Clinical trial NCT01864096: The Metformin Active Surveillance Trial (MAST) Study
Official title: A Randomized, Double-Blind, Placebo-Controlled Trial of Metformin in Reducing Progression Among Men on Expectant Management for Low Risk Prostate Cancer: The MAST (Metformin Active Surveillance Trial) Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: localized
prostate
cancer
metformin
active surveillance
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2013-05-29
Enrollment: 408
Sex: MALE
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to see if metformin can delay the time to progression in men with low risk prostate cancer when compared to a placebo.


Eligibility criteria: Inclusion Criteria:

1. Must be male \> 18 and \< 80 years of age
2. Have biopsy proven, low-risk, localized prostate cancer choosing expectant management as primary treatment ≤ 1year. \[For the purposes of assessing subject eligibility a diagnostic biopsy must have included at least 10 cores, ≤1/3 of total number of cores sampled and \< 50% of any one core positive) and must have been obtained within 6 months of screening\]. Initial diagnosis of T1a/T1b obtained during a TURP is not allowed
3. Gleason score ≤ 6 \[Gleason pattern 4 or above must not be present on any biopsy (initial or entry)\]
4. Clinical stage T1c-T2a
5. Serum PSA ≤10 ng/mL (prior to biopsy)
6. Life expectancy greater than 5 years, as judged by the treating clinician/urologist
7. Able to swallow and retain oral medication
8. Hemoglobin A1c \< 6.5%
9. Able and willing to participate in the full 3 years of the study
10. Able to understand instructions related to study procedures
11. Able to read and write (health outcome questionnaires are self-administered), understand instructions related to study procedures and give written informed consent

Exclusion Criteria:

1. Subject that has ever been treated for prostate cancer with any of the following:

   * Radiotherapy (external beam or brachytherapy)
   * Chemotherapy
   * Hormonal therapy (e.g., megestrol, medoxyprogesterone, cyproterone)
   * Oral glucocorticoids
   * GnRH analogues (e.g., leuprolide, goserelin, degarelix)
2. Current and/or previous use of the following medications:

   * Use of 5α-reductase inhibitors (eg. Finasteride, Dutasteride) within the past 6 months of screening
   * Drugs with antiandrogenic properties (e.g., flutamide, bicalutamide, ketoconazole, progestational agents) within 6 months prior to screening
3. Previous or current diagnosis of type 1 or type 2 diabetes
4. Exposure to metformin within 12 months of screening
5. Planned or concurrent use of metformin hydrochloride, sulfonylureas, thiazolidinediones, or insulin for any reason
6. Known hypersensitivity or intolerance to metformin hydrochloride
7. Any condition associated with increased risk of metformin hydrochloride-associated lactic acidosis (e.g. congestive heart failure defines as NYHA class III or IV, history of any type of acidosis, habitual intake of ≥ 4 alcoholic beverages per day)
8. Subject has had prior prostatic surgery including TUNA, TURP, TUIP, laser treatment, thermotherapy, balloon dilatation, prosthesis, and ultrasound ablation within 3 months of screening
9. Participation in any investigational or marketed drug trial within 30 days prior to screening or anytime during the study period. This includes any interventional or exercise trials
10. Any unstable serious co-existing medical condition(s) including, but not limited to, myocardial infarction, coronary bypass surgery, unstable angina, cardiac arrhythmias, clinically evident congestive heart failure, or cerebrovascular accident within 6 months prior to Screening visit
11. Abnormal liver function test:

    * Total bilirubin \> 1.8 X institutional upper limit of normal (ULN)
    * Aspartate aminotransferase (AST) \> 1.8 X institutional ULN
    * Alanine aminotransferase (ALT) \> 1.8 X institutional ULN
    * Alkaline phosphatase (ALP) \> 1.8 X institutional ULN
12. Serum creatinine \> 1.8 X ULN
13. History of other malignancies, with the exception of adequately treated nonmelanoma skin cancer, stage I melanoma, NMIBC or other solid tumors curatively treated with no evidence of disease for at least 5 years
14. History or current evidence of substance abuse, as defined in DSM-IV, within 12 months of screening
15. History of any illness (including psychiatric) that, in the opinion of the investigator, might confound the results of the study or pose additional risk to the subject
16. No other concurrent metformin hydrochloride, sulfonylureas, thiazolidinediones, or insulin for any reason

Primary outcomes:
measure: Time to progression
timeFrame: 3 years
Secondary outcomes:
measure: Time to primary therapy for prostate cancer
timeFrame: 3 years
measure: Time to pathological progression
timeFrame: 3 years
measure: Change from baseline in disease-related patient anxiety
timeFrame: 3 years
measure: Change from baseline in decisional satisfaction and decisional conflict
timeFrame: 3 years
measure: Change from baseline in prostate cancer diagnosis at repeat biopsy
timeFrame: 3 years
measure: Change in Gleason Score at repeat biopsy
timeFrame: 3 years
measure: Change in clinical stage of prostate cancer based on digital rectal examination
timeFrame: 3 years
measure: Assess the prognostic and predictive value of prostate cancer biomarkers
timeFrame: 3 years
measure: To determine the safety and incidence of (serious) adverse events from the administration of 36 months of metformin to men with early stage prostate cancer
timeFrame: 3 years
Other outcomes:
Locations:
city: Winnipeg
country: Canada
facility: Manitoba Cancer Care Centre
state: Manitoba
city: Halifax
country: Canada
facility: CDHA - Victoria Site
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Institute of Urology-St .Joseph's Healthcare
state: Ontario
city: Kingston
country: Canada
facility: Centre for Appled Urologic Research, Kingston General Hospital
state: Ontario
city: London
country: Canada
facility: London Health Sciences Centre-Victoria Hospital
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Research Institute (The Ottawa Hospital)
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Research Institute
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Centre L'Hopitalie de l'Universite de Montreal
state: Quebec
city: Montreal
country: Canada
facility: MUHC - Montreal General Hospital
state: Quebec
city: Sherbrooke
country: Canada
facility: Centre de Recherche du CHUS
state: Quebec
city: Edmonton
country: Canada
facility: Alberta Urology Institute
Study officials:
affiliation: University Health Network: Department of Surgical Oncology (Urology)
name: Neil Fleshner, MD, MPH, FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: University Health Network: Department of Surgical Oncology (Urology)
name: Anthony Joshua, MD
role: PRINCIPAL_INVESTIGATOR
References: