The Metformin Active Surveillance Trial (MAST) Study

Phase 3

Active, not recruiting

• Conditions: Prostate Cancer
• Interventions: Drug: Placebo; Drug: Metformin

• Registration Number: NCT01864096
• Lead Sponsor: University Health Network, Toronto

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-05-23
• Study First Submitted QC: 2013-05-23
• Study First Posted: 2013-05-29
• Study Start: 2013-10
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-23
• Last Update Posted: 2024-01-24
• Primary Completion: 2024-02-16
• Study Completion: 2024-08

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: Male
• Target Recruitment: 408

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo tablets, 2teice daily for 36 months
Metformin	Metformin	Metformin 850 mg, twice daily for 36 months

Primary Outcome Measures

Name	Time	Method
Time to progression	3 years	Time to progression - progression is defined as the earliest of the following events: 1. Primary therapy for prostate cancer (e.g. prostatectomy, radiation, hormonal therapy); 2. 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

Secondary Outcome Measures

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

Trial Locations

Locations (12)

Princess Margaret Cancer Centre; 🇨🇦 Toronto, Ontario, Canada

London Health Sciences Centre-Victoria Hospital; 🇨🇦 London, Ontario, Canada

MUHC - Montreal General Hospital; 🇨🇦 Montreal, Quebec, Canada

McMaster Institute of Urology-St .Joseph's Healthcare; 🇨🇦 Hamilton, Ontario, Canada

CDHA - Victoria Site; 🇨🇦 Halifax, Nova Scotia, Canada

Alberta Urology Institute; 🇨🇦 Edmonton, Canada

Ottawa Hospital Research Institute (The Ottawa Hospital); 🇨🇦 Ottawa, Ontario, Canada

Manitoba Cancer Care Centre; 🇨🇦 Winnipeg, Manitoba, Canada

Centre for Appled Urologic Research, Kingston General Hospital; 🇨🇦 Kingston, Ontario, Canada

Sunnybrook Research Institute; 🇨🇦 Toronto, Ontario, Canada

Centre de Recherche du CHUS; 🇨🇦 Sherbrooke, Quebec, Canada

Centre L'Hopitalie de l'Universite de Montreal; 🇨🇦 Montreal, Quebec, Canada