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

• Register: EUCTR
• Last refreshed on: 10 February 2014
• Main ID: EUCTR2004-002203-32-DE
• Date of registration: 04/11/2005
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis group
• Public 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
• Scientific 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
• Date of first enrolment: 15/02/2006
• Target sample size: 235
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2004-002203-32
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no

Countries of recruitment

Austria, Belgium, Germany, Hungary, Italy, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
Patients meeting all of the following criteria will be considered for enrollment into the study:
1- Pathologically confirmed adenocarcinoma of the prostate based on central pathology review. All other variants are excluded
2- Randomization should occur less than 120 days after prostatectomy AND lymphadenectomy. Patients who didn't undergo lymphadenectomy may be considered for randomization only if they are evaluated at high-risk according to Kattan nomogram (Instructions for Radical Prostatectomy, Appendix H)
3- A predicted probability of 5-year freedom from progression = 60%, as determined by the postoperative nomogram developed by M. Kattan. This probability will be assessed using data from central review of the prostatectomy specimen.
4- Bone-scan without evidence of metastasis (within 6 months of randomization)
5- Chest x-ray without evidence of metastasis (within 6 months of randomization)
6- Abdominal CT Scan without evidence of metastasis (within 6 months of randomization)
7- Age =18 years
8- ECOG performance status = 1 (Appendix A)
9- Hematology evaluation within 2 weeks prior to randomization: a. Neutrophils = 2,000/mm3 b. Hemoglobin = 10 g/dL c. Platelets = 100,000/mm3
10- Hepatic and renal function evaluation within 2 weeks prior to randomization: a. Serum creatinine =1.5 × UNL for the institution. If serum creatinine is > 1.5 × UNL, calculated creatinine clearance (should be = 60ml/minute). b. 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). c. SGOT and/or SGPT =1.5 × institutional UNL if alkaline phosphatase is = UNL OR d. alkaline phosphatase = 5 × UNL if SGOT and SGPT are = UNL
11- PSA evaluation within 9 months prior to prostatectomy. However, a 120-day timeframe is recommended
12- Post operative PSA necessary for eligibility is defined as a level of = 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 (see inclusion criterion 2).
13- Serum testosterone = 150 ng/dL within 6 months prior to randomization.
14- Life expectancy = 5 years
15- Signed, written informed consent prior to randomization.
16- Patients must be accessible for treatment and follow-up. Patients randomized in this trial must be treated and followed at the participating center.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients presenting with any of the following will not be included in the study:
1- Prior systemic treatment for prostate cancer with hormonal therapy, chemotherapy, or any other anticancer therapy.
2- Prior radiation therapy for prostate cancer.
3- Patients who received, are receiving, or scheduled to receive post-operative radiotherapy.
4- 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:
a. PC-SPES (all types)
b. 5-alpha reductase inhibitors
5- Bisphosphonates are to be stopped prior to randomization and are not allowed during the study.
6- Chronic treatment with corticosteroids unless initiated > 6 months prior to study entry and at low dose (= 20 mg methylprednisolone per day or equivalent).
7- History of a malignancy other than prostate cancer. Exceptions to these criteria include:
a. patients with adequately treated non-melanoma skin cancers, and
b. 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.
8- Peripheral neuropathy = Grade 2.
9- ECG with significant abnormalities (as determined by the investigator) within 90 days prior to randomization.
10- Psychological, familial, sociological, or geographical conditions, which do not permit treatment and/or medical follow-up, required to comply with the study protocol.
11- 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.
12- Patients with history of hypersensitivity to polysorbate 80.
13- Patients with a known history of viral hepatitis (B, C)



Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

Prostate Cancer at High Risk of Relapse After Radical Prostatectomy
MedDRA version: 8 Level: PT Classification code 10060862

Intervention(s)

Trade Name: ELIGARD 22,5 mg
Product Name: Eligard 22.5 mg
Pharmaceutical Form: Powder and solvent for solution for injection
INN or Proposed INN: Leuprorelin acetate
Concentration unit: mg milligram(s)
Concentration number: 22.5-

Trade Name: Taxotere 80 mg Konzentrat und Lösungsmittel zur Herstellung einer Infusionslösung
Product Name: Taxotere
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Docetaxel
Concentration unit: mg milligram(s)
Concentration number: 80-

Primary Outcome(s)

Main 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 [Treatment Arms: I(CHT), I(HT)] versus deferred treatment at the time of relapse [Treatment Arms: D(CHT), D(HT)]
• TAXOTERE® q3w plus ELIGARD® (leuprolide acetate) [Treatment Arms: I(CHT), D(CHT)] versus ELIGARD® alone [Treatment Arms: I(HT), D(HT)]

Secondary Objective: The secondary objectives of the study are:
• 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 [Treatment Arms: I(CHT), I(HT)] versus deferred treatment [Treatment Arms: D(CHT), D(HT)]
- TAXOTERE® q3w plus ELIGARD® [Treatment Arms: I(CHT), D(CHT)] versus ELIGARD® alone [Treatment Arms: I (HT), D (HT)]
• To compare the safety and tolerability between TAXOTERE® in combination with ELIGARD® and ELIGARD® alone.
• To evaluate quality of life as measured by the FACT-P questionnaire.

Primary end point(s): The primary analysis variable is progression-free survival (PFS) after protocol-defined systemic therapy.
PFS is defined as the interval from the date of surgery to the date of PSA progression after systemic treatment, date of radiologically or histologically documented progression after systemic treatment or date of death from any cause, whichever occurs first.

Secondary ID(s)

XRP6976J/3501