A Randomized, Double Blind, Trial of Metformin and Atorvastatin in Delaying Androgen Deprivation Therapy Among Men With Rising PSA Following Radical Prostatectomy or Radiotherapy: The LIGAND (LIpitor and biGuanide to Androgen Delay) Trial
Overview
- Phase
- Phase 2
- Intervention
- Metformin
- Conditions
- Prostate Cancer
- Sponsor
- University Health Network, Toronto
- Locations
- 1
- Primary Endpoint
- Time to disease progression (defined as PSA rise to 10 ng/mL or greater, development of clinically overt metastases) or patient/physician desire for androgen deprivation therapy.
- Status
- Withdrawn
- Last Updated
- 5 years ago
Overview
Brief Summary
This study is a randomized trial examining the administration of a combination of biguanide metformin and atorvastatin ("Lipitor") to men who are experiencing rising prostate-specific antigen (PSA) levels, despite having undergone radical therapy (surgery and/or radiation).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Willing and able to provide informed consent
- •Histologically confirmed adenocarcinoma of the prostate
- •History of radical therapy (i.e., radical prostatectomy, radiotherapy, brachytherapy or prostatectomy with salvage radiotherapy)
- •Serum testosterone levels 8.0 nmol/L (230 ng/dL) or greater
- •Not currently undergoing treatment for hyperlipidemia or diabetes mellitus
- •LDL-cholesterol levels 5 mmol/L or lower
- •HgA1c 6.5% or lower
- •PSA levels between 2 and 5 ng/mL
Exclusion Criteria
- •Subjects that have been treated for prostate cancer with any of the following:
- •i. Cytotoxic chemotherapy; ii. Hormonal therapy within past 3 years; iii. Oral glucocorticoids; iv. Gonadotropin-releasing hormone (GnRH) analogues (e.g., leuprolide, goserelin, degarelix)
- •Past treatment with the 5-α reductase inhibitors finasteride and dutasteride within past 5 years
- •Past treatment with drugs with antiandrogenic properties (e.g., flutamide, bicalutamide, ketoconazole, progestational agents) within 6 months prior to screening
- •Use of metformin or statins within past 2 years
- •Planned or concurrent use of metformin, sulfonylureas, thiazolidinediones or insulin for any reason
- •Known hypersensitivity or intolerance to metformin or atorvastatin
- •Any clinically significant laboratory abnormalities (e.g., severe renal or hepatic impairment) which in the judgment of the investigator would affect the patient's health or the outcome of the trial
- •Any condition associated with increased risk of metformin-associated lactic acidosis (e.g., congestive heart failure defined as New York Heart Association (NYHA) class III or IV, history of any type of acidosis, habitual intake of 4 or more alcoholic beverages per day)
- •Abnormal liver function test
Arms & Interventions
Metformin and Atorvastatin
Atorvastatin 20 mg once daily until progression with one month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression.
Intervention: Metformin
Metformin and Atorvastatin
Atorvastatin 20 mg once daily until progression with one month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression.
Intervention: Atorvastatin
Placebo
One placebo tablet (corresponding to atorvastatin) once daily until progression, with one month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression.
Intervention: Placebo (corresponding to metformin)
Placebo
One placebo tablet (corresponding to atorvastatin) once daily until progression, with one month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression.
Intervention: Placebo (corresponding to atorvastatin)
Outcomes
Primary Outcomes
Time to disease progression (defined as PSA rise to 10 ng/mL or greater, development of clinically overt metastases) or patient/physician desire for androgen deprivation therapy.
Time Frame: From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.
Secondary Outcomes
- Time to disease progression(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Body mass index(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Time to androgen deprivation therapy(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Time to PSA progression(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Circulating glycated hemoglobin levels(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- C-peptide levels(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Adipokine levels(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- LDL/HDL cholesterol levels(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Triglyceride levels(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)
- Incidence of adverse events during administration of metformin and atorvastatin to men with prostate cancer.(From date of randomization until the date of progression or patient/physician desire for androgen deprivation therapy, whichever comes first, assessed up to 36 months.)