Clinical trial NCT00128531: Leuprolide Acetate 3.75 mg Depot to Treat Prostate Cancer
Official title: Efficacy and Safety of a New Leuprolide Acetate 3.75 mg Depot Formulation, GP-Pharm S.A., When Given as Palliative Treatment to Prostate Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Prostate Cancer
Keywords: Phase III
open label
multiple dose
safety study
pharmacokinetic study
efficacy study
Lead sponsor: GP-Pharm
Sponsor class: INDUSTRY
First posted: 2005-08-10
Enrollment: 120
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
measure: to determine the proportion of patients maintaining castration levels of plasma testosterone from week 4 to study end
measure: to determine the proportion of patients showing acute rises in plasma testosterone levels upon repeated dosing from week 4 to study end
measure: Safety: evaluation of the safety of the new formulation based on adverse events (AEs), local tolerability, vital signs, electrocardiograms (ECGs), and clinical parameters
Secondary outcomes:
measure: Efficacy: determination of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prostate-specific antigen (PSA) concentrations
measure: World Health Organization/Eastern Cooperative Oncology Group (WHO/ECOG) performance status, bone pain, urinary symptoms and urinary pain after administration
Other outcomes:
Locations:
city: Homewood
country: United States
facility: Urology Centers of Alabama
state: Alabama
city: Casa Granda
country: United States
facility: Desert Oasis Cancer Center
state: Arizona
city: Fort Myers
country: United States
facility: Southwest Florida Urologic Associates
state: Florida
city: New Port Richey
country: United States
facility: Advanced Research Institute, Inc.
state: Florida
city: Sarasota
country: United States
facility: Florida Urology Specialists
state: Florida
city: Shreveport
country: United States
facility: Regional Urology
state: Louisiana
city: St. Joseph
country: United States
facility: Lakeside Urology
state: Michigan
city: Hamilton
country: United States
facility: Hamilton Urology, P.A.
state: New Jersey
city: Lawrenceville
country: United States
facility: Lawrenceville Urology
state: New Jersey
city: Garden City
country: United States
facility: AccuMed Research Associates
state: New York
city: Garden City
country: United States
facility: Urological Surgeons of Long Island
state: New York
city: Kingston
country: United States
facility: Hudson Valley Urology
state: New York
city: Poughkeepsie
country: United States
facility: Hudson Valley Urology
state: New York
city: Myrtle Beach
country: United States
facility: Carolina Urologic Research Center
state: South Carolina
city: Nashville
country: United States
facility: Urology Associates, PC
state: Tennessee
city: Vienna
country: Austria
facility: Department of Urology, Vienna University Medical School
city: Prague
country: Czech Republic
facility: Urocentrum Praha
city: Prague
country: Czech Republic
facility: Urology Department, Hviezdoslavova
city: Praha
country: Czech Republic
facility: Charles University, Clinic of Urology
city: Usti nad Labem
country: Czech Republic
facility: Masaryk Hospital, Urology Dept.
city: Dresden
country: Germany
facility: Department of Urology, Technical University of Dresden
city: Budapest
country: Hungary
facility: Department of Urology, Semmelweis University
city: Pecs
country: Hungary
facility: Department of Urology, Medical School, University of Pécs
city: Bolzano
country: Italy
facility: Department of Urology, General Hospital of Bolzano
city: Milan
country: Italy
facility: Sexual Medicine Unit and Urology, Università Vita Salute San Raffaele Fondazione Centro San Raffaele del Monte Tabor
city: Martin
country: Slovakia
facility: Department of Urology, Jessenius Faculty of Medicine, Comenius University
city: Barcelona
country: Spain
facility: Institut Català d'Oncologia, Hospital Duran I Reynals, Servicio de Oncologia Medica
city: London
country: United Kingdom
facility: Royal Free Hospital and School of Medicine
Study officials:
References:
citation: Marberger M, Kaisary AV, Shore ND, Karlin GS, Savulsky C, Mis R, Leuratti C, Germa JR. Effectiveness, pharmacokinetics, and safety of a new sustained-release leuprolide acetate 3.75-mg depot formulation for testosterone suppression in patients with prostate cancer: a Phase III, open-label, international multicenter study. Clin Ther. 2010 Apr;32(4):744-57. doi: 10.1016/j.clinthera.2010.04.013.