Prostate Cancer
Conditions
Keywords
localized, prostate, cancer, metformin, active surveillance
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.
Interventions
DRUGMetformin
One month run-in of 850mg metformin once daily, followed by 850mg twice daily of metformin for 35 months. Total time is 36 months.
DRUGPlacebo
One month run-in of placebo tablet once daily, followed by twice daily for 35 months. Total time is 36 months.
Sponsors
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 79 Years
Healthy volunteers
No
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Time to pathological progression | 3 years | — |
| Change from baseline in disease-related patient anxiety | 3 years | Measured by the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) |
| Change from baseline in decisional satisfaction and decisional conflict | 3 years | Measured by the Decisional Regret scale |
| Change from baseline in prostate cancer diagnosis at repeat biopsy | 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 in clinical stage of prostate cancer based on digital rectal examination | 3 years | — |
| Assess the prognostic and predictive value of prostate cancer biomarkers | 3 years | 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 | 3 years | — |
| Change in Gleason Score at repeat biopsy | 3 years | — |
Countries
Canada
Outcome results
None listed