LIpitor and biGuanide to Androgen Delay Trial

NCT02497638 | Withdrawn Phase 2 DMC

• 1 other identifier: 15-053
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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).

Conditions

Prostate Cancer

Keywords

metformin; atorvastatin; prostate-specific antigen; biochemical recurrence

Outcome Measures

Primary Outcomes (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.

  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 Outcomes (10)

• 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.

• 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.

• 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.

• Body mass index

  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

  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.

Study Arms (2)

Metformin and Atorvastatin

EXPERIMENTAL

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; Drug: Atorvastatin

Placebo

PLACEBO COMPARATOR

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); Drug: Placebo (corresponding to atorvastatin)

Interventions

Metformin DRUG

One month run-in of 850 mg metformin once daily, followed by 850 mg twice daily of metformin until progression.

Also known as: biguanide

Metformin and Atorvastatin

Atorvastatin DRUG

Atorvastatin 20 mg once daily until progression.

Also known as: lipitor

Metformin and Atorvastatin

Placebo (corresponding to metformin) DRUG

One month of one placebo tablet (corresponding to metformin) once daily, followed by one placebo tablet twice daily until progression.

Placebo

Placebo (corresponding to atorvastatin) DRUG

One placebo tablet (corresponding to atorvastatin) once daily until progression.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Metformin; Biguanides; Atorvastatin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Study Officials

• Robert Hamilton, MD, MPH, FRCSC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

• Neil Fleshner, MD, MPH, FRCSC

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2015
• First Posted: July 14, 2015
• Study Start: December 1, 2021
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2022
• Last Updated: April 19, 2021

Record last verified: 2021-04

Locations

CA (1)