Prostatic Neoplasm | Prevention of Metabolic Syndrome and Increased Weight Using Metformin Concurrent to Androgen Deprivation Therapy and Radiotherapy for Locally Advanced Adenocarcinoma of the Prostate
Prostatic Neoplasm research study
What is the primary objective of this study?
In current clinical practice, an acceptable standard treatment for locally advanced prostate cancer is radiation therapy in combination with hormone therapy (called Treatment B or Group B in this study). However, despite our best treatments, there is a risk that the prostate cancer may eventually return. As well, the hormonal therapy that is given to treat the prostate cancer is known to cause some harmful effects, with some patients using the hormones gaining weight, developing diabetes, having increased cholesterol levels, having increased blood pressure, and/or heart problems. This study is looking at whether Metformin, a drug that is commonly used to treat diabetes, can prevent patients from developing some of the harmful effects of the hormonal therapy. In treating diabetes, Metformin is known to decrease patients' sugar levels and also prevents patients from gaining weight, decreases their cholesterol levels, decreases the number of heart problems and allows patients to live longer. As a result, the researchers in this study are hopeful that Metformin will also be beneficial for men with prostate cancer on hormonal therapy by preventing them from developing these problems.
Who is eligible to participate?
Inclusion Criteria: 1. Males ≥ 18 years of age 2. Pathologically confirmed, adenocarcinoma of the prostate with either high-tier intermediate or high risk prostate cancer: a. High-tier intermediate risk prostate cancer: i. Gleason score = 7 and PSA 10 - 20 ng/mL b. High risk prostate cancer: i. any T3; or ii. Gleason Score ≥ 8.0; or iii. PSA ≥ 20 ng/mL. 3. Normoglycemic or Impaired Fasting Glucose45 defined as: 1. Fasting Plasma Glucose of ≤ 6.9; or 2. HbA1c of <6.5% 4. Deemed fit to undergo curative intent external beam radiation therapy with concurrent androgen deprivation therapy by their attending radiation oncologist. 5. Accessible for follow-up clinical and laboratory assessments. Exclusion Criteria: 1. Patients with evidence (either by imaging or pathology) of distant metastatic spread of their disease. a. Patients with pelvic lymph nodes (i.e. N1 disease) are NOT considered to have distant metastases and can be included in the trial, if meeting the other study criteria. 2. PSA ≥ 100 ng/mL 3. Patients that meet ≥1 of the Canadian Diabetes Association criteria45 for the diagnosis of diabetes: 1. Fasting Plasma Glucose of ≥ 7.0 mmol/L; or 2. HbA1C ≥ 6.5%; or 3. Plasma Glucose level of ≥ 11.1 mmol/L 2 hours following a 75g oral glucose load, if known, within past 28 days; or 4. Random Plasma Glucose level of ≥ 11.1 mmol/L, if known, within past 28 days 4. Patient who currently take metformin or those who have taken metformin within the past 12 months. 5. History of lactic acidosis or conditions that predispose to lactic acidosis including32: a. Impaired Renal Function (eGFR < 30); or b. Liver disease, including alcoholic liver disease, as demonstrated by any of the following parameters: i. AST >1.8 x the upper limit of normal ii. ALT > 1.8 x the upper limit of normal iii. Alkaline Phosphatase > 2x the upper limit of normal iv. Serum total bilirubin ≥ upper limit of normal c. Alcohol abuse (habitual intake of ≥3 alcoholic beverages per day) sufficient to cause hepatic toxicity d. Severe infection 6. Patients with prior bilateral orchiectomy. 7. Patients with prior prostatectomy 8. Patients who are unable to provide informed consent 9. Prior history of malignancy (with exception of adequately treated non-melanomatous skin cancer or other solid tumors treated curatively with no evidence of disease for ≥ 5 years). 10. Patients on hormonal therapy for more than 3 months prior to registration in the trial.
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:MetforminMetformin 500 mg PO TID x 30-36 months
Drug:PlaceboIdentical placebo TID x 30-36 months
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
MetforminMetformin 500 mg PO TID x 30-36 months
PlaceboIdentical placebo TID x 30-36 months
Start Date: September 2014
Completed Date: September 2018
Phase: Phase 2
Primary Outcome: Mean body weight at 12 months of follow-up
Secondary Outcome: Prevalence and incidence of Metabolic Syndrome
Study sponsors, principal investigator, and references
Principal Investigator: Nawaid Usmani, MD
Lead Sponsor: AHS Cancer Control Alberta