The Metformin Active Surveillance Trial (MAST) Study

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be male > 18 and < 80 years of age 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 Gleason score ≤ 6 [Gleason pattern 4 or above must not be present on any biopsy (initial or entry)] Clinical stage T1c-T2a Serum PSA ≤10 ng/mL (prior to biopsy) Life expectancy greater than 5 years, as judged by the treating clinician/urologist Able to swallow and retain oral medication Hemoglobin A1c < 6.5% Able and willing to participate in the full 3 years of the study Able to understand instructions related to study procedures Able to read and write (health outcome questionnaires are self-administered), understand instructions related to study procedures and give written informed consent Exclusion Criteria: 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) 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 Previous or current diagnosis of type 1 or type 2 diabetes Exposure to metformin within 12 months of screening Planned or concurrent use of metformin hydrochloride, sulfonylureas, thiazolidinediones, or insulin for any reason Known hypersensitivity or intolerance to metformin hydrochloride 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) Subject has had prior prostatic surgery including TUNA, TURP, TUIP, laser treatment, thermotherapy, balloon dilatation, prosthesis, and ultrasound ablation within 3 months of screening 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 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 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 Serum creatinine > 1.8 X ULN 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 History or current evidence of substance abuse, as defined in DSM-IV, within 12 months of screening 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 No other concurrent metformin hydrochloride, sulfonylureas, thiazolidinediones, or insulin for any reason

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br> | Drug: Metformin<br>* One month run-in of 850mg metformin once daily, followed by 850mg twice daily of metformin for 35 months. Total time is 36 months.<br>* Other names: Metformin hydrochloride;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* One month run-in of placebo tablet once daily, followed by twice daily for 35 months. Total time is 36 months.<br>* Other names: Placebo tablet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to progression | Time to progression - progression is defined as the earliest of the following events: Primary therapy for prostate cancer (e.g. prostatectomy, radiation, hormonal therapy) Pathological progression as defined as one of the following: i. >1/3 of total amount of cores involved ii. At least 50% of any one core involved iii. Gleason pattern 4 or higher | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to primary therapy for prostate cancer | Length of time before the participants move on to more radical treatment options (prostatectomy, radiation and/or hormonal therapy) | 3 years | 
| Time to pathological progression |  | 3 years | 
| Change from baseline in disease-related patient anxiety | Measured by the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) | 3 years | 
| Change from baseline in decisional satisfaction and decisional conflict | Measured by the Decisional Regret scale | 3 years | 
| Change from baseline in prostate cancer diagnosis at repeat biopsy |  | 3 years | 
| Change in Gleason Score at repeat biopsy |  | 3 years | 
| Change in clinical stage of prostate cancer based on digital rectal examination |  | 3 years | 
| Assess the prognostic and predictive value of prostate cancer biomarkers | Using biomarkers in tissue, blood and urine samples | 3 years | 
| 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 |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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localized, prostate, cancer, metformin, active surveillance