A Prospective Randomized Phase III Study Comparing Hormonal Therapy +/-Docetaxel

Study Overview
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Brief Summary
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The primary objective was to evaluate the PSA (biochemical) progression-free survival (PFS) of high-risk metastasis-free PC patients, treated with LH-RH agonist for one year with or without docetaxel after prior radical prostatectomy (RP) or radiotherapy (RT). The study was powered at 80% to detect a 25% improvement in biochemical PFS for a total sample size estimated at 252 patients, with a two-sided type I error rate of 5% (non-parametric methods.

Detailed Description
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Docetaxel was shown to be active in metastatic hormone-refractory prostate cancer (PC) in phase III trials (1-2). It is likely to demonstrate a substantial role in the management of early-stage PC patients in the neoadjuvant and adjuvant settings, where clinical trials are underway.•53% of all men who undergo radical prostatectomy will develop prostate-specific antigen (PSA) elevations in the 10 years following surgery, with approximately 77% of these recurrences occurring within the first 2 years.A prospective, multicenter, national, randomized, two-arm, phase III study comparing hormonal treatment (LH-RH agonist alone) with or without docetaxel was designed to evaluate the interest of chemotherapy in non-metastatic prostate cancer patients at high risk of systemic recurrence after initial treatment (radical prostatectomy or radiotherapy). PETRYLAK DP, et al: Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 351:1513-1520, 2004 TANNOCK IF, de Wit R, Berry WR, et al: Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 351:1502-1512, 2004

Official Title
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Non-Metastatic High-Risk Prostate Cancer Patients With Biochemical Relapse Only After Local Treatment. A Prospective Randomized Phase III Study Comparing Hormonal Therapy +/-Docetaxel

Conditions
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Adenocarcinoma of the Prostate

Intervention / Treatment
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* Drug: Docetaxel + hormonal treatment (LH-RH agonist)
* Drug: Hormonal treatment (LH-RH agonist)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented adenocarcinoma of the prostate Previous treatment with either radical prostatectomy or radiation therapy Salvage radiotherapy for local relapse allowed Neoadjuvant or per radiotherapy Hormonal therapy allowed in case of more than 6 months free-interval before first rising PSA Life expectancy of more than 12 months Non metastatic disease documented by imaging including radionuclide bone scan ECOG performance status 0-1 ANC > 1,500/mm3 Platelet counts > 100,000/mm3 SGOT and/or SGPT may be up to 2.5 x ULN Patients at high risk of biological relapse defined by: Gleason > 8 PSA-DT < 6 months Positive surgical margins PSA velocity > 0.75 ng/mL/year Pathological pelvic lymph nodes involvement (pN+) Time from initial treatment until inclusion < 12 months Exclusion Criteria: Prior chemotherapy by taxanes and estramustine phosphate Documented local recurrence of prostate cancer or documented metastatic disease History of other malignancy within the last 5 years other than curatively treated basal cell carcinoma of the skin Active infection Significant cardiac disease, angina pectoris or myocardial infarction within twelve months Clinically significant neuropathy Medical condition requiring the use of concomitant corticosteroids Prohibited concomitant therapy with experimental drug. Participation in another clinical trial for the period < 30 days

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Docetaxel + hormonal treatment (LH-RH agonist)<br>* Docetaxel will be administered: To D1 of every cycle in the dose of 70 mg/m², Perfusion IV of 60 minutes diluted in 250 ml with physiological serum or with serum glucoside from a peripheral or central vein, Every 3 weeks during 6 cycles (except when unacceptable tolerance). Triptorelin was given by injection for 4 times every 3 months Bicalutamide was given at the same time with LH-RH agonist for 3 weeks ; taken orally<br>|
| Active Comparator: 2<br> | Drug: Hormonal treatment (LH-RH agonist)<br>* Triptorelin was given by injection for 4 times every 3 months. Bicalutamide given at the same time with LH-RH agonist for 3 weeks ; taken orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint was the PSA (biochemical) progression-free survival (PFS) of high-risk metastasis-free PC patients, treated with LH-RH agonist for one year with or without docetaxel after prior radical prostatectomy (RP) or radiotherapy (RT). |  | Every month during 5 years. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary endpoints were metastasis-free survival, PSA response (decrease > 50 % of the PSA), overall survival, cancer specific survival, safety and quality of life (QoL). |  | Every month during 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSA (biochemical), Progression- free Survival, Clinical progress, Overall survival, Tolerance to the treatment, Quality of Live