The mTOR complex is primarily inhibited through activation of AMPK (a component of the PTEN/AKT pathway). Metformin causes reduced hepatic glucose output leading to decreased levels of circulating insulin which causes the secondary inhibition of the mTOR complex. Metformin has also been shown to inhibit cyclin D1 expression and retinoblastoma protein (Rb) phosphorylation. Inhibition of Cyclin D1 and Rb phosphorylation cause inhibition of G1/S phase transition of the cell cycle. This results in the inhibition of cell proliferation (Matsushime et al, 1994).

This study will investigate the effect of neoadjuvant metformin therapy in the inhibition of growth and proliferation of prostate cancer cells prior to radical prostatectomy.

02

Conditions studied

  • Prostate Cancer

Browse trials for

Keywords

  • Metformin
  • Prostate Cancer
  • Radical Prostatectomy
  • Neoadjuvant Intervention
  • PTEN/AKT Pathway
  • Tumour Expression
  • Ki67 Expression
03

In context

Prostatic Neoplasms

6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.

This study's enrollment of 24 is below the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.

Browse Prostatic Neoplasms studies →

Lead sponsor

University Health Network, Toronto is the lead sponsor of 1,411 studies on the registry; 292 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 3 (18%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
Male
Accepts healthy volunteers
No

Inclusion criteria

    1. Patients with histologically confirmed prostate cancer involving at least 20% of at least one unfragmented biopsy core;
  2. Over the age of 18 and under the age of 75;
  3. Ability to read and understand the consent form, either alone or with the aid of a translator
  4. ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%);
  5. Patients must have their TRUS biopsy performed at UHN (or at an outside institution if tissue accession can be arranged) in the last 3 months;

  6. Patients must have normal organ and marrow function as defined by the following criteria:

    1. Absolute neutrophil count greater than or equal to 1,500/uL
    2. Platelets greater than or equal to 100,000/uL
    3. Total bilirubin less than or equal to 1.5 X institutional ULN
    4. AST(SGOT)/ALT(SGPT) less than or equal to 1.5 X institutional ULN
    5. Creatinine less than or equal to 1.4 X institutional ULN

Exclusion criteria

Exclusion Criteria:

  1. Patients who on initial assessment are found to be on treatment with any drug used for the treatment of any form of diabetes, or patients that begin treatment for any form of diabetes during the course of the study;
  2. Patients may not be receiving any other investigational, herbal or anticancer agents while on study;
  3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure (NYHA Class 3 or greater), cirrhosis with a Child-Pugh level of B or greater or evidence of cardiac dysfunction, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease, clinically significant gastrointestinal conditions (e.g. Crohns disease, ulcerative colitis), COPD or psychiatric illness/social situations that would limit compliance with study requirements;
  4. Active malignancy at any other site excluding squamous cell or basal cell carcinomas of the skin
  5. Radiotherapy within the past 4 weeks;
  6. Patients with a current history of alcohol intake (>2 standard drinks/day) or binge drinking (5 or more drinks (male), or 4 or more drinks (female)) in one session of 1-3 hours;
  7. Past history of lactic acidosis or risk factors for lactic acidosis such as congestive heart failure (NYHA Class 3 or greater), hypoxia (resting PO2 \< 91%) or renal insufficiency (eGFR \< 60 mls/min)
  8. Patients taking systemic glucocorticoids or estrogenic compounds.
  9. Patients with known hypersensitivity or allergy to metformin or any of its excipients.
  10. Patients with a history of impaired liver or kidney function.
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
24 participants (actual)

Study arms

  • Experimental
    Metformin

    500mg t.i.d. for 4-12 weeks prior to Radical Prostatectomy

    Drug: Metformin

Interventions

  • DrugMetformin

    500mg tablets t.i.d. for 4-12 weeks prior to Radical Prostatectomy

06

What researchers measure

Primary outcomes

  1. Difference in Ki67 staining

    Time frame: Pre-Surgery

Secondary outcomes

  1. Other immunohistochemical assays: IR, IGF-1R, p70S6K, AMPK, MVD, Cleaved caspase 3, PTEN, c-Myc

    Time frame: Pre-Surgery

  2. Differences in measures of insulin resistance: waist/hip ratio, fasting blood glucose, post-prandial blood glucose, weight

    Time frame: Pre-Surgery, Post-Surgery

  3. Differences in PSA levels

    Time frame: Pre-Surgery, Post-Surgery

  4. Incidence of adverse events, serious adverse events, and grade 3-4 toxicities

    Time frame: Pre-Surgery, Post-Surgery

07

Study locations

1 site
  • University Health Network
    Toronto, Ontario M5G2M9, Canada
08

References and documents

Publications

  • Joshua AM, Evans A, Van der Kwast T, Zielenska M, Meeker AK, Chinnaiyan A, Squire JA. Prostatic preneoplasia and beyond. Biochim Biophys Acta. 2008 Apr;1785(2):156-81. doi: 10.1016/j.bbcan.2007.12.001. Epub 2007 Dec 8. PubMed 18166163 ↗
  • Yoshimoto M, Cunha IW, Coudry RA, Fonseca FP, Torres CH, Soares FA, Squire JA. FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome. Br J Cancer. 2007 Sep 3;97(5):678-85. doi: 10.1038/sj.bjc.6603924. Epub 2007 Aug 14. PubMed 17700571 ↗
  • Schmitz M, Grignard G, Margue C, Dippel W, Capesius C, Mossong J, Nathan M, Giacchi S, Scheiden R, Kieffer N. Complete loss of PTEN expression as a possible early prognostic marker for prostate cancer metastasis. Int J Cancer. 2007 Mar 15;120(6):1284-92. doi: 10.1002/ijc.22359. PubMed 17163422 ↗
  • Hundal RS, Krssak M, Dufour S, Laurent D, Lebon V, Chandramouli V, Inzucchi SE, Schumann WC, Petersen KF, Landau BR, Shulman GI. Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes. 2000 Dec;49(12):2063-9. doi: 10.2337/diabetes.49.12.2063. PubMed 11118008 ↗
  • Matsushime H, Quelle DE, Shurtleff SA, Shibuya M, Sherr CJ, Kato JY. D-type cyclin-dependent kinase activity in mammalian cells. Mol Cell Biol. 1994 Mar;14(3):2066-76. doi: 10.1128/mcb.14.3.2066-2076.1994. PubMed 8114738 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 19, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00881725
Lead sponsor
University Health Network, Toronto
Collaborators
Jewish General Hospital
First posted
Apr 15, 2009
Start date
Jun 2009
Primary completion
Mar 2011
Completion
Jun 2012
Last update
Jun 19, 2012

Study contacts

Anthony Joshua, M.D.
principal investigator · University Health Network, Toronto

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Jun 2012. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Prostatic Neoplasms→

Other studies from this sponsor

University Health Network, Toronto

Start the discussion