Back to resultsLIpitor and biGuanide to Androgen Delay Trial (LIGAND)
Primary Purpose
Prostate Cancer
Status
Withdrawn
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Metformin
Atorvastatin
Placebo (corresponding to metformin)
Placebo (corresponding to atorvastatin)
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer focused on measuring metformin, atorvastatin, prostate-specific antigen, biochemical recurrence
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
Sites / Locations
- Princess Margaret Cancer Centre
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Metformin and Atorvastatin
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Time to androgen deprivation therapy
Time to PSA progression
Time to disease progression
Body mass index
Relationship between body mass index and response to anti-metabolic and anti-cholesterol therapy
Circulating glycated hemoglobin levels
Relationship between circulating glycated hemoglobin levels and response to anti-metabolic and anti-cholesterol therapy
C-peptide levels
Relationship between C-peptide levels and response to anti-metabolic and anti-cholesterol therapy
Adipokine levels
Relationship between adipokine levels and response to anti-metabolic and anti-cholesterol therapy
LDL/HDL cholesterol levels
Relationship between LDL/HDL cholesterol levels and response to anti-metabolic and anti-cholesterol therapy
Triglyceride levels
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.
Assessment of incidence of adverse events from the administration of metformin and atorvastatin to men with prostate cancer.
Full Information
NCT ID
NCT02497638
First Posted
June 19, 2015
Last Updated
April 16, 2021
Sponsor
University Health Network, Toronto
1. Study Identification
Unique Protocol Identification Number
NCT02497638
Brief Title
LIpitor and biGuanide to Androgen Delay Trial
Acronym
LIGAND
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
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Drug intervention no longer relevant for the proposed population
Study Start Date
December 2021 (Anticipated)
Primary Completion Date
December 2021 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer
Keywords
metformin, atorvastatin, prostate-specific antigen, biochemical recurrence
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Metformin and Atorvastatin
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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 Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
biguanide
Intervention Description
One month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression.
Intervention Type
Drug
Intervention Name(s)
Atorvastatin
Other Intervention Name(s)
lipitor
Intervention Description
Atorvastatin 20 mg once daily until progression.
Intervention Type
Drug
Intervention Name(s)
Placebo (corresponding to metformin)
Intervention Description
One month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression.
Intervention Type
Drug
Intervention Name(s)
Placebo (corresponding to atorvastatin)
Intervention Description
One placebo tablet (corresponding to atorvastatin) once daily until progression.
Primary Outcome Measure Information:
Title
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 Outcome Measure Information:
Title
Time to 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.
Title
Time to PSA progression
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.
Title
Time to disease progression
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.
Title
Body mass index
Description
Relationship between body mass index and response to anti-metabolic and anti-cholesterol 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.
Title
Circulating glycated hemoglobin levels
Description
Relationship between circulating glycated hemoglobin levels and response to anti-metabolic and anti-cholesterol 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.
Title
C-peptide levels
Description
Relationship between C-peptide levels and response to anti-metabolic and anti-cholesterol 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.
Title
Adipokine levels
Description
Relationship between adipokine levels and response to anti-metabolic and anti-cholesterol 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.
Title
LDL/HDL cholesterol levels
Description
Relationship between LDL/HDL cholesterol levels and response to anti-metabolic and anti-cholesterol 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.
Title
Triglyceride levels
Description
Relationship between triglyceride levels and response to anti-metabolic and anti-cholesterol 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.
Title
Incidence of adverse events during administration of metformin and atorvastatin to men with prostate cancer.
Description
Assessment of incidence of adverse events from the administration of metformin and atorvastatin to men with prostate cancer.
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.
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Hamilton, MD, MPH, FRCSC
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Neil Fleshner, MD, MPH, FRCSC
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
LIpitor and biGuanide to Androgen Delay Trial
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