MedPath

Leuprolide Acetate 3.75 mg Depot to Treat Prostate Cancer

Phase 3
Completed
Conditions
Prostate Cancer
Registration Number
NCT00128531
Lead Sponsor
GP-Pharm
Brief Summary

The purpose of this study is to look at the efficacy and safety of leuprolide acetate in patients with prostate cancer.

Detailed Description

Other assessments include evaluation of main leuprolide PK parameters in 12 subjects after administration of 3 doses.

Study Design:

This will be a multi-center, open-label, fixed investigation of six monthly dosages of leuprolide acetate 3.75 mg administered to patients with histologically proven carcinoma of prostate, who might benefit from medical androgen deprivation therapy.

A total of 120 male patients will receive a single, i.m. injection of leuprolide acetate 3.75 mg initially on study day 0 (after baseline assessment) and then monthly (i.e. every 28 days) for five months.

12 of the patients will also have plasma leuprolide levels measured for PK analysis during the first 3 injection periods (PK group). These patients will belong to pre-defined study sites.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
120
Inclusion Criteria
  • Males >/= 18 years of age, with histologically proven carcinoma of the prostate, who might benefit from medical androgen deprivation therapy
  • Life expectancy of at least 1 year
  • World Health Organization/Eastern Cooperative Oncology Group (WHO/ECOG) performance status of 0, 1, or 2
  • Adequate renal function at screening as defined by serum creatinine </= 1.6 times the ULN (upper limit of normal) for the clinical laboratory
  • Adequate and stable hepatic function as defined by bilirubin </= 1.5 times the ULN and transaminases (i.e. SGOT, SGPT) </= 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 co-operate with the Investigator and to comply with the requirements of the entire study
  • Signed written informed consent prior to inclusion in the study
Exclusion Criteria
  • Evidence of brain metastases, in the opinion of the Investigator, taking into account medical history, clinical observations and symptoms

  • Evidence of spinal cord compression, in the opinion of the Investigator, taking into account medical history, clinical observations and symptoms

  • 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

  • Excruciating, severe pain from extensive osseous deposits, in the opinion of the Investigator, taking into account medical history, clinical observations and symptoms

  • Testosterone levels < 1.5 ng/mL at screening, locally determined at the laboratory of each clinical site

  • Previous cancer systemic therapy such as chemotherapy, immunotherapy (e.g. antibody therapies, tumor-vaccines), biological response modifiers (e.g. cytokines) within 3 months of baseline

  • Previous hormonal therapy for treatment of prostate cancer, such as luteinising hormone-releasing hormone (LHRH) analogues (e.g. Lupron®, Zoladex®, etc.) [no wash-out allowed]

  • Previous treatment with androgen receptor (AR) blockers, such as Casodex®, Fugerel®, Megace®, Androcur® (no wash-out allowed)

  • Previous orchiectomy, adrenalectomy or hypophysectomy

  • Previous prostatic surgery (e.g. radical prostatectomy, transurethral resection of the prostate [TUR-P]) within 2 weeks of baseline

  • Previous local therapy to the primary tumor with a curative attempt other than surgery (external beam radiotherapy, brachytherapy, thermotherapy, cryotherapy) within 2 weeks of baseline

  • Any investigational drug within 5 half-lives of its physiological action or 3 months (whichever is longer) before baseline

  • Administration of 5-alpha-reductase inhibitors (Proscar®, Avodart®, Propecia®) within 3 months before baseline

  • Over-the-counter (OTC) or alternative medical therapies which have an estrogenic or anti-androgenic effect (i.e., PC-SPES, saw palmetto, Glycyrrhiza®, Urinozinc®, dehydroepiandrosterone [DHEA]) within the 3 months before baseline

  • Hematological parameters (RBC, total and differential WBC count, platelet count, hemoglobin, hematocrit) outside 20% of the upper or lower limits of normal (ULN, LLN) for the clinical laboratory at screening

  • Co-existent malignancy, according to the Investigator's opinion

  • Uncontrolled congestive heart failure, myocardial infarction or a coronary vascular procedure (e.g. balloon angioplasty, coronary artery bypass graft) or significant symptomatic cardiovascular disease(s) within 6 months before baseline; resting uncontrolled hypertension: (>/= 160/100 mmHg) or symptomatic hypotension within 3 months before baseline

  • Venous thrombosis within 6 months of baseline

  • Insulin-dependent diabetes mellitus

  • History of drug and/or alcohol abuse within 6 months of baseline

  • Serious concomitant illness(es) or disease(s) [e.g., hematological, renal, hepatic, respiratory, endocrine, psychiatric] that may interfere with, or put patients at additional risk for, their ability to receive the treatment outlined in the protocol

  • Patients receiving anticoagulants who have prothrombin and partial thromboplastin times outside of the normal range for the laboratory assays; patients who are on anticoagulation or antiplatelet medications (e.g. dipyridamole, ticlopidine, warfarin derivatives) who are not receiving a stable dose for 3 months before baseline; patients who are receiving warfarin-derivative anticoagulants who do not have an International Normalized Ratio (INR) in the therapeutic range for the clinical indication for which the anticoagulant has been prescribed.

  • Blood donations/losses within 2 months of baseline, apart from previous prostatic surgery patients (see earlier exclusion [9]; please note that these patients should not be included in the pharmacokinetic [PK] group)

  • Known hypersensitivity to GnRH, GnRH agonist, including any LHRH analogues, or any excipients of the study formulation

  • History of the following prior to the study:

    • immunization (within 4 weeks of baseline);
    • flu shots (within 2 weeks of baseline);
    • anaphylaxis;
    • skin disease which would interfere with injection site evaluation;
    • dermatographism will be documented at screening and followed up while on treatment.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Primary Outcome Measures
NameTimeMethod
Efficacy: to determine the proportion of patients achieving castration levels of plasma testosterone (defined as <0.5 ng/mL) 4 weeks after the first administration
to determine the proportion of patients maintaining castration levels of plasma testosterone from week 4 to study end
to determine the proportion of patients showing acute rises in plasma testosterone levels upon repeated dosing from week 4 to study end
Safety: evaluation of the safety of the new formulation based on adverse events (AEs), local tolerability, vital signs, electrocardiograms (ECGs), and clinical parameters
Secondary Outcome Measures
NameTimeMethod
Efficacy: determination of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prostate-specific antigen (PSA) concentrations
World Health Organization/Eastern Cooperative Oncology Group (WHO/ECOG) performance status, bone pain, urinary symptoms and urinary pain after administration

Trial Locations

Locations (27)

Florida Urology Specialists

🇺🇸

Sarasota, Florida, United States

Urology Centers of Alabama

🇺🇸

Homewood, Alabama, United States

Carolina Urologic Research Center

🇺🇸

Myrtle Beach, South Carolina, United States

Department of Urology, Semmelweis University

🇭🇺

Budapest, Hungary

Department of Urology, Medical School, University of Pécs

🇭🇺

Pecs, Hungary

Charles University, Clinic of Urology

🇨🇿

Praha, Czech Republic

Sexual Medicine Unit and Urology, Università Vita Salute San Raffaele Fondazione Centro San Raffaele del Monte Tabor

🇮🇹

Milan, Italy

Department of Urology, Technical University of Dresden

🇩🇪

Dresden, Germany

Urology Associates, PC

🇺🇸

Nashville, Tennessee, United States

Department of Urology, Vienna University Medical School

🇦🇹

Vienna, Austria

Urology Department, Hviezdoslavova

🇨🇿

Prague, Czech Republic

Desert Oasis Cancer Center

🇺🇸

Casa Granda, Arizona, United States

Hamilton Urology, P.A.

🇺🇸

Hamilton, New Jersey, United States

Lakeside Urology

🇺🇸

St. Joseph, Michigan, United States

Lawrenceville Urology

🇺🇸

Lawrenceville, New Jersey, United States

AccuMed Research Associates

🇺🇸

Garden City, New York, United States

Urological Surgeons of Long Island

🇺🇸

Garden City, New York, United States

Department of Urology, General Hospital of Bolzano

🇮🇹

Bolzano, Italy

Advanced Research Institute, Inc.

🇺🇸

New Port Richey, Florida, United States

Regional Urology

🇺🇸

Shreveport, Louisiana, United States

Institut Català d'Oncologia, Hospital Duran I Reynals, Servicio de Oncologia Medica

🇪🇸

Barcelona, Spain

Southwest Florida Urologic Associates

🇺🇸

Fort Myers, Florida, United States

Hudson Valley Urology

🇺🇸

Poughkeepsie, New York, United States

Royal Free Hospital and School of Medicine

🇬🇧

London, United Kingdom

Urocentrum Praha

🇨🇿

Prague, Czech Republic

Masaryk Hospital, Urology Dept.

🇨🇿

Usti nad Labem, Czech Republic

Department of Urology, Jessenius Faculty of Medicine, Comenius University

🇸🇰

Martin, Slovakia

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