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

Sponsor

Assistance Publique - Hôpitaux de Paris (Other)

Overall Status

Unknown status

CT.gov ID

NCT00764166

Collaborator

ARTIC group (oncologists and urologists association) (Other)

254

Enrollment

Location

Arms

Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Adenocarcinoma of the Prostate	Drug: Docetaxel + hormonal treatment (LH-RH agonist) Drug: Hormonal treatment (LH-RH agonist)	Phase 3

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).

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

Study Design

Study Type:

Interventional

Actual Enrollment :

254 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Jun 1, 2003

Anticipated Primary Completion Date :

Nov 1, 2009

Anticipated Study Completion Date :

Nov 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Drug: Docetaxel + hormonal treatment (LH-RH agonist) 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
Active Comparator: 2	Drug: Hormonal treatment (LH-RH agonist) 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.

Arm

Intervention/Treatment

Experimental: 1

Drug: Docetaxel + hormonal treatment (LH-RH agonist)

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

Active Comparator: 2

Drug: Hormonal treatment (LH-RH agonist)

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.

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

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