Conditions: Prostatic Neoplasms
Allocation: RANDOMIZED | Intervention model: FACTORIAL
Enrollment: 228
Healthy volunteers: no

Brief summary:
This is a prospective, multicenter, open-label, randomized phase III study in participants at high risk of recurrent prostate cancer after radical prostatectomy. The study will investigate

* Treatment with docetaxel (TAXOTERE®) every three weeks (q3w) plus leuprolide acetate (ELIGARD®) versus leuprolide acetate alone (ELIGARD®)
* Immediate treatment following prostatectomy versus deferred treatment at the time of relapse

Using a 2x2 factorial design participants will therefore be randomized to

* Immediate adjuvant treatment with docetaxel plus leuprolide acetate (chemotherapy and hormonal therapy)
* Immediate adjuvant treatment with leuprolide acetate alone (hormonal therapy)
* Deferred treatment with docetaxel plus leuprolide acetate (chemotherapy and hormonal therapy)
* Deferred treatment with leuprolide acetate alone (hormonal therapy)

Primary Objective:

* The primary objective of the study is to compare progression-free survival using a 2x2 factorial design

Secondary Objectives:

* To compare the 5-year overall, cancer-specific and metastasis-free survival after systemic treatment between the groups
* 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.

Originally, 1696 participants were planned in the study (with 424 participants randomized to each arm). However, only a total of 211 participants completed the randomization procedure as of 26 September 2007. Thus, sanofi-aventis, in accordance with the Steering Committee, decided to stop the participant recruitment as of 26 September 2007. Participants who had already signed their Informed Consent (IC) before September 26, 2007 were allowed to enter the randomization if they met eligibility criteria. The final revised number of planned participants to be randomly assigned to the 4 treatment arms was 250, and 228 participants were actually randomized.

The final sample size did not allow all the statistical analyses to be conducted on efficacy data. Therefore, the protocol was amended to reflect the change in the plans for statistical analysis. The study was underpowered to serve as the basis for drawing conclusions regarding efficacy and quality of life (QoL) endpoints.

Detailed description:
The study consisted of the following:

* Randomization of eligible participants within 120 days of prostatectomy
* For participants assigned to immediate therapy, a treatment period up to 18 months within 8 days of randomization
* For participants assigned to deferred treatment, a treatment period up to 18 months after evidence of progression prior to December 2010. Participants who did not progress before December 2010 were withdrawn from the study.

Arms:
arm 1: Participants administered docetaxel every three weeks (q3w) for 6 cycles in combination with leuprolide acetate every 3 months for 18 months immediately following prostatectomy. arm 2: Participants administered leuprolide acetate every 3 months for 18 months immediately following prostatectomy. arm 3: Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with docetaxel every three weeks (q3w) for 6 cycles in combination with leuprolide acetate every 3 months for 18 months. arm 4: Participants in whom treatment was deferred from randomization until first progression - i.e. PSA progression and/or radiologically or histologically documented progression. Participants were treated with with leuprolide acetate every 3 months for 18 months.

Interventions: intervention 1: Docetaxel (TAXOTERE®) Chemotherapy intervention 2: Leuprolide acetate ( ELIGARD®) Hormonal Therapy intervention 3: Docetaxel (TAXOTERE®) Chemotherapy intervention 4: Leuprolide acetate ( ELIGARD®) Hormonal Therapy intervention 5: Leuprolide acetate ( ELIGARD®) Hormonal Therapy
Intervention descriptions: intervention 1: 75 mg/m\^2 docetaxel administered intravenously over 1 hour on Day 1 every three weeks (q3w) for 6 cycles. The first cycle was to be administered within 8 days after randomization.

Corticosteroid pre-medication was mandatory. The following schedule was recommended - 8 mg Dexamethasone orally for 6 doses given - the night before chemotherapy, the morning of chemotherapy, 1 hour before docetaxel infusion, the night of chemotherapy, the morning of the day after chemotherapy and the night of the day after chemotherapy. intervention 2: 22.5 mg leuprolide acetate injection administered subcutaneously (SC) every 3 months for 18 months. The first injection was to be administered within 8 days after randomization. intervention 3: 75 mg/m\^2 docetaxel administered IV over 1 hour on Day 1 q3w for 6 cycles. The first cycle was to be administered within 30 days after progression was confirmed.

Corticosteroid pre-medication was mandatory. The following schedule was recommended - 8 mg Dexamethasone orally for 6 doses given - the night before chemotherapy, the morning of chemotherapy, 1 hour before docetaxel infusion, the night of chemotherapy, the morning of the day after chemotherapy and the night of the day after chemotherapy. intervention 4: 22.5 mg leuprolide acetate injection administered subcutaneously (SC) every 3 months for 18 months. The first injection was to be administered within 30 days after progression is confirmed (on Day 1 of docetaxel administration). intervention 5: 22.5 mg leuprolide acetate injection administered subcutaneously (SC) every 3 months for 18 months. The first injection was to be administered within 30 days after progression is confirmed.

Protocol document: