LIpitor and biGuanide to Androgen Delay Trial

Prostate Cancer Clinical Trial

— 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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02497638
• Other study ID #: 15-053
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 2021
• Est. completion date: December 2022

Study information

• Verified date: April 2021
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2022
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years to 80 Years

Eligibility

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-a 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

Related Conditions & MeSH terms

• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Metformin
One month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression.
• Atorvastatin
Atorvastatin 20 mg once daily until progression.
• Placebo (corresponding to metformin)
One month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression.
• Placebo (corresponding to atorvastatin)
One placebo tablet (corresponding to atorvastatin) once daily until progression.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		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	Time to androgen deprivation 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.
Secondary	Time to PSA progression		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	Time to disease progression		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	Body mass index	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.
Secondary	Circulating glycated hemoglobin levels	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.
Secondary	C-peptide levels	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.
Secondary	Adipokine levels	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.
Secondary	LDL/HDL cholesterol levels	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.
Secondary	Triglyceride levels	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.
Secondary	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.	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.