Prostate Cancer Active Surveillance Metformin Trial

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01733836
• Other study ID #: MAS_001
• Status: Withdrawn
• Phase: Phase 2
• First received: November 20, 2012
• Last updated: May 23, 2013
• Start date: January 2013
• Est. completion date: October 2014

Study information

• Verified date: May 2013
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 80 Years

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 a-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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Metformin

• placebo

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario

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	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	Yes
Primary	Primary Scientific Endpoint - ki67 index	To assess the effect of metformin on the cell cycle proliferation indices (ki67 index).	18 months	No
Secondary	Secondary Endpoint - Cell Cycle Proliferation (CCP) Score	To assess the effect of metformin on the cell cycle proliferation indices (CCP score)	18 months	No
Secondary	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	No
Secondary	Secondary endpoint - Quality of Life	To assess the impact of metformin on Quality of Life (QoL) indices.	18 months	No
Secondary	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	No