A Study of Pre-operative Metformin in Prostate Cancer

NCT00881725 | Terminated Phase 2 DMC

• 1 other identifier: PMH-ANIMATE-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Prostate Cancer

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Difference in Ki67 staining

  Pre-Surgery

Secondary Outcomes (4)

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

  Pre-Surgery

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

  Pre-Surgery, Post-Surgery

• Differences in PSA levels

  Pre-Surgery, Post-Surgery

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

  Pre-Surgery, Post-Surgery

Study Arms (1)

Metformin

EXPERIMENTAL

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

Drug: Metformin

Interventions

Metformin DRUG

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

Metformin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Patients with histologically confirmed prostate cancer involving at least 20% of at least one unfragmented biopsy core;
• Over the age of 18 and under the age of 75;
• Ability to read and understand the consent form, either alone or with the aid of a translator
• ECOG performance status less than or equal to 2 (Karnofsky greater than or equal to 60%);
• 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;
• Patients must have normal organ and marrow function as defined by the following criteria:
• Absolute neutrophil count greater than or equal to 1,500/uL
• Platelets greater than or equal to 100,000/uL
• Total bilirubin less than or equal to 1.5 X institutional ULN
• AST(SGOT)/ALT(SGPT) less than or equal to 1.5 X institutional ULN
• Creatinine less than or equal to 1.4 X institutional ULN

You may not qualify if:

• 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;
• Patients may not be receiving any other investigational, herbal or anticancer agents while on study;
• 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;
• Active malignancy at any other site excluding squamous cell or basal cell carcinomas of the skin
• Radiotherapy within the past 4 weeks;
• 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;
• 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)
• Patients taking systemic glucocorticoids or estrogenic compounds.
• Patients with known hypersensitivity or allergy to metformin or any of its excipients.
• Patients with a history of impaired liver or kidney function.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Jewish General Hospital: collaborator

Study Sites (1)

University Health Network

Toronto, Ontario, M5G2M9, Canada

Location

Related Publications (5)

• 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.

  PMID: 18166163 BACKGROUND

• 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.

  PMID: 17700571 BACKGROUND

• 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.

  PMID: 17163422 BACKGROUND

• 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.

  PMID: 11118008 BACKGROUND

• 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.

  PMID: 8114738 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Metformin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Anthony Joshua, M.D.

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 14, 2009
• First Posted: April 15, 2009
• Study Start: June 1, 2009
• Primary Completion: March 1, 2011
• Study Completion: June 1, 2012
• Last Updated: June 19, 2012

Record last verified: 2012-06

Locations

CA (1)