Prostate Cancer Active Surveillance Metformin Trial

Study Overview
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Brief Summary
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To determine whether the use of metformin in patients with low-risk prostate cancer can delay progression to clinically significant prostate cancer.

Official Title
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A Randomized Double Blind Placebo Controlled Single Institution Phase 2 Study of Metformin in Patients Undergoing Active Surveillance for Prostate Cancer.

Conditions
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Prostate Cancer

Intervention / Treatment
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* Drug: Metformin
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>850mg BID | Drug: Metformin<br> <br> |
| Placebo Comparator: Placebo<br> | Drug: placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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