The Metformin Active Surveillance Trial (MAST) Study

Prostate Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01864096
• Other study ID #: MAST 01
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 2013
• Est. completion date: August 2024

Study information

• Verified date: January 2024
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 408
• Est. completion date: August 2024
• Est. primary completion date: February 16, 2024
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 79 Years

Eligibility

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

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 5a-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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

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.
• Placebo
One month run-in of placebo tablet once daily, followed by twice daily for 35 months. Total time is 36 months.

Locations

Country	Name	City	State
Canada	Alberta Urology Institute	Edmonton
Canada	CDHA - Victoria Site	Halifax	Nova Scotia
Canada	McMaster Institute of Urology-St .Joseph's Healthcare	Hamilton	Ontario
Canada	Centre for Appled Urologic Research, Kingston General Hospital	Kingston	Ontario
Canada	London Health Sciences Centre-Victoria Hospital	London	Ontario
Canada	Centre L'Hopitalie de l'Universite de Montreal	Montreal	Quebec
Canada	MUHC - Montreal General Hospital	Montreal	Quebec
Canada	Ottawa Hospital Research Institute (The Ottawa Hospital)	Ottawa	Ontario
Canada	Centre de Recherche du CHUS	Sherbrooke	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Canada	Sunnybrook Research Institute	Toronto	Ontario
Canada	Manitoba Cancer Care Centre	Winnipeg	Manitoba

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	Time to pathological progression		3 years
Secondary	Change from baseline in disease-related patient anxiety	Measured by the Memorial Anxiety Scale for Prostate Cancer (MAX-PC)	3 years
Secondary	Change from baseline in decisional satisfaction and decisional conflict	Measured by the Decisional Regret scale	3 years
Secondary	Change from baseline in prostate cancer diagnosis at repeat biopsy		3 years
Secondary	Change in Gleason Score at repeat biopsy		3 years
Secondary	Change in clinical stage of prostate cancer based on digital rectal examination		3 years
Secondary	Assess the prognostic and predictive value of prostate cancer biomarkers	Using biomarkers in tissue, blood and urine samples	3 years
Secondary	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