Prostate Cancer Active Surveillance Metformin Trial

Recruitment & Eligibility

Inclusion Criteria

Willing and able to provide informed consent
Men >= 18 years of age, and less than 80
Men with biopsy proven, low-risk, localized prostate cancer (as defined below)
Men choosing expectant management as primary treatment for prostate cancer
Diagnostic biopsy performed within 4 months of screening visit
Gleason score ≤ 6 in 3 cores or less with no Gleason pattern 4, less than 50% of any core involved in cancer
Clinical stage T1c-T2a (Initial diagnosis of T1a/T1b obtained during a TURP is not allowed)
Serum PSA ≤10 ng/mL
Life expectancy greater than 5 years
Normal kidney and hepatic function as defined by the following criteria:
- Total bilirubin less than 1.5 X institutional upper limit of normal (ULN)
- AST (SGOT)/ALT(SGPT) less than 1.5 X institutional ULN
- Alkaline phosphatase less than 2 X institutional ULN
- Creatinine less than 1.4 X institutional ULN
Able to swallow and retain oral medication
No exposure to metformin within 12 months of randomization
No known hypersensitivity or intolerance to metformin hydrochloride
No condition associated with increased risk of metformin hydrochloride-associated lactic acidosis (e.g., congestive heart failure defined as NYHA class III or IV function status, history of acidosis of any type, or habitual intake of ≥ 3 alcoholic beverages per day, or age greater than 80)
English fluency allowing for patient reported outcomes completion

Exclusion Criteria

Any previous prostate cancer treatment (radiotherapy, chemotherapy, hormonal therapy, oral glucocorticoids, GnRH analogues)
Diabetes including type 1 diabetes. Patients with known type 2 diabetes are eligible provided they have not been on metformin during the previous 12 months and are not on any other pharmacological agents.
Concurrent or previous use of anabolic steroids or drugs with anti androgenic properties including 5-ARIs (dutasteride and finasteride)
Prostate volume greater than 80 cc. (as per TRUS biopsy report)
Prostatic surgery or procedure within 3 months of screening visit
Severe BPH symptoms (IPSS ≥25, or ≥20 if already on α-blocker therapy)
Other malignancies, with the exception of adequately treated nonmelanoma skin cancer, NMIBC or other solid tumors curatively treated with no evidence of disease for ≥ 5 years
Planned or concurrent participation in other interventional randomized trials including exercise
The presence of any other coexistent medical condition that in the opinion of the investigator would have the potential to significantly limit adherence to medication, or ability to absorb the medication including but not limited to psychiatric conditions, malabsorption syndromes or severe ischemic heart disease
Known hypersensitivity or intolerance to metformin
Concurrent or planned participation in randomized trials of weight loss or exercise interventions or trials targeting insulin, IGF-1 or their receptors, or PI3K inhibitors.

Study & Design

Arm && Interventions

Group	Intervention	Description
Metformin	Metformin	850mg BID
Placebo	placebo	-

Primary Outcome Measures

Name	Time	Method
Primary Clinical Outcome - Inhibition of Prostate Cancer	18 months	To assess the role of metformin on the inhibition of low-risk localized prostate cancer progression in men undergoing active surveillance for prostate cancer.
Primary Scientific Endpoint - ki67 index	18 months	To assess the effect of metformin on the cell cycle proliferation indices (ki67 index).

Secondary Outcome Measures

Name	Time	Method
Secondary Endpoint - Cell Cycle Proliferation (CCP) Score	18 months	To assess the effect of metformin on the cell cycle proliferation indices (CCP score)
Secondary Endpoint - Mechanism of Action	18 months	To assess the effect of metformin on systemic and local signalling axes and morphometric measurements relevant to its mechanism of action.
Secondary endpoint - Quality of Life	18 months	To assess the impact of metformin on Quality of Life (QoL) indices.
Secondary Endpoint - Prognostic Panel	18 months	To determine the utility of a prognostic panel of 31 cell cycle progression genes recently validated in prostate cancer.

Recruitment & Eligibility