The Metformin Active Surveillance Trial (MAST) Study (MAST)
Primary Purpose
Prostate Cancer
Status
Recruiting
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
Metformin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring localized, prostate, cancer, metformin, active surveillance
Eligibility Criteria
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
Sites / Locations
- Manitoba Cancer Care CentreRecruiting
- CDHA - Victoria SiteRecruiting
- McMaster Institute of Urology-St .Joseph's HealthcareRecruiting
- Centre for Appled Urologic Research, Kingston General HospitalRecruiting
- London Health Sciences Centre-Victoria HospitalRecruiting
- Ottawa Hospital Research Institute (The Ottawa Hospital)Recruiting
- Sunnybrook Research InstituteRecruiting
- Princess Margaret Cancer CentreRecruiting
- Centre L'Hopitalie de l'Universite de MontrealRecruiting
- MUHC - Montreal General HospitalRecruiting
- Centre de Recherche du CHUSRecruiting
- Alberta Urology InstituteRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Metformin
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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)
Time to pathological progression
Change from baseline in disease-related patient anxiety
Measured by the Memorial Anxiety Scale for Prostate Cancer (MAX-PC)
Change from baseline in decisional satisfaction and decisional conflict
Measured by the Decisional Regret scale
Change from baseline in prostate cancer diagnosis at repeat biopsy
Change in Gleason Score at repeat biopsy
Change in clinical stage of prostate cancer based on digital rectal examination
Assess the prognostic and predictive value of prostate cancer biomarkers
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
Full Information
NCT ID
NCT01864096
First Posted
May 23, 2013
Last Updated
April 16, 2021
Sponsor
University Health Network, Toronto
1. Study Identification
Unique Protocol Identification Number
NCT01864096
Brief Title
The Metformin Active Surveillance Trial (MAST) Study
Acronym
MAST
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
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Recruiting
Study Start Date
October 2013 (undefined)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
August 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
4. Oversight
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
localized, prostate, cancer, metformin, active surveillance
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
408 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Metformin
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
Metformin hydrochloride
Intervention Description
One month run-in of 850mg metformin once daily, followed by 850mg twice daily of metformin for 35 months. Total time is 36 months.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Placebo tablet
Intervention Description
One month run-in of placebo tablet once daily, followed by twice daily for 35 months. Total time is 36 months.
Primary Outcome Measure Information:
Title
Time to progression
Description
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
Time Frame
3 years
Secondary Outcome Measure Information:
Title
Time to primary therapy for prostate cancer
Description
Length of time before the participants move on to more radical treatment options (prostatectomy, radiation and/or hormonal therapy)
Time Frame
3 years
Title
Time to pathological progression
Time Frame
3 years
Title
Change from baseline in disease-related patient anxiety
Description
Measured by the Memorial Anxiety Scale for Prostate Cancer (MAX-PC)
Time Frame
3 years
Title
Change from baseline in decisional satisfaction and decisional conflict
Description
Measured by the Decisional Regret scale
Time Frame
3 years
Title
Change from baseline in prostate cancer diagnosis at repeat biopsy
Time Frame
3 years
Title
Change in Gleason Score at repeat biopsy
Time Frame
3 years
Title
Change in clinical stage of prostate cancer based on digital rectal examination
Time Frame
3 years
Title
Assess the prognostic and predictive value of prostate cancer biomarkers
Description
Using biomarkers in tissue, blood and urine samples
Time Frame
3 years
Title
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
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Miran Kenk, PhD
Phone
416-946-4501
Ext
3431
Email
miran.kenk@uhn.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Heidi Wagner, BSc, PA (ASPC)
Phone
(416) 946-4501
Ext
2354
Email
heidi.wagner@uhn.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Neil Fleshner, MD, MPH, FRCSC
Organizational Affiliation
University Health Network: Department of Surgical Oncology (Urology)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anthony Joshua, MD
Organizational Affiliation
University Health Network: Department of Surgical Oncology (Urology)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Manitoba Cancer Care Centre
City
Winnipeg
State/Province
Manitoba
ZIP/Postal Code
R3E 0V9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Darrel Drachenberg, MD
Facility Name
CDHA - Victoria Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B2H 1Y6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ricardo Rendon, MD
Facility Name
McMaster Institute of Urology-St .Joseph's Healthcare
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8N 4A6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bobby Shayegan, MD
Facility Name
Centre for Appled Urologic Research, Kingston General Hospital
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 3J7
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Leveridge, MD
Facility Name
London Health Sciences Centre-Victoria Hospital
City
London
State/Province
Ontario
ZIP/Postal Code
N6A 5W9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jonathan Izawa, MD
Facility Name
Ottawa Hospital Research Institute (The Ottawa Hospital)
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rodney Breau, MD
Facility Name
Sunnybrook Research Institute
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laurence Klotz, MD
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neil Fleshner, MD
First Name & Middle Initial & Last Name & Degree
Anthony Joshua, MD
Facility Name
Centre L'Hopitalie de l'Universite de Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2L 4M1
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fred Saad, MD
Facility Name
MUHC - Montreal General Hospital
City
Montreal
State/Province
Quebec
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simon Tanguay
Facility Name
Centre de Recherche du CHUS
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1J 3H5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elsie Morneau, BSN
Phone
819-346-1110
Ext
12827
Email
emorneau.chus@ssss.gouv.qc.ca
First Name & Middle Initial & Last Name & Degree
Patrick Richard, MD
Facility Name
Alberta Urology Institute
City
Edmonton
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adrian Fairey, FRCSC, MD, MSc.
12. IPD Sharing Statement
Learn more about this trial
The Metformin Active Surveillance Trial (MAST) Study
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