Metformin in Patients Initiating ADT as Prevention and Intervention of Metabolic Syndrome

Official Title

A Randomized Phase 3 Trial of Metformin in Patients Initiating Androgen Deprivation Therapy as Prevention and Intervention of Metabolic Syndrome: The Prime Study

Summary:

This is a multi-centre, double-blind, randomized phase III trial comparing metformin to placebo in patients with advanced prostate cancer starting androgen deprivation therapy.

Trial Description

Primary Outcome:

• Proportion of participants who meet the diagnostic criteria for metabolic syndrome after 18 months of study treatment

Secondary Outcome:

• Proportion of participants who meet the diagnostic criteria for metabolic syndrome after 9 months of study treatment
• Proportion of participants who meet the diagnostic criteria for metabolic syndrome after 12 months of study treatment
• Proportion of participants who meet the diagnostic criteria for metabolic syndrome after 24 months of study treatment
• Proportion of participants who meet the criteria of reduced high-density lipoprotein cholesterol assessed at 18 months of follow-up.
• Proportion of participants who meet the criteria of elevated triglycerides assessed at 18 months of follow-up.
• Proportion of participants who meet the criteria of elevated blood pressure assessed at 18 months of follow-up.
• Proportion of participants who meet the criteria of elevated fasting blood glucose levels assessed at 18 months of follow-up.
• Proportion of participants who meet the criteria of increased waist circumference assessed at 18 months of follow-up.
• Health-related Quality of Life assessed at 18 months of follow-up.
• Treatment-related toxicity

The primary objective of this study is to compare treatment arms with respect to the proportion of participants who develop metabolic syndrome. We will also compare arms with regards to severity of individual metabolic syndrome components following 18 months of study treatment. Other objectives are outlined below, and will include quality of life assessments, metabolic and anthropomorphic measurements at additional time points and correlative laboratory studies. It is estimated that one in seven Canadian men will be diagnosed with prostate cancer in their lifetime. In 2015, approximately 23,600 Canadian men were estimated to be diagnosed with prostate cancer and 4,000 died of this disease. Androgen deprivation therapy (ADT) is a standard first-line treatment for men with incurable prostate cancer and has long been known to improve overall survival. Although the effectiveness of ADT is well established in participants with advanced prostate cancer, it is associated with important adverse effects as outlined below. The development of metabolic syndrome in particular is clinically important as it is associated with worsened quality of life and increased all-cause morbidity and mortality. As ADT is now employed, alone or in combination with other therapies, in virtually all men with advanced prostate cancer for increasingly long periods of time (median survival of men presenting with newly diagnosed metastatic disease from recent clinical trials is at least 3 years, during which they are typically on continuous hormonal therapy), the burden of ADT toxicity among men with prostate cancer is significant and increasing. The investigators hypothesize that the addition of metformin to a program of ADT will reduce the proportion of participants with metabolic syndrome at 18 months after initiation of ADT and will reduce the severity of individual components of metabolic syndrome in men with advanced prostate cancer. To test this hypothesis, this is a randomized, double-blinded, placebo-controlled phase 3 clinical trial of metformin in patients undergoing ADT treatment.

View this trial on ClinicalTrials.gov