The Metformin Active Surveillance Trial (MAST) Study | RxWiki

The Metformin Active Surveillance Trial (MAST) Study

Overview[ - collapse ][ - ]

Purpose	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	Prostate Cancer
Intervention	Drug: Metformin Drug: Placebo
Phase	Phase 3
Sponsor	University Health Network, Toronto
Responsible Party	University Health Network, Toronto
ClinicalTrials.gov Identifier	NCT01864096
First Received	May 23, 2013
Last Updated	March 17, 2014
Last verified	March 2014

Tracking Information[ + expand ][ + ]

First Received Date	May 23, 2013
Last Updated Date	March 17, 2014
Start Date	October 2013
Estimated Primary Completion Date	August 2018
Current Primary Outcome Measures	Time to progression [Time Frame: 3 years] [Designated as safety issue: No]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. At least 4 cores involved ii. At least 50% of any one core involved iii. Gleason pattern 4 or higher
Current Secondary Outcome Measures	Time to primary therapy for prostate cancer [Time Frame: 3 years] [Designated as safety issue: No]Length of time before the participants move on to more radical treatment options (prostatectomy, radiation and/or hormonal therapy) Time to pathological progression [Time Frame: 3 years] [Designated as safety issue: No] Change from baseline in disease-related patient anxiety [Time Frame: 3 years] [Designated as safety issue: No]Measured by the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) Change from baseline in decisional satisfaction and decisional conflict [Time Frame: 3 years] [Designated as safety issue: No]Measured by the Decisional Regret scale Change from baseline in prostate cancer diagnosis at repeat biopsy [Time Frame: 3 years] [Designated as safety issue: No] Change in Gleason Score at repeat biopsy [Time Frame: 3 years] [Designated as safety issue: No] Change in clinical stage of prostate cancer based on digital rectal examination [Time Frame: 3 years] [Designated as safety issue: No] Assess the prognostic and predictive value of prostate cancer biomarkers [Time Frame: 3 years] [Designated as safety issue: No]Using biomarkers in tissue, blood and urine samples 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] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief Title	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
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 Provided
Study Type	Interventional
Study Phase	Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
Condition	Prostate Cancer
Intervention	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 Names: Metformin hydrochlorideDrug: Placebo One month run-in of placebo tablet once daily, followed by twice daily for 35 months. Total time is 36 months. Other Names: Placebo tablet
Study Arm (s)	Experimental: Metformin Placebo Comparator: Placebo

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	408
Estimated Completion Date	August 2018
Estimated Primary Completion Date	August 2018
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, < 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
Gender	Male
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Ranjena Maloni, BSc 416-946-4501 ranjena.maloni@uhn.ca
Location Countries	Canada

Administrative Information[ + expand ][ + ]

NCT Number	NCT01864096
Other Study ID Numbers	MAST 01
Has Data Monitoring Committee	Yes
Information Provided By	University Health Network, Toronto
Study Sponsor	University Health Network, Toronto
Collaborators	Not Provided
Investigators	Principal Investigator: Neil Fleshner, MD University Health Network: Department of Surgical Oncology (Urology)Principal Investigator: Anthony Joshua, MD University Health Network: Department of Surgical Oncology (Urology)
Verification Date	March 2014

Locations[ + expand ][ + ]

Manitoba Cancer Care Centre	Winnipeg, Manitoba, Canada, R3E 0V9 Principal Investigator: Darrel Drachenberg, MD Recruiting
CDHA - Victoria Site	Halifax, Nova Scotia, Canada, B2H 1Y6 Principal Investigator: Ricardo Rendon, MD Recruiting
McMaster Institute of Urology-St .Joseph's Healthcare	Hamilton, Ontario, Canada, L8N 4A6 Principal Investigator: Bobby Shayegan, MD Recruiting
Centre for Appled Urologic Research, Kingston General Hospital	Kingston, Ontario, Canada, K7L 3J7 Principal Investigator: Michael Leveridge, MD Recruiting
London Health Sciences Centre-Victoria Hospital	London, Ontario, Canada, N6A 5W9 Principal Investigator: Jonathan Izawa, MD Recruiting
Princess Margaret Cancer Centre	Toronto, Ontario, Canada, M5G 2M9 Principal Investigator: Neil Fleshner, MD Recruiting
Centre L'Hopitalie de l'Universite de Montreal	Montreal, Quebec, Canada, H2L 4M1 Principal Investigator: Fred Saad, MD Recruiting
MUHC - Montreal General Hospital	Montreal, Quebec, Canada Principal Investigator: Simon Tanguay Recruiting
Centre de Recherche Clinique et Evaluative en Oncologie (CRCEO)	Quebec, Canada, G1R 3S1 Principal Investigator: Vincent Fradet, MD Recruiting