Adjuvant Leuprolide With or Without Docetaxel in High Risk Prostate Cancer After Radical Prostatectomy

Condition(s) targeted: Prostatic Neoplasms

Intervention: leuprolide acetate (Drug); docetaxel in combination with leuprolide acetate (Drug); leuprolide acetate (Drug); docetaxel in combination with leuprolide acetate (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: Sanofi-Aventis

Official(s) and/or principal investigator(s):
Jean-Philippe Aussel, Study Director, Affiliation: Sanofi-Aventis

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.

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

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

Primary outcome:

Progression-free survival (PFS)

overall survival

Cancer-specific survival

metastasis-free survival

Secondary outcome: Adverse events recorded using the NCI-CTCAE

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Male.

Criteria:

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.

Sanofi-Aventis, North Ryde, Australia

Sanofi-Aventis, Vienna, Austria

Sanofi-Aventis, Brussels, Belgium

Sanofi-Aventis, Sao Paulo, Brazil

Sanofi-Aventis, Laval, Canada

Sanofi-Aventis, Paris, France

Sanofi-Aventis, Berlin, Germany

Sanofi-Aventis, Mumbai, India

Sanofi-Aventis, Natanya, Israel

Sanofi-Aventis, Milan, Italy

Sanofi-Aventis, Mexico, Mexico

Sanofi-Aventis, Gouda, Netherlands

Sanofi-Aventis, Warsaw, Poland

Sanofi-Aventis, Moscow, Russian Federation

Sanofi-Aventis, Johannesburg, South Africa

Sanofi-Aventis, Istanbul, Turkey

Sanofi-Aventis, Guildford, United Kingdom

Sanofi-Aventis, Bridgewater, New Jersey, United States

Starting date: January 2006
Last updated: April 10, 2008