Efficacy and Safety of Leuprolide Acetate 22.5 mg Depot in Treatment of Prostate Cancer

NCT01415960 | Completed Phase 3 Results

• 1 other identifier: GP/C/05/PRO
• Study Type: interventional
• Target: 163
• Locations: 1 country
• Sites: 25

Brief Summary

Some patients with prostate cancer benefit from androgen deprivation therapy which reduces levels of testosterone. Leuprolide is a synthetic Luteinizing hormone releasing hormone (LHRH) analogue which upon administration can decrease testosterone levels to ≤0.5 ng/mL. Leuprolide Acetate 22.5 mg Depot is a microencapsulated formulation of leuprolide which is released slowly over time and effectively reduces testosterone levels in many patients to ≤0.5 ng/mL for up to three months. In this study Leuprolide acetate 22.5 mg Depot will be administered by intramuscular injection twice over a period of 6 months. The proportion of patients with testosterone ≤0.5 ng/mL evaluated over a period of 168 days.

Conditions

Prostate Cancer

Keywords

Prostate Cancer; androgen deprivation therapy.; Leuprolide Acetate Depot Formulation; Pharmacokinetics; testosterone; serum luteinizing hormone; follicle-stimulating hormone; prostate-specific antigen

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Achieving Chemical Castration (Defined as Testosterone Levels ≤ 0.5 ng/mL) at Days 28, 84, and 168.

  The primary endpoint was testosterone ≤ 0.5 ng/mL assessed on Days 28, 84, and 168. Thereby, maintenance of castration was to be demonstrated through Day 168 with no missing data at these key time points, unless the missing data were due to an event unrelated to the study drug (ITT patients).

  168 days

Secondary Outcomes (6)

• Determination of Serum Luteinizing Hormone (LH)

  168 days

• Follicle-stimulating Hormone (FSH)

  168 days

• Prostate-specific Antigen (PSA) Concentrations

  168 days

• Determination of Leuprolide Cmax

  Cmax1: 0, 1 and 4 hours post-dose on Day 0 and once on Days 2, 14, 28, 56; Cmax2: 0, 1 and 4 hours post-dose on Day 84 and once on Days 86, 112 and 168.

• Safety Endpoints

  168 Days

Study Arms (1)

Leuprolide acetate 22.5 mg depot

EXPERIMENTAL

Leuprolide acetate 22.5 mg depot administered twice, 3 months apart

Drug: Leuprolide acetate 22.5 mg depot, GP-Pharm SA

Interventions

Leuprolide acetate 22.5 mg depot, GP-Pharm SA DRUG

Administered by im injection, twice during the study, three months apart

Leuprolide acetate 22.5 mg depot

Eligibility Criteria

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

You may qualify if:

• Males ≥18 years of age
• Patients with histologically documented prostate carcinoma who might benefit from medical androgen deprivation therapy.
• Life expectancy of at least 1 year.
• WHO/ECOG performance status of 0, 1, or 2.
• Adequate renal function at Screening as defined by serum creatinine ≤1.6 times the upper limit of normal (ULN) for the clinical laboratory.
• Adequate and stable hepatic function as defined by bilirubin ≤1.5 times the ULN and transaminases (i.e., aspartate aminotransferase, alanine aminotransferase) ≤2.5 times the ULN for the clinical laboratory at Screening.
• Ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to cooperate with the investigator and to comply with the requirements of the entire study.
• Following receipt of verbal and written information about the study,the patient must provide signed informed consent before any study related activity is carried out.

You may not qualify if:

• Evidence of brain metastases, in the opinion of the investigator, taking into account medical history, clinical observations, and symptoms (rationale: to minimize possibility of serious acute flare reactions that would necessitate concomitant administration of other drugs).
• Evidence of spinal cord compression, in the opinion of the investigator, taking into account medical history, clinical observations, and symptoms (rationale: see rationale in criterion 1).
• Evidence of severe urinary tract obstruction with threatening urinary retention, in the opinion of the investigator, taking into account medical history, clinical observations, and symptoms (rationale: see rationale in criterion 1).
• Presence of any tumor in the immediate vicinity that could cause spinal cord compression, in the opinion of the investigator, taking into account medical history and clinical observations (rationale: see rationale in criterion 1).
• Excruciating, severe pain from extensive osseous deposits, taking into account medical history, clinical observations, and symptoms (rationale: see rationale in criterion 1).
• Testosterone levels \<1.5 ng/mL at Screening, This testosterone level will be locally determined at the laboratory of each clinical site (rationale: to ensure that all patients have normal baseline testosterone levels).
• Previous androgen ablative therapy lasting more than 6 months, such as LHRH analogues (e.g., Leuprolide acetate, Goserelin, Buserelin) or antagonists (degarelix). Also, therapy must have not occurred within 12 months before the screening visit. Any prior ADT must have not exceeded 6 months of therapy.
• Previous treatment with androgen-receptor blockers, such as Bicalutamide, Flutamide, Megestrol acetate, Ciproterone will only be allowed after a 3 month washout prior to the screening visit (rationale: these therapies alter a patient's androgenic hormonal response for a sustained period).
• Previous orchiectomy, adrenalectomy, or hypophysectomy (no washout allowed) (rationale: these therapies could have altered a patient's androgenic hormonal response).
• Previous prostatic surgery (e.g., radical prostatectomy, transurethral resection of the prostate) within 2 weeks before Baseline (rationale: these therapies could have altered a patient's androgenic hormonal response and/or adverse reaction profile).
• Previous local therapy to the primary tumor with a curative attempt other than surgery (external beam radiotherapy, brachytherapy, thermotherapy, cryotherapy) within 2 weeks before Baseline (rationale: these therapies could have altered a patient's adverse reaction profile).
• Previous cancer systemic therapy such as chemotherapy, immunotherapy (e.g., antibody therapies, tumor vaccines), biological response modifiers (e.g., cytokines).
• Any investigational drug within 5 half-lives of its physiological action or 3 months, whichever is longer, before Baseline (rationale: to prevent adverse effects of another drug being attributed to study drug and to prevent potential interactions).
• Administration of 5-α-reductase inhibitors (Finasteride, Dutasteride) within 3 months before Baseline (rationale: alters PSA levels and androgen metabolism of the prostate cells). Prior use of 5-α-reductase inhibitors will be allowed with a 3 month washout.
• Over-the-counter or alternative medical therapies that have an estrogenic or antiandrogenic effect (i.e., PC-SPES, saw palmetto, Glycyrrhiza, Urinozinc, dehydroepiandrosterone) within the 3 months before Baseline.

Sponsors & Collaborators

• GP-Pharm: lead

Study Sites (25)

Genesis Research

San Diego, California, 92123, United States

Location

Atlantic Urological Associates

Daytona Beach, Florida, 32114, United States

Location

Urology Health Team

Ocala, Florida, 34474, United States

Location

Winter Park Urology Associates, PA

Orlando, Florida, 32803, United States

Location

Coastal Medical Center

Sarasota, Florida, 34237, United States

Location

North Idaho Urology

Coeur d'Alene, Idaho, 83814, United States

Location

Idaho Urologic Institute

Meridian, Idaho, 83642, United States

Location

First Urology

Jeffersonville, Indiana, 47130, United States

Location

Mid Atlantic Clinical Research

Greenbelt, Maryland, 20770, United States

Location

Premier Urology Associates, LLC

Lawrenceville, New Jersey, 08648, United States

Location

The Urological Institute of Northeastern New York

Albany, New York, 12208, United States

Location

Brooklyn Urology Research Group

Brooklyn, New York, 11215, United States

Location

Manhattan Medical Research

New York, New York, 10016, United States

Location

The Premier Medical Group of the Hudson Valley, PC

Poughkeepsie, New York, 12601, United States

Location

Staten Island Urological Research, PC

Staten Island, New York, 10304, United States

Location

PMG Research of Wilmington

Wilmington, North Carolina, 28401, United States

Location

PMG Research of Winston Salem

Winston-Salem, North Carolina, 27103, United States

Location

Urologic Consultants of SE PA

Bala-Cynwyd, Pennsylvania, 19004, United States

Location

Urology Health Specialists, LLC

Bryn Mawr, Pennsylvania, 19010, United States

Location

Greenville Health System

Greer, South Carolina, 29650, United States

Location

Carolina Urologic Research Center

Myrtle Beach, South Carolina, 29572, United States

Location

Urology Associates, PC

Nashville, Tennessee, 37209, United States

Location

Urology San Antonio Research, PA

San Antonio, Texas, 78229, United States

Location

Urology of Virginia

Virginia Beach, Virginia, 23462, United States

Location

Seattle Urology Research Center

Burien, Washington, 98166, United States

Location

Related Publications (1)

• Shore ND, Guerrero S, Sanahuja RM, Gambus G, Parente A. A New Sustained-release, 3-Month Leuprolide Acetate Formulation Achieves and Maintains Castrate Concentrations of Testosterone in Patients With Prostate Cancer. Clin Ther. 2019 Mar;41(3):412-425. doi: 10.1016/j.clinthera.2019.01.004. Epub 2019 Feb 8.

  PMID: 30929678 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Leuprolide

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)

Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins

Results Point of Contact

• Title: Dr. Neal Shore MD
• Organization: Grand Strand Urology Carolina Urology Reseearch Centre

nshore@grandstrandurology.com

+1 843 839 1679

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 11, 2011
• First Posted: August 12, 2011
• Study Start: September 1, 2011
• Primary Completion: May 1, 2013
• Study Completion: November 1, 2013
• Last Updated: March 3, 2017
• Results First Posted: January 18, 2017

Record last verified: 2016-11

Locations

US (25)