Prevention of Metabolic Syndrome and Increased Weight Using Metformin Concurrent to Androgen Deprivation Therapy and Radiotherapy for Locally Advanced Adenocarcinoma of the Prostate

NCT01996696 | Terminated Phase 2 DMC

• 1 other identifier: CCI-Usmani-01
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Prostatic Neoplasm

Keywords

metformin; metabolic syndrome; weight gain

Outcome Measures

Primary Outcomes (1)

• Mean body weight at 12 months of follow-up

  12 months of follow-up

Secondary Outcomes (1)

• Prevalence and incidence of Metabolic Syndrome

  At 6, 12, 24 and 36 months follow-up

Study Arms (2)

Metformin

EXPERIMENTAL

Metformin 500 mg PO TID x 30-36 months

Drug: Metformin

Placebo

PLACEBO COMPARATOR

Identical placebo TID x 30-36 months

Drug: Placebo

Interventions

Metformin DRUG

Metformin 500 mg PO TID x 30-36 months

Also known as: Fortamet, Glucophage, Glucophage XR, Glumetza, Riomet

Metformin

Placebo DRUG

Identical placebo TID x 30-36 months

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males ≥ 18 years of age
• 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.
• Normoglycemic or Impaired Fasting Glucose45 defined as:
• Fasting Plasma Glucose of ≤ 6.9; or
• HbA1c of \<6.5%
• Deemed fit to undergo curative intent external beam radiation therapy with concurrent androgen deprivation therapy by their attending radiation oncologist.
• Accessible for follow-up clinical and laboratory assessments.

You may not qualify if:

• 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.
• Patients that meet ≥1 of the Canadian Diabetes Association criteria45 for the diagnosis of diabetes:
• Fasting Plasma Glucose of ≥ 7.0 mmol/L; or
• HbA1C ≥ 6.5%; or
• Plasma Glucose level of ≥ 11.1 mmol/L 2 hours following a 75g oral glucose load, if known, within past 28 days; or
• Random Plasma Glucose level of ≥ 11.1 mmol/L, if known, within past 28 days
• Patient who currently take metformin or those who have taken metformin within the past 12 months.
• 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
• Patients with prior bilateral orchiectomy.
• Patients with prior prostatectomy
• Patients who are unable to provide informed consent
• 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).
• Patients on hormonal therapy for more than 3 months prior to registration in the trial.

Sponsors & Collaborators

• AHS Cancer Control Alberta: lead

Study Sites (3)

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Prairie Mountain Health - Western Manitoba Cancer Centre

Brandon, Manitoba, R7A2B3, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms; Metabolic Syndrome; Weight Gain

Interventions

Metformin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Nawaid Usmani, MD

  Cross Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 22, 2013
• First Posted: November 27, 2013
• Study Start: September 1, 2014
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2020
• Last Updated: January 30, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)