LIpitor and biGuanide to Androgen Delay Trial (LIGAND)

April 16, 2021 updated by: University Health Network, Toronto

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

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).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Metformin
One month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression.
Other Names:
  • biguanide
Drug: Atorvastatin
Atorvastatin 20 mg once daily until progression.
Other Names:
  • lipitor
Placebo Comparator: 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.
Drug: Placebo (corresponding to metformin)
One month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression.
Drug: Placebo (corresponding to atorvastatin)
One placebo tablet (corresponding to atorvastatin) once daily until progression.

What is the study measuring?

Primary Outcome Measures

Outcome 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.
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.
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 Measures

Outcome Measure
Measure Description
Time Frame
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.
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
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.
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
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.
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
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.
Relationship between body mass index and response to anti-metabolic and anti-cholesterol 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.
Circulating glycated hemoglobin levels
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.
Relationship between circulating glycated hemoglobin levels and response to anti-metabolic and anti-cholesterol 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.
C-peptide levels
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.
Relationship between C-peptide levels and response to anti-metabolic and anti-cholesterol 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
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.
Relationship between adipokine levels and response to anti-metabolic and anti-cholesterol 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.
LDL/HDL cholesterol levels
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.
Relationship between LDL/HDL cholesterol levels and response to anti-metabolic and anti-cholesterol 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.
Triglyceride levels
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.
Relationship between triglyceride levels and response to anti-metabolic and anti-cholesterol 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.
Incidence of adverse events during 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.
Assessment of incidence of adverse events from the 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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Robert Hamilton, MD, MPH, FRCSC, University Health Network, Toronto
  • Principal Investigator: Neil Fleshner, MD, MPH, FRCSC, University Health Network, Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

December 1, 2021

Primary Completion (Anticipated)

December 1, 2021

Study Completion (Anticipated)

December 1, 2022

Study Registration Dates

First Submitted

June 19, 2015

First Submitted That Met QC Criteria

July 10, 2015

First Posted (Estimate)

July 14, 2015

Study Record Updates

Last Update Posted (Actual)

April 19, 2021

Last Update Submitted That Met QC Criteria

April 16, 2021

Last Verified

April 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-053

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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