The Metformin Active Surveillance Trial (MAST) Study (MAST)

• Sponsor: University Health Network, Toronto
• Information provided by (Responsible Party): University Health Network, Toronto

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Metformin; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 408 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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 Start Date: October 2013
• Estimated Primary Completion Date: August 2023
• Estimated Study Completion Date: August 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Metformin	Drug: Metformin; One month run-in of 850mg metformin once daily, followed by 850mg twice daily of metformin for 35 months. Total time is 36 months.; Other Name: Metformin hydrochloride
Placebo Comparator: Placebo	Drug: Placebo; One month run-in of placebo tablet once daily, followed by twice daily for 35 months. Total time is 36 months.; Other Name: Placebo tablet

Outcome Measures

Primary Outcome Measures :

1. Time to progression [ Time Frame: 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. At least 4 cores involved ii. At least 50% of any one core involved iii. Gleason pattern 4 or higher

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 79 Years (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

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, < 3 cores positive 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

Contacts and Locations

Contacts

Contact: Miran Kenk, PhD; 416-946-4501 ext 3431; miran.kenk@uhn.ca

Contact: Heidi Wagner, BSc, PA (ASPC); (416) 946-4501 ext 2354; heidi.wagner@uhn.ca

Locations

Canada, Manitoba

Manitoba Cancer Care Centre; Recruiting

Winnipeg, Manitoba, Canada, R3E 0V9

Principal Investigator: Darrel Drachenberg, MD

Canada, Nova Scotia

CDHA - Victoria Site; Recruiting

Halifax, Nova Scotia, Canada, B2H 1Y6

Principal Investigator: Ricardo Rendon, MD

Canada, Ontario

McMaster Institute of Urology-St .Joseph's Healthcare; Recruiting

Hamilton, Ontario, Canada, L8N 4A6

Principal Investigator: Bobby Shayegan, MD

Centre for Appled Urologic Research, Kingston General Hospital; Recruiting

Kingston, Ontario, Canada, K7L 3J7

Principal Investigator: Michael Leveridge, MD

London Health Sciences Centre-Victoria Hospital; Recruiting

London, Ontario, Canada, N6A 5W9

Principal Investigator: Jonathan Izawa, MD

Ottawa Hospital Research Institute (The Ottawa Hospital); Recruiting

Ottawa, Ontario, Canada, K1H 8L6

Principal Investigator: Rodney Breau, MD

Sunnybrook Research Institute; Recruiting

Toronto, Ontario, Canada, M4N 3M5

Principal Investigator: Laurence Klotz, MD

Princess Margaret Cancer Centre; Recruiting

Toronto, Ontario, Canada, M5G 2M9

Principal Investigator: Neil Fleshner, MD

Principal Investigator: Anthony Joshua, MD

Canada, Quebec

Centre L'Hopitalie de l'Universite de Montreal; Recruiting

Montreal, Quebec, Canada, H2L 4M1

Principal Investigator: Fred Saad, MD

MUHC - Montreal General Hospital; Recruiting

Montreal, Quebec, Canada

Principal Investigator: Simon Tanguay

Centre de Recherche du CHUS; Recruiting

Sherbrooke, Quebec, Canada, J1J 3H5

Contact: Elsie Morneau, BSN 819-346-1110 ext 12827 emorneau.chus@ssss.gouv.qc.ca

Principal Investigator: Patrick Richard, MD

Canada

Alberta Urology Institute; Recruiting

Edmonton, Canada

Contact: Adrian Fairey, FRCSC, MD, MSc.

Sponsors and Collaborators

University Health Network, Toronto

Investigators

• Principal Investigator: Neil Fleshner, MD, MPH, FRCSC; University Health Network: Department of Surgical Oncology (Urology)
• Principal Investigator: Anthony Joshua, MD; University Health Network: Department of Surgical Oncology (Urology)

More Information

• Responsible Party: University Health Network, Toronto
• ClinicalTrials.gov Identifier: NCT01864096 History of Changes
• Other Study ID Numbers: MAST 01
• First Posted: May 29, 2013
• Last Update Posted: April 10, 2019
• Last Verified: April 2019

Keywords provided by University Health Network, Toronto:

localized; prostate; cancer; metformin; active surveillance

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Metformin; Hypoglycemic Agents; Physiological Effects of Drugs