Leuprolide Acetate 3.75 mg Depot to Treat Prostate Cancer

Sponsor

GP-Pharm (Industry)

Overall Status

Completed

CT.gov ID

NCT00128531

Collaborator

(none)

120

Enrollment

Locations

Duration (Months)

4.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Prostate Cancer	Drug: leuprolide acetate	Phase 3

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.

Study Design

Study Type:

Interventional

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Sep 1, 2005

Actual Study Completion Date :

Nov 1, 2007

Outcome Measures

Primary Outcome Measures

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

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 []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Urology Centers of Alabama	Homewood	Alabama	United States	35209
2	Desert Oasis Cancer Center	Casa Granda	Arizona	United States	85222
3	Southwest Florida Urologic Associates	Fort Myers	Florida	United States	33907
4	Advanced Research Institute, Inc.	New Port Richey	Florida	United States	34652
5	Florida Urology Specialists	Sarasota	Florida	United States	34237
6	Regional Urology	Shreveport	Louisiana	United States	71106
7	Lakeside Urology	St. Joseph	Michigan	United States	49085
8	Hamilton Urology, P.A.	Hamilton	New Jersey	United States	08690
9	Lawrenceville Urology	Lawrenceville	New Jersey	United States	08648
10	AccuMed Research Associates	Garden City	New York	United States	11530
11	Urological Surgeons of Long Island	Garden City	New York	United States	11530
12	Hudson Valley Urology	Kingston	New York	United States	12401
13	Hudson Valley Urology	Poughkeepsie	New York	United States	12601
14	Carolina Urologic Research Center	Myrtle Beach	South Carolina	United States	29572
15	Urology Associates, PC	Nashville	Tennessee	United States	37209
16	Department of Urology, Vienna University Medical School	Vienna		Austria	A-1090
17	Urocentrum Praha	Prague		Czech Republic	120 00
18	Urology Department, Hviezdoslavova	Prague		Czech Republic
19	Charles University, Clinic of Urology	Praha		Czech Republic
20	Masaryk Hospital, Urology Dept.	Usti nad Labem		Czech Republic	401 13
21	Department of Urology, Technical University of Dresden	Dresden		Germany	01307
22	Department of Urology, Semmelweis University	Budapest		Hungary	H-1082
23	Department of Urology, Medical School, University of Pécs	Pecs		Hungary	H-7621
24	Department of Urology, General Hospital of Bolzano	Bolzano		Italy	39100
25	Sexual Medicine Unit and Urology, Università Vita Salute San Raffaele Fondazione Centro San Raffaele del Monte Tabor	Milan		Italy	20132
26	Department of Urology, Jessenius Faculty of Medicine, Comenius University	Martin		Slovakia
27	Institut Català d'Oncologia, Hospital Duran I Reynals, Servicio de Oncologia Medica	Barcelona		Spain	08907
28	Royal Free Hospital and School of Medicine	London		United Kingdom	NW3 2QG