Prostate Cancer Active Surveillance Metformin Trial

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

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

Study Overview

• Status: Withdrawn
• Conditions: Prostate Cancer
• Intervention / Treatment: Drug: placebo; Drug: Metformin

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo
Experimental: Metformin; 850mg BID	Drug: Metformin

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Health Network, Toronto

Publications and helpful links

General Publications

• Roy S, Malone S, Grimes S, Morgan SC. Impact of Concomitant Medications on Biochemical Outcome in Localised Prostate Cancer Treated with Radiotherapy and Androgen Deprivation Therapy. Clin Oncol (R Coll Radiol). 2021 Mar;33(3):181-190. doi: 10.1016/j.clon.2020.09.005. Epub 2020 Sep 29.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): October 1, 2014
• Study Completion (Anticipated): October 1, 2014

Study Registration Dates

• First Submitted: November 20, 2012
• First Submitted That Met QC Criteria: November 26, 2012
• First Posted (Estimate): November 27, 2012

Study Record Updates

• Last Update Posted (Estimate): May 24, 2013
• Last Update Submitted That Met QC Criteria: May 23, 2013
• Last Verified: May 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Prostatic Neoplasms; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: MAS_001