A Phase 3 interventional study of Metformin and Placebo Oral Tablet in Prostate Cancer and Metabolic Syndrome, sponsored by Canadian Urologic Oncology Group. Terminated at 16 sites in Canada. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-29.
Sponsored by Canadian Urologic Oncology Group · Phase 3, Interventional, and Prevention
This is a multi-centre, double-blind, randomized phase III trial comparing metformin to placebo in patients with advanced prostate cancer starting (or have recently started) androgen deprivation therapy (ADT).
The primary objective of this study will determine if there are differences between arms with respect to the proportion of participants who meet the diagnostic criteria for metabolic syndrome after 18 months of study treatment.
The investigators 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.
6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.
This study's enrollment of 166 is above the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.
Browse Prostatic Neoplasms studies →This is the only study on the registry with Canadian Urologic Oncology Group as lead sponsor.
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Participants must fulfill all the following criteria to be eligible for admission to the study:
Eligible for initiating androgen deprivation therapy with either:
Biochemical recurrence of prostate cancer as defined as EITHER:
Exclusion Criteria
Participants who fulfill any of the following criteria are not eligible for admission to the study:
Prior androgen deprivation therapy within 12 months of enrolment (except for participants who have started androgen deprivation therapy within 45 days of commencing study treatment)
Participant that meet ≥ 1 of the Canadian Diabetes Association criteria for the diagnosis of diabetes within 28 days of enrolment:
History of lactic acidosis or conditions that predispose to lactic acidosis:
Liver disease, including alcoholic liver disease, as demonstrated by any of the following parameters:
Metformin 850 mg PO OD X 30 days, then 850mg PO BID for a total of 18 months
Drug: Metformin
Placebo Oral Tablet 1 tablet (850mg) PO OD X 30 days, then 850mg PO BID for a total of 18 months
Drug: Placebo Oral Tablet
Metformin Duration: 18 months 850 mg PO OD x 30 days then 850 mg PO BID for duration
Placebo Oral Tablet Duration 18 months 1 tablet (850 mg) PO OD x 30 days then 1 tablet PO BID for duration
Also known as: Placebo
Proportion of participants who meet the diagnostic criteria for metabolic syndrome after 18 months of study treatment
A diagnosis of metabolic syndrome will be made according to the harmonized definition of the metabolic syndrome as defined in the joint statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and the International Association for the Study of Obesity. A patient will be classified as having metabolic syndrome if he possesses ≥3 of the aforementioned criteria: Increased waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting blood glucose. The prevalence of metabolic syndrome at 18 months post randomization will be calculated and compared between treatment arms using the two-sample t-test.
Time frame: 18 months
Proportion of participants who meet the diagnostic criteria for metabolic syndrome after 9 months of study treatment
A diagnosis of metabolic syndrome will be made according to the harmonized definition of the metabolic syndrome as defined in the joint statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and the International Association for the Study of Obesity. A patient will be classified as having metabolic syndrome if he possesses ≥3 of the aforementioned criteria: Increased waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting blood glucose. The prevalence of metabolic syndrome at 9 months post randomization will be calculated and compared between treatment arms using the two-sample t-test.
Time frame: 9 months
Proportion of participants who meet the diagnostic criteria for metabolic syndrome after 12 months of study treatment
A diagnosis of metabolic syndrome will be made according to the harmonized definition of the metabolic syndrome as defined in the joint statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and the International Association for the Study of Obesity. A patient will be classified as having metabolic syndrome if he possesses ≥3 of the aforementioned criteria: Increased waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting blood glucose. The prevalence of metabolic syndrome at 12 months post randomization will be calculated and compared between treatment arms using the two-sample t-test.
Time frame: 12 months
Proportion of participants who meet the diagnostic criteria for metabolic syndrome after 24 months of study treatment
A diagnosis of metabolic syndrome will be made according to the harmonized definition of the metabolic syndrome as defined in the joint statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and the International Association for the Study of Obesity. A patient will be classified as having metabolic syndrome if he possesses ≥3 of the aforementioned criteria: Increased waist circumference, elevated triglycerides, reduced high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting blood glucose. The prevalence of metabolic syndrome at 24 months post randomization will be calculated and compared between treatment arms using the two-sample t-test.
Time frame: 24 months
Proportion of participants who meet the criteria of reduced high-density lipoprotein cholesterol assessed at 18 months of follow-up.
Reduced High-Density Lipoprotein Cholesterol defined as: \< 1.0 mmol/L; or drug treatment for reduced HDL cholesterol\* \*Patient taking fibrates (Bezafibrate, Ciprofibrate, Clofibrate, Gemfibrozil, or Fenofibrate) or nicotinic acid can be presumed to have high TG and reduced HDL-cholesterol levels; Patients taking high dose omega-3 fatty acids can be presumed to have high TG levels
Time frame: 18 months
Proportion of participants who meet the criteria of elevated triglycerides assessed at 18 months of follow-up.
