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LIpitor and biGuanide to Androgen Delay Trial (LIGAND)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02497638
Recruitment Status : Not yet recruiting
First Posted : July 14, 2015
Last Update Posted : January 13, 2020
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

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).

Condition or disease Intervention/treatment Phase
Prostate Cancer Drug: Metformin Drug: Atorvastatin Drug: Placebo (corresponding to metformin) Drug: Placebo (corresponding to atorvastatin) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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
Estimated Study Start Date : June 2020
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


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 Name: biguanide

Drug: Atorvastatin
Atorvastatin 20 mg once daily until progression.
Other Name: 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.




Primary Outcome Measures :
  1. 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 Measures :
  1. 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. ]
  2. 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. ]
  3. 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. ]
  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02497638


Contacts
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Contact: Heidi Wagner 416-946-4501 ext 2354 heidi.wagner@uhn.ca
Contact: Miran Kenk 416-946-4501 ext 3431 miran.kenk@uhn.ca

Locations
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Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Principal Investigator: Robert Hamilton, MD, MPH, FRCSC         
Principal Investigator: Neil Fleshner, MD, MPH, FRCSC         
Sponsors and Collaborators
University Health Network, Toronto
Investigators
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Principal Investigator: Robert Hamilton, MD, MPH, FRCSC University Health Network, Toronto
Principal Investigator: Neil Fleshner, MD, MPH, FRCSC University Health Network, Toronto
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT02497638    
Other Study ID Numbers: 15-053
First Posted: July 14, 2015    Key Record Dates
Last Update Posted: January 13, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Health Network, Toronto:
metformin
atorvastatin
prostate-specific antigen
biochemical recurrence
Additional relevant MeSH terms:
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Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Prostatic Diseases
Metformin
Biguanides
Atorvastatin
Hypoglycemic Agents
Physiological Effects of Drugs
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors