Clinical trial NCT00764166: A Prospective Randomized Phase III Study Comparing Hormonal Therapy +/-Docetaxel
Official title: Non-Metastatic High-Risk Prostate Cancer Patients With Biochemical Relapse Only After Local Treatment. A Prospective Randomized Phase III Study Comparing Hormonal Therapy +/-Docetaxel
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Adenocarcinoma of the Prostate
Keywords: PSA (biochemical)
Progression- free Survival
Clinical progress
Overall survival
Tolerance to the treatment
Quality of Live
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: ARTIC group (oncologists and urologists association)
First posted: 2008-10-01
Enrollment: 254
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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).

1. 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
2. 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

Eligibility criteria: 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

Primary outcomes:
measure: 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).
timeFrame: Every month during 5 years.
Secondary outcomes:
measure: Secondary endpoints were metastasis-free survival, PSA response (decrease > 50 % of the PSA), overall survival, cancer specific survival, safety and quality of life (QoL).
timeFrame: Every month during 5 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Service Oncologie Médicale, Hopital Europeen Georges Pompidou
Study officials:
affiliation: European Georges Pompidou Hospital
name: Stephane Oudard, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Oudard S, Latorzeff I, Caty A, Miglianico L, Sevin E, Hardy-Bessard AC, Delva R, Rolland F, Mouret L, Priou F, Beuzeboc P, Gravis G, Linassier C, Gomez P, Voog E, Muracciole X, Abraham C, Banu E, Ferrero JM, Ravaud A, Krakowski I, Lagrange JL, Deplanque G, Zylberait D, Bozec L, Houede N, Culine S, Elaidi R. Effect of Adding Docetaxel to Androgen-Deprivation Therapy in Patients With High-Risk Prostate Cancer With Rising Prostate-Specific Antigen Levels After Primary Local Therapy: A Randomized Clinical Trial. JAMA Oncol. 2019 May 1;5(5):623-632. doi: 10.1001/jamaoncol.2018.6607.