Clinical trial NCT02497638: LIpitor and biGuanide to Androgen Delay Trial
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Prostate Cancer
Keywords: metformin
atorvastatin
prostate-specific antigen
biochemical recurrence
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2015-07-14
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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
* Abnormal organ and marrow function

Primary outcomes:
measure: 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.
timeFrame: 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:
measure: Time to androgen deprivation therapy
timeFrame: 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.
measure: Time to PSA progression
timeFrame: 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.
measure: Time to disease progression
timeFrame: 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.
measure: Body mass index
timeFrame: 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.
measure: Circulating glycated hemoglobin levels
timeFrame: 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.
measure: C-peptide levels
timeFrame: 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.
measure: Adipokine levels
timeFrame: 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.
measure: LDL/HDL cholesterol levels
timeFrame: 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.
measure: Triglyceride levels
timeFrame: 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.
measure: Incidence of adverse events during administration of metformin and atorvastatin to men with prostate cancer.
timeFrame: 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.
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Robert Hamilton, MD, MPH, FRCSC
role: PRINCIPAL_INVESTIGATOR
affiliation: University Health Network, Toronto
name: Neil Fleshner, MD, MPH, FRCSC
role: PRINCIPAL_INVESTIGATOR
References: