None listed
Conditions
Brief summary
This study will investigate the effects of combining metformin with androgen deprivation therapy (ADT) in men with metastatic prostate cancer. You may be eligible to join this study if you are male, aged 18 years or above and have been diagnosed with metastatic prostate adenocarcinoma, for which you have not received any ADT. Study details Participants in this study are randomly allocated (by chance) to one of two groups. Participants in one group will take 3 x 500mg oral tablets of metformin hydrochloride daily for 30 weeks, whilst participants in the other group will take 3 oral tablets of placebo (inactive treatment) daily for 30 weeks. Participants will be followed-up every 6 weeks for 54 weeks, in order to determine metabolic and tumour responses and tumour progression.
Interventions
This is a two-arm study. Both Arm 1 and Arm 2 will be receiving androgen deprivation therapy (ADT). The ADT used is a combined androgen blockade with luteinizing hormone releasing hormone (LHRH) agonist (45mg EligardTrademark) and AR antagonist (50mg Cosudex/bicalutamide) for the first 4 weeks as per standard of care. After that, EligardTrademark will continue as monotherapy 6 monthly unless clinically indicated for complete androgen blockade. At 12 weeks into ADT, participants will receive 1500
This is a two-arm study. Both Arm 1 and Arm 2 will be receiving androgen deprivation therapy (ADT). The ADT used is a combined androgen blockade with luteinizing hormone releasing hormone (LHRH) agonist (45mg EligardTrademark) and AR antagonist (50mg Cosudex/bicalutamide) for the first 4 weeks as per standard of care. After that, EligardTrademark will continue as monotherapy 6 monthly unless clinically indicated for complete androgen blockade. At 12 weeks into ADT, participants will receive 1500mg metformin (3x500mg daily, with meals) or placebo depending on the treatment arm allocated after randomization. Metformin or Placebo tablets will be dispensed every 12 weeks. Participants will need to return the unused tablets to the research team before or after each dispensing for drug accountability purpose. Moreover, participants will have 6 weekly medical review. Arm 1 Metformin hydrochloride 500mg tablet Dosage: 1500mg daily Duration: 30 weeks Mode of administration: Oral
Sponsors
Queensland University of Technology
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject)
Eligibility
Sex/Gender
Male
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age above 18 years 2. Competent to understand information and provide written informed consent 3. Metastatic prostate adenocarcinoma defined by radiological diagnosis (TNM staging), PSA greater or than equal to 20 in the presence of tissue diagnosis or abnormal prostate examination, PSA recurrence post surgery or radiotherapy 4. No prior chemotherapy for prostate cancer 5. Not on insulin control medications [Insulin, oral hypoglycaemic agents, systemic corticosteroid of any dosage, atypical antipsychotic drugs of any dose] 6. Adequate renal function (Creatinine equal to 177mmol/L, GFR greater than 30 mls/min) 7. Adequate hepatic function (Bilirubin must be equal to 1.5 x upper limit of normal range, ALT and ALP must be equal to 2.5 x upper limit of normal) 8. Life expectancy greater than 6 months
Exclusion criteria
1. Known brain metastasis 2. Malignant disease other than prostate cancer at the time of enrolment, apart from completely treated non-melanomatous skin malignancy 3. Prior chemotherapy for prostate cancer 4. Prior primary radiotherapy within 6 weeks 5. Previously treated with ketoconazole for greater than 7 days 6. Prior systemic treatment with an azole drug within 4 weeks 7. Prior antiandrogen treatment within 6 weeks 8. History of lactic acidosis 9. History of pituitary or adrenal dysfunction 10. Cardiac (heart failure NYHA class II or greater, acute myocardial infarct, unstable angina, arterial-thromboembolic event within past 6 months) or respiratory insufficiency (active pulmonary embolism, severe chronic obstructive pulmondary disease), severe liver failure (cirrhosis with a Child-Pugh level of B or greater), severe infection that is likely to increase the risk of lactic acidosis 11. Medical or psychiatric conditions that compromise the patient's ability to give informed consent 12. History of pituitary or adrenal dysfunction 13. Participants will be discharged from the study if unable to tolerate metformin due to adverse reactions or develop medical conditions such as renal failure or diabetes requiring additional agents other than metformin
Outcome results
None listed