LIpitor and biGuanide to Androgen Delay Trial (LIGAND)

• ClinicalTrials.gov Identifier: NCT02497638
• Recruitment Status: Not yet recruiting
• First Posted: July 14, 2015
• Last Update Posted: January 13, 2020
• Sponsor: University Health Network, Toronto
• Information provided by (Responsible Party): University Health Network, Toronto

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).

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

Study Design

• 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

Arms and Interventions

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.

Outcome Measures

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.

Eligibility Criteria

• 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

Contacts and Locations

Contacts

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

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

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

More Information

• Responsible Party: University Health Network, Toronto
• ClinicalTrials.gov Identifier: NCT02497638
• Other Study ID Numbers: 15-053
• First Posted: July 14, 2015
• Last Update Posted: January 13, 2020
• Last Verified: January 2020

• 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:

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