Prostate Cancer Active Surveillance Metformin Trial

Tracking Information
First Submitted Date ICMJE	November 20, 2012
First Posted Date ICMJE	November 27, 2012
Last Update Posted Date	May 24, 2013
Study Start Date ICMJE	January 2013
Estimated Primary Completion Date	October 2014 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 26, 2012)	Primary Clinical Outcome - Inhibition of Prostate Cancer [ Time Frame: 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 [ Time Frame: 18 months ]To assess the effect of metformin on the cell cycle proliferation indices (ki67 index).
Original Primary Outcome Measures ICMJE	Same as current
Change History	Complete list of historical versions of study NCT01733836 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 26, 2012)	Secondary Endpoint - Cell Cycle Proliferation (CCP) Score [ Time Frame: 18 months ]To assess the effect of metformin on the cell cycle proliferation indices (CCP score); Secondary Endpoint - Mechanism of Action [ Time Frame: 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 [ Time Frame: 18 months ]To assess the impact of metformin on Quality of Life (QoL) indices.; Secondary Endpoint - Prognostic Panel [ Time Frame: 18 months ]To determine the utility of a prognostic panel of 31 cell cycle progression genes recently validated in prostate cancer.
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Prostate Cancer Active Surveillance Metformin Trial
Official Title ICMJE	A Randomized Double Blind Placebo Controlled Single Institution Phase 2 Study of Metformin in Patients Undergoing Active Surveillance for Prostate Cancer.
Brief Summary	To determine whether the use of metformin in patients with low-risk prostate cancer can delay progression to clinically significant prostate cancer.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition ICMJE	Prostate Cancer
Intervention ICMJE	Drug: Metformin; Drug: placebo
Study Arms	Experimental: Metformin 850mg BID Intervention: Drug: Metformin; Placebo Comparator: Placebo Intervention: Drug: placebo
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Withdrawn
Actual Enrollment ICMJE; (submitted: May 23, 2013)	0
Original Estimated Enrollment ICMJE; (submitted: November 26, 2012)	50
Estimated Study Completion Date	October 2014
Estimated Primary Completion Date	October 2014 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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.
Sex/Gender	Sexes Eligible for Study: Male
Ages	18 Years to 80 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Canada
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01733836
Other Study ID Numbers ICMJE	MAS_001
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	University Health Network, Toronto
Study Sponsor ICMJE	University Health Network, Toronto
Collaborators ICMJE	Not Provided
Investigators ICMJE	Not Provided
PRS Account	University Health Network, Toronto
Verification Date	May 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP