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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00283062




Registration number
NCT00283062
Ethics application status
Date submitted
26/01/2006
Date registered
27/01/2006
Date last updated
26/01/2012

Titles & IDs
Public title
Adjuvant Leuprolide With or Without Docetaxel in High Risk Prostate Cancer 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
Secondary ID [1] 0 0
EudraCT # : 2004-002203-32
Secondary ID [2] 0 0
XRP6976J_3501
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prostatic Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Prostate

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Docetaxel (TAXOTERE®) Chemotherapy
Treatment: Drugs - Leuprolide acetate ( ELIGARD®) Hormonal Therapy
Treatment: Drugs - Docetaxel (TAXOTERE®) Chemotherapy
Treatment: Drugs - Leuprolide acetate ( ELIGARD®) Hormonal Therapy
Treatment: Drugs - Leuprolide acetate ( ELIGARD®) Hormonal Therapy

Experimental: Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT) - Participants administered docetaxel every three weeks (q3w) for 6 cycles in combination with leuprolide acetate every 3 months for 18 months immediately following prostatectomy.

Active Comparator: Leuprolide Acetate - Immediate Treatment (I-HT) - Participants administered leuprolide acetate every 3 months for 18 months immediately following prostatectomy.

Experimental: Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT) - 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.

Active Comparator: Leuprolide Acetate - Deferred Treatment (D-HT) - 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.


Treatment: Drugs: Docetaxel (TAXOTERE®) Chemotherapy
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.

Treatment: Drugs: Leuprolide acetate ( ELIGARD®) Hormonal Therapy
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.

Treatment: Drugs: Docetaxel (TAXOTERE®) Chemotherapy
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.

Treatment: Drugs: Leuprolide acetate ( ELIGARD®) Hormonal Therapy
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).

Treatment: Drugs: Leuprolide acetate ( ELIGARD®) Hormonal Therapy
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) Assessment - Number of Participants With Disease Progression
Timepoint [1] 0 0
from the date of surgery up to 3 years after randomization of the last participant
Secondary outcome [1] 0 0
Median Overall Survival (OS)
Timepoint [1] 0 0
from the date of surgery up to 3 years after randomization of the last participant
Secondary outcome [2] 0 0
Median Cancer-specific Survival (CSS)
Timepoint [2] 0 0
from the date of surgery up to 3 years after randomization of the last participant
Secondary outcome [3] 0 0
Median Metastasis-free Survival (MFS)
Timepoint [3] 0 0
from the date of surgery up to 3 years after randomization of the last participant
Secondary outcome [4] 0 0
To Evaluate Quality of Life (QoL) as Measured Using a Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire
Timepoint [4] 0 0
from 30 days before randomization (baseline) and 18 months after treatment initiation (for change from baseline)
Secondary outcome [5] 0 0
Assessment of Safety and Tolerability - Number of Participants With Adverse Events (AE)
Timepoint [5] 0 0
from treatment initiation up to 19 months after treatment initiation

Eligibility
Key inclusion criteria
Participants who met all of the following criteria were considered for enrollment into the
study.

- Pathologically confirmed adenocarcinoma of the prostate based on central pathology
review. All other variants are excluded

- Randomization should occur less than 120 days after prostatectomy AND lymphadenectomy.

- A predicted probability of 5-year freedom from progression = 60%, as determined by the
postoperative nomogram developed by M. Kattan.

- Bone-scan without evidence of metastasis (within 6 months of randomization)

- Chest x-ray without evidence of metastasis (within 6 months of randomization)

- Abdominal computed tomography (CT) Scan without evidence of metastasis (within 6
months of randomization)

- Eastern Cooperative Oncology Group (ECOG) performance status = 1

- Hematology evaluation within 2 weeks prior to randomization:

- Neutrophils = 2,000/mm3

- Hemoglobin = 10 g/dL

- Platelets = 100,000/mm3

- Hepatic and renal function evaluation within 2 weeks prior to randomization:

- Serum creatinine =1.5 × Upper normal limit (UNL) for the institution. If serum
creatinine is > 1.5 × UNL, calculate creatinine clearance (should be =
60ml/minute).

- Total serum bilirubin = UNL for the institution. Participants 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).

- Serum glutamic oxaloacetic transaminase (SGOT) and/or serum glutamic pyruvic
transaminase (SGPT) = 1.5 × institutional UNL if alkaline phosphatase is = UNL OR

- alkaline phosphatase = 5 × UNL if SGOT and SGPT are = UNL

- Prostate Specific Antigen (PSA) evaluation within 9 months prior to prostatectomy.
However, a 120-day timeframe is recommended

- Post operative PSA necessary for eligibility is defined as a level = 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

- Serum testosterone = 150ng/dL within 6 months prior to randomization.
Minimum age
18 Years
Maximum age
No limit
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Participants presenting with any of the following will not be included in the study.

- Prior systemic treatment for prostate cancer with hormonal therapy, chemotherapy, or
any other anticancer therapy.

- Prior radiation therapy.

- Participants who received, are receiving or scheduled to receive post-operative
radiotherapy.

- Participants 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 :

- PC-SPES (all types)

- 5-alpha reductase inhibitors

- Bisphosphonates are to be stopped prior to randomization and are not allowed during
the study.

- Chronic treatment with corticosteroids unless initiated > 6 months prior to study
entry and at low dose ( = 20 mg methylprednisolone per day or equivalent).

- History of a malignancy other than prostate cancer. Exceptions to these criteria
include:

- participants with adequately treated non-melanoma skin cancers, and

- participants with a history of another malignancy that was curatively treated
(including participants with superficial bladder cancer) and who have not had
evidence of disease for a minimum of 5 years.

- Peripheral neuropathy = Grade 2.

- Electrocardiogram (ECG) with significant abnormalities (as determined by the
investigator) within 90 days prior to randomization.

- Participants 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.

- Participants with history of hypersensitivity to polysorbate 80.

- Participants with a known history of viral hepatitis (B, C).

The above information was not intended to contain all considerations relevant to potential
participation in a clinical trial.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Factorial
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/12/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2010
Sample size
Target
Accrual to date
Final
228
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Sanofi-Aventis Administrative Office - Macquarie Park
Recruitment postcode(s) [1] 0 0
- Macquarie Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
New Jersey
Country [2] 0 0
Austria
State/province [2] 0 0
Vienna
Country [3] 0 0
Brazil
State/province [3] 0 0
Sao Paulo
Country [4] 0 0
Canada
State/province [4] 0 0
Québec
Country [5] 0 0
France
State/province [5] 0 0
Paris
Country [6] 0 0
Germany
State/province [6] 0 0
Frankfurt
Country [7] 0 0
India
State/province [7] 0 0
Mumbai
Country [8] 0 0
Israel
State/province [8] 0 0
Natanya
Country [9] 0 0
Italy
State/province [9] 0 0
Milan
Country [10] 0 0
Mexico
State/province [10] 0 0
Col. Coyoacan
Country [11] 0 0
Netherlands
State/province [11] 0 0
PE Gouda
Country [12] 0 0
Poland
State/province [12] 0 0
Warsaw
Country [13] 0 0
Russian Federation
State/province [13] 0 0
Moscow
Country [14] 0 0
South Africa
State/province [14] 0 0
Gauteng
Country [15] 0 0
Turkey
State/province [15] 0 0
Istanbul
Country [16] 0 0
United Kingdom
State/province [16] 0 0
Guildford Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Sanofi
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00283062
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Jean-Philippe Aussel
Address 0 0
Sanofi
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries