Prostate Cancer
Conditions
Keywords
metformin, atorvastatin, prostate-specific antigen, biochemical recurrence
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).
Interventions
DRUGMetformin
One month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression.
DRUGAtorvastatin
Atorvastatin 20 mg once daily until progression.
DRUGPlacebo (corresponding to metformin)
One month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression.
DRUGPlacebo (corresponding to atorvastatin)
One placebo tablet (corresponding to atorvastatin) once daily until progression.
Sponsors
University Health Network, Toronto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
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 * Abnormal organ and marrow function
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| 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. | — |
| 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. | Relationship between body mass index and response to anti-metabolic and anti-cholesterol therapy |
| 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. | Relationship between circulating glycated hemoglobin levels and response to anti-metabolic and anti-cholesterol therapy |
| 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. | — |
| 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. | Relationship between adipokine levels and response to anti-metabolic and anti-cholesterol therapy |
| 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. | Relationship between LDL/HDL cholesterol levels and response to anti-metabolic and anti-cholesterol therapy |
| 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. | Relationship between triglyceride levels and response to anti-metabolic and anti-cholesterol therapy |
| 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. | Assessment of incidence of adverse events from the administration of metformin and atorvastatin to men with prostate cancer. |
| 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. | Relationship between C-peptide levels and response to anti-metabolic and anti-cholesterol therapy |
Countries
Canada
Outcome results
None listed