Elevated Triglycerides defined as: ≥1.7 mmol/L; or drug treatment for elevated triglycerides\* \*Patient taking fibrates (Bezafibrate, Ciprofibrate, Clofibrate, Gemfibrozil, or Fenofibrate) or nicotinic acid can be presumed to have high TG and reduced HDL-cholesterol levels; Patients taking high dose omega-3 fatty acids can be presumed to have high TG levels
Time frame: 18 months
Proportion of participants who meet the criteria of elevated blood pressure assessed at 18 months of follow-up.
Elevated Blood Pressure defined as: Systolic Blood Pressure of ≥ 130 mm of Hg; or Diastolic Blood Pressure of ≥ 85 mm of Hg; or drug treatment for elevated blood pressure Blood pressures will be taken with patients sitting for 5 minutes in a quiet environment prior to measurement and two measurements taken (with a minimum of 5 minutes between each blood pressure measurement), with the mean recorded for this study.
Time frame: 18 months
Proportion of participants who meet the criteria of elevated fasting blood glucose levels assessed at 18 months of follow-up.
Elevated Fasting Blood Glucose defined as: HbA1c ≥ 6.5%; or Fasting plasma glucose ≥ 7.0 mmol/L; or drug treatment for elevated blood glucose
Time frame: 18 months
Proportion of participants who meet the criteria of increased waist circumference assessed at 18 months of follow-up.
Increased Waist Circumference defined as: Males (population and country specific) A) Canadians ≥102cm B) Chinese ≥ 85cm C) Japanese ≥ 85 cm D) Other Asians ≥ 90 cm E) Middle Eastern \& Mediterranean ≥ 94cm F) Sub-Saharan African ≥ 94 cm G) Central \& South American ≥ 90cm H) Europid ≥ 94 cm Measurement of waist circumference will be performed by a dedicated research nurse for this study that is blinded to the patient's treatment allocation.
Time frame: 18 months
Health-related Quality of Life assessed at 18 months of follow-up.
Patients will undergo quality of life measurements by the EORTC QLQ-C30 core questionnaire (63) and prostate-specific module. The instruments are well validated and widely used in the population of interest. The questionnaire items are transformed for 5 functional domains, global QOL, and specific symptom scales/items relevant to the study intervention. The statistical analysis plan will use the standard CCTG QOL approach (Osoba et al., 1998), and will focus on change of mean scores from baseline over time by treatment allocation group. Depending on the amount of missing data, generalized linear equation modeling of mean scores may be required. The analysis will also consider the proportion of patients improved, stable or deteriorated at 18 months compared to baseline using a cut-point minimal clinical difference of 10 points on all scales. A sensitivity analysis will be executed using a cut-point of 7 points.
Time frame: 18 months
Treatment-related toxicity
Treatment related toxicity (NCI CTCAE 4.0) All men will be evaluated for toxicity from the time of their first oral dose of study medication. Toxicities will be graded using the current CTCAE version 4.0. The incidence of toxicities by arm will be summarized by type of adverse effect. A Fisher's Exact Test will be used to compare toxicities between the two arms.
Time frame: 18 months
Serum insulin levels assessed at 18 months of follow-up.
Fasting insulin level Test for significance: Two sample independent t-test.
Time frame: 18 months
Insulin resistance assessed at 18 months of follow-up.
The homoeostasis model assessment insulin resistance (HOMA-IR) (67, 68) and the Quantitative Insulin Sensitivity Check Index (QUICKI) (69), indirect measures of insulin resistance, will be the primary means of classifying insulin resistance status for this study. HOMA-IR = Fasting Insulin (μU/ml) \* Fasting glucose (mmol/L) 22.5 QUICKI = 1/\[log fasting insulin (mU/L) + log fasting glucose (mg/dl)\]
Time frame: 18 months
Time to re-initiation of androgen deprivation therapy (in the subset of patients receiving intermittent therapy)
The median duration of time off-treatment (i.e. ADT) in days will be compared between study arms using the student t-test.
Time frame: 18 months
Duration of time off-treatment in days
The median duration of time off-treatment (i.e. ADT) in days will be compared between study arms (in the subset of patients on intermittent ADT) using the student t-test.
Time frame: 18 months
Testosterone levels assessed at 18 months of follow-up.
Testosterone to be measured as per standard of care (usually every 3 months during initiation of ADT and initial off-ADT period).
Time frame: 18 months
Body mass assessed at 18 months of follow-up.
Measurement weight will be performed by a dedicated research nurse for this study that is blinded to the patient's treatment allocation.
Time frame: 18 months
Abdominal girth assessed at 18 months of follow-up.
