Official Title: “A Multicenter, Open-Label, Randomized, Phase III Trial Comparing Immediate Adjuvant Hormonal Therapy (ELIGARD®- Leuprolide Acetate) in Combination With TAXOTERE® (Docetaxel) Administered Every Three Weeks Versus Hormonal Therapy Alone Versus Deferred Therapy Followed by the Same Therapeutic Options in Patients With Prostate Cancer at High Risk of Relapse After Radical Prostatectomy”

Primary Objective : - The primary objective of the study is to compare progression-free survival (PSA progression after systemic treatment, radiologically or histologically documented progression after systemic treatment or death from any cause, whichever occurs first), using a 2x2 factorial design among treatment groups as follows: - Immediate treatment following prostatectomy versus deferred treatment at the time of relapse - Docetaxel q3w plus leuprolide acetate versus leuprolide acetate alone

Secondary Objectives : - To compare the 5-year overall, cancer-specific and metastasis-free survival (metastasis-free survival based on time to clinical evidence of metastasis evidenced by physical exam or radiologically on bone scan or CT scan) after systemic treatment between the groups defined as follows: - Immediate treatment following prostatectomy versus deferred treatment - Docetaxel q3w plus leuprolide acetate versus leuprolide acetate alone - To compare the safety and tolerability between Docetaxel in combination with leuprolide acetate and leuprolide acetate alone. - To evaluate quality of life as measured by the FACT-P questionnaire.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Factorial Assignment, Safety/Efficacy Study

Study Primary Completion Date: November 2010

Intervention(s) in this Clinical Trial

• Drug: leuprolide acetate
  • 22.5 mg SC
• Drug: docetaxel
  • 75 mg/m2 IV

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Treatment Arm I(CHT):
  • docetaxel q3w for 6 cycles in combination with leuprolide acetate every 3 months for 18 months.
• Active Comparator: Treatment Arm I(HT)
  • leuprolide acetate therapy every 3 months for 18 months
• Experimental: Treatment Arm D(CHT)
  • deferred treatment until progression followed by docetaxel q3w in combination with leuprolide acetate every 3 months for 18 months
• Active Comparator: Treatment Arm D(HT)
  • deferred treatment until progression followed by leuprolide acetate every 3 months for 18 months

Primary Measures

• Progression-free survival (PFS)
  • Time Frame: interval from the date of surgery to the date of PSA progression after systemic treatment
    Safety Issue?: No

Secondary Measures

• to compare safety tolerability between Taxotere in combination with Eligard and Eligard alone
  • Time Frame: prior to and/or on specified days during and post treatment
    Safety Issue?: No
• overall survival
  • Time Frame: measured from the date of surgery to the date of death from any cause
    Safety Issue?: No
• cancer-specific survival
  • Time Frame: measured from the date of surgery to the date of death due to prostate cancer
    Safety Issue?: No
• metastasis-free survival
  • Time Frame: measured from date of surgery to date of first clinical evidence of metastasis after protoco systemic treatment, evidenced by physical exam or radiologically on bone scan or CT scanl
    Safety Issue?: No
• to evaluate quality of life as measured by fact questionnaire
  • Time Frame: throughout the study
    Safety Issue?: No

Inclusion Criteria:

• Patients meeting all of the following criteria will be considered for enrollment into the study:
• Pathologically confirmed adenocarcinoma of the prostate based on central pathology review. All other variants are excluded
• Randomization should occur less than 120 days after prostatectomy AND lymphadenectomy.
• A predicted probability of 5-year freedom from progression ≤ 60%, as determined by the postoperative nomogram developed by M. Kattan.
• Bone-scan without evidence of metastasis (within 6 months of randomization)
• Chest x-ray without evidence of metastasis (within 6 months of randomization)
• Abdominal CT Scan without evidence of metastasis (within 6 months of randomization)
• ECOG performance status ≤ 1
• Hematology evaluation within 2 weeks prior to randomization:
• Neutrophils ≥ 2,000/mm3
• Hemoglobin ≥ 10 g/dL
• Platelets ≥ 100,000/mm3
• Hepatic and renal function evaluation within 2 weeks prior to randomization:
• Serum creatinine ≤1.5 × UNL for the institution. If serum creatinine is > 1.5 ×
• UNL, calculate creatinine clearance (should be ≥ 60ml/minute).
• Total serum bilirubin ≤ UNL for the institution. Patients with Gilbert's syndrome may be eligible if indirect serum bilirubin levels at the time of randomization and, at least 6 month prior to randomization, confirm this condition (i.e.
• elevated indirect serum bilirubin).
• SGOT and/or SGPT ≤ 1.5 × institutional UNL if alkaline phosphatase is ≤ UNL OR
• alkaline phosphatase ≤ 5 × UNL if SGOT and SGPT are ≤ UNL
• PSA evaluation within 9 months prior to prostatectomy. However, a 120-day timeframe is recommended
• Post operative PSA necessary for eligibility is defined as a level ≤ 0.2ng/mL using a standard assay at least 30 days after radical prostatectomy and within 7 days prior to randomization. Note that randomization should occur within 120 days after radical prostatectomy
• Serum testosterone ≥ 150ng/dL within 6 months prior to randomization

Exclusion Criteria:

Patients presenting with any of the following will not be included in the study:

• Prior systemic treatment for prostate cancer with hormonal therapy, chemotherapy, or any other anticancer therapy.
• Prior radiation therapy.
• Patients who received, are receiving or scheduled to receive post-operative radiotherapy.
• Patients taking alternative therapies for cancer must stop taking these therapies prior to randomization. Alternative therapies are not allowed during the treatment or follow-up portions of the study. This includes (but is not limited to) alternative therapies such as :
• PC-SPES (all types)
• 5-alpha reductase inhibitors
• Bisphosphonates are to be stopped prior to randomization and are not allowed during the study.
• Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose ( ≤ 20 mg methylprednisolone per day or equivalent).
• History of a malignancy other than prostate cancer. Exceptions to these criteria include:
• patients with adequately treated non-melanoma skin cancers, and
• patients with a history of another malignancy that was curatively treated (including patients with superficial bladder cancer) and who have not had evidence of disease for a minimum of 5 years.
• Peripheral neuropathy ≥ Grade 2.
• ECG with significant abnormalities (as determined by the investigator) within 90 days prior to randomization.
• Patients who are medically unstable, including but not limited to active infection, acute hepatitis, gastrointestinal bleeding, uncontrolled cardiac arrhythmias, interstitial lung disease, inflammatory bowel disease, uncontrolled angina, uncontrolled hypercalcemia, uncompensated congestive heart failure, uncontrolled diabetes, dementia, seizures, superior vena cava syndrome.
• Patients with history of hypersensitivity to polysorbate 80.
• Patients with a known history of viral hepatitis (B, C)
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sanofi-Aventis

Overall Clinical Trial Officials and Contacts

Jean-Philippe Aussel Study Director Sanofi-Aventis  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00283062

Study ID Number: XRP6976J_3501

ClinicalTrials.gov Identifier: NCT00283062

Health Authority: France: Afssaps - French Health Products Safety Agency