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

• Status: Recruiting
• Trial end date: 2023-06-01
• Target enrollment: 0
• Participant gender: Male

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: British Columbia Cancer Agency; Canadian Urologic Oncology Group
• Collaborators: British Columbia Cancer Agency; Canadian Urologic Oncology Group; Prostate Cancer Canada
• Treatments: Androgens; Metformin

Criteria

Inclusion Criteria:

• Pathologically confirmed adenocarcinoma of the prostate.

• Eligible for initiating androgen deprivation therapy with either:

• (Neo-)Adjuvant therapy for localized prostate cancer that is planned continuously for at least 9 months; or.

• Metastatic disease; or

• Biochemical recurrence of prostate cancer:

• Rising PSA after prior curative intent local therapy (i.e. prostatectomy with or without adjuvant/ salvage radiotherapy) Since an absolute consensus for this value has not been established, if a rising PSA has been documented by at least two PSA values at least 2 weeks apart, the criteria for biochemical recurrence are deemed to have been met; or

• PSA ≥ 2 ng/mL above their nadir if previously treated with definitive radiotherapy.

• Serum testosterone > 5 nmol/L, except for participants who have already started androgen deprivation therapy (within no more than 45 days)

• The choice of therapy is at the investigators discretion but must include at minimum the use of LHRH agonist/antagonist therapy. The addition of other hormonal agents (e.g. non-steroidal antiandrogens, abiraterone, enzalutamide, apalutamide) is allowed.

• The androgen deprivation therapy undertaken can be intermittent or continuous, but the treatment intent must be declared prior to randomization.

• Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French. The baseline assessment must be completed within required timelines, prior to registration/randomization. Inability (lack of comprehension in English or French, or other equivalent reason such as cognitive issues or lack of competency) to complete the questionnaires will not make the patient ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the patient ineligible.

• Participant consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each participant must sign a consent form prior to enrolment in the trial to document their willingness to participate.

• Participants must be accessible for treatment and follow up. Patients registered on this trial must be treated and followed at the participating centre. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events, and follow-up.

• Protocol treatment is to begin within 7 working days of patient randomization.

Exclusion Criteria:

• Prior androgen deprivation therapy within 12 months of enrolment (except for participants who have started androgen deprivation therapy within 45 days).

• Prior androgen deprivation therapy associated with definitive treatment is permitted, if it has been completed at least 12 months prior to enrolment (i.e. last injection or tablet taken 12 months prior to enrolment).

• Participants that meet ≥ 1 of the Canadian Diabetes Association criteria for the diagnosis of diabetes within 28 days of enrolment:

• Fasting plasma glucose of ≥ 7 mmol/L; or

• HbA1C ≥ 6.5%.

• Participants currently taking metformin or who have taken metformin within 28 days or enrolment.

• History of lactic acidosis or conditions that predispose to lactic acidosis:

• Impaired Renal Function (eGFR < 45 mL/minute/1.73 m2); or

• Liver disease, including alcoholic liver disease, as demonstrated by any of the following parameters:

• AST >1.8 x the upper limit of normal

• ALT > 1.8 x the upper limit of normal

• Alkaline Phosphatase > 2x the upper limit of normal

• Serum total bilirubin > 1.5 x the upper limit of normal (except for subjects with Gilbert's Disease who are eligible despite elevated serum bilirubin levels).

• Alcohol abuse (habitual intake of ≥3 alcoholic beverages per day) sufficient to cause hepatic toxicity; or

• Severe infection.

• Congestive heart failure (defined as New York Heart Association Class III or IV functional status).

• Participants with a history of other invasive malignancies, except adequately treated non-melanoma skin cancer or other solid tumours curatively treated with no evidence of disease for ≥ 5 years.