Measurement of abdominal girth will be performed by a dedicated research nurse for this study that is blinded to the patient's treatment allocation.
Time frame: 18 months
Mean BMI assessed at 12 months of follow-up.
Measurement of height and weight will be performed by a dedicated research nurse for this study that is blinded to the patient's treatment allocation.
Time frame: 12 months
Mean BMI assessed at 24 months of follow-up.
Measurement of height and weight will be performed by a dedicated research nurse for this study that is blinded to the patient's treatment allocation.
Time frame: 24 months
Mean BMI assessed at 36 months of follow-up.
Measurement of height and weight will be performed by a dedicated research nurse for this study that is blinded to the patient's treatment allocation.
Time frame: 36 months
Exercise behavior and sedentary behavior assessed at 12 months of follow-up.
Exercise/sedentary questionnaire will be administered at 12 months of follow-up. Analyses of covariance (ANCOVA) to explore the effects of the intervention on moderate exercise minutes, vigorous exercise minutes, combined moderate and vigorous exercise minutes, and sedentary behavior hours will be conducted. Chi-square analyses to examine the effects of the intervention on meeting the exercise guidelines will be done.
Time frame: 12 months
Exercise behavior and sedentary behavior assessed at 24 months of follow-up.
Exercise/sedentary questionnaire will be administered at 24 months of follow-up. Analyses of covariance (ANCOVA) to explore the effects of the intervention on moderate exercise minutes, vigorous exercise minutes, combined moderate and vigorous exercise minutes, and sedentary behavior hours will be conducted. Chi-square analyses to examine the effects of the intervention on meeting the exercise guidelines will be done.
Time frame: 24 months
Exercise behavior and sedentary behavior assessed at 36 months of follow-up.
Exercise/sedentary questionnaire will be administered at 36 months of follow-up. Analyses of covariance (ANCOVA) to explore the effects of the intervention on moderate exercise minutes, vigorous exercise minutes, combined moderate and vigorous exercise minutes, and sedentary behavior hours will be conducted. Chi-square analyses to examine the effects of the intervention on meeting the exercise guidelines will be done.
Time frame: 36 months
Cardiovascular mortality
For cardiovascular morality, the survival period will be defined as the date of randomization to the date of death due to cardiovascular disease or the date of censoring. All deaths that occur amongst study participants will be reviewed by the study's data safety and monitoring committee (who will be blinded to the treatment allocation of the patient in question). Deaths will be classified into 3 categories: 1) Prostate Cancer 2) Cardiovascular Disease 3) Other. Cardiovascular deaths will include cases in which cardiovascular disease, coronary artery disease, or stroke are identified as one of the causes of death, not just the underlying cause of death.
Time frame: Through study completion, an average of 3 years
Biochemical progression-free survival
For bPFS, the survival period will be defined as the date of randomization to the date of biochemical progression or the date of censoring. For the purposes of this study, biochemical progression will be defined as a rise in serum PSA above their pre-randomization level (or 10ng/mL for patients who had a baseline PSA \>10ng/mL) or the initiation of cancer treatment (i.e. second course of hormonal therapy, systemic therapy, etc.).
Time frame: 36 months
Castration resistant disease-free survival
For RFS-CR, the survival period will be defined as the date of randomization to the date of confirmed biochemical castration resistance or the date of censoring. For the purposes of this study, castration resistance will be defined as a continuous rise in serum PSA despite castrate levels of serum testosterone (achieved via total androgen blockade).
Time frame: 36 months
Distant metastasis disease-free survival
For RFS-DM, the survival period will be defined as the date of randomization to the date of confirmation of distant metastases or the date of censoring. Any of the following constitute a confirmation of distant metastases: imaging evidence of de novo bone metastases (X-rays, bone scan, CT, MRI, or PET scan), pathological fracture secondary to a bone metastases, imaging evidence of lymph node metastases (CT, MRI or Ultrasound Scans).
Time frame: 36 months
Prostate cancer specific survival
For PCSS, the survival period will be defined as the date of randomization to the date of death due to prostate cancer or the date of censoring. All deaths that occur amongst study participants will be reviewed by the study's data safety and monitoring committee (who will be blinded to the study arm allocation of the patient in question). Any death that is determined to be attributable to a participant's prostate cancer will be deemed a death due to prostate cancer.
Time frame: Through study completion, an average of 3 years
Overall survival
For OS, the survival period will be defined as the date of randomization to the date of death due to any cause or the date of censoring. All deaths that occur amongst study participants will be reviewed by the study's data safety and monitoring committee (who will be blinded to the treatment allocation of the patient in question). Deaths will be classified into 3 categories: 1) Prostate Cancer 2) Cardiovascular Disease 3) Other.
Time frame: Through study completion, an average of 3 years
This study is terminated, as verified in Oct 2024. You cannot join it, but the record below documents what was studied.
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