Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00009674

Trial Description

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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

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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.

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Brief Summary in Scientific Language

The study consisted of the following:

- Randomization of eligible participants within 120 days of prostatectomy

- For participants assigned to immediate therapy, a treatment period up to 18 months
within 8 days of randomization

- For participants assigned to deferred treatment, a treatment period up to 18 months
after evidence of progression prior to December 2010. Participants who did not progress
before December 2010 were withdrawn from the study.

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Organizational Data

  •   DRKS00009674
  •   2015/11/11
  •   2006/01/26
  •   no
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Secondary IDs

  •   2004-002203-32 
  •   NCT00283062  (ClinicalTrials.gov)
  •   XRP6976J_3501  (Sanofi)
  •   EudraCT # : 2004-002203-32 
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Health Condition or Problem studied

  •   Prostatic Neoplasms
  •   C61 -  Malignant neoplasm of prostate
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Interventions/Observational Groups

  •   Drug: Docetaxel (TAXOTERE®) Chemotherapy
  •   Drug: Leuprolide acetate ( ELIGARD®) Hormonal Therapy
  •   Drug: Docetaxel (TAXOTERE®) Chemotherapy
  •   Drug: Leuprolide acetate ( ELIGARD®) Hormonal Therapy
  •   Drug: Leuprolide acetate ( ELIGARD®) Hormonal Therapy
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Active control (effective treament of control group)
  •   Treatment
  •   Factorial
  •   III
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Primary Outcome

- Progression-free Survival (PFS) Assessment - Number of Participants With Disease Progression; time frame: from the date of surgery up to 3 years after randomization of the last participant; PFS is the interval from the date of surgery to date of progression. The date of progression was the earlier of
first PSA increase to ≥ 0.4 ng/mL confirmed within two weeks
date of the nadir, if PSA nadir did not reach < 0.4 ng/mL (for deferred arm)
first radiological/ histological evidence of tumor progression
death. Median PFS was to be estimated using Kaplan-Meier curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Median PFS could not be estimated. Reported is the number of participants with disease progression.

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Secondary Outcome

- Median Overall Survival (OS); time frame: from the date of surgery up to 3 years after randomization of the last participant; Overall survival (OS) was the time interval from the date of surgery to the date of death due to any cause.
Median OS was to be estimated using Kaplan-Meier Curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Moreover, median OS could not be estimated. Reported is the number of participants who died from any cause.
- Median Cancer-specific Survival (CSS); time frame: from the date of surgery up to 3 years after randomization of the last participant; The CSS was the time from the date of surgery to the date of death due to prostate cancer.
Median CSS was to be estimated using Kaplan-Meier curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Therefore, based on a protocol amendment, median CSS was not estimated.
- Median Metastasis-free Survival (MFS); time frame: from the date of surgery up to 3 years after randomization of the last participant; MFS was the interval from the date of surgery to the date of the first clinical evidence of metastasis after treatment initiation. Metastasis was evaluated by a physical exam or radiologically on bone scan or CT scan. Local (palpable) progression, documented histologically or by imaging techniques was considered evidence of progression.
Median MFS was to be estimated using Kaplan-Meier curves. However, enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn. Therefore, based on a protocol amendment, median MFS was not estimated.
- To Evaluate Quality of Life (QoL) as Measured Using a Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire; time frame: from 30 days before randomization (baseline) and 18 months after treatment initiation (for change from baseline); The FACT-P is a 39-item participant questionnaire which assesses physical well-being (7 items), social/family well-being (7 items), emotional well-being (6 items), functional well-being (7 items), and additional prostate cancer specific concerns (12 items). All items are scored from 0 (not at all) to 4 (very much). The total FACT-P score ranges from 0-156, with higher scores representing a better QoL with fewer symptoms. A score of 156 represents the best outcome.
Note: Enrollment was not met, and meaningful conclusions for efficacy or QoL could not be drawn due to the low sample size.
- Assessment of Safety and Tolerability - Number of Participants With Adverse Events (AE); time frame: from treatment initiation up to 19 months after treatment initiation; Number of participants with treatment-emergent adverse events (TEAE). A TEAE was as any adverse event that occurred or worsened during the on-treatment period, which was the period from the day of first infusion of study treatment until 30 days after the last infusion of study treatment.

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Countries of Recruitment

  •   Australia
  •   Austria
  •   Brazil
  •   Canada
  •   France
  •   Germany
  •   India
  •   Israel
  •   Italy
  •   Mexico
  •   Netherlands
  •   Poland
  •   Russian Federation
  •   South Africa
  •   Turkey
  •   United Kingdom
  •   United States
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Locations of Recruitment

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Recruitment

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  •   2005/12/31
  •   228
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Male
  •   18   Years
  •   no maximum age
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Additional 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.

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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.

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Addresses

  • start of 1:1-Block address primary-sponsor
    • Sanofi
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    • Sanofi
    • Jean-Philippe Aussel 
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    • Sanofi
    • Jean-Philippe Aussel 
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Sources of Monetary or Material Support

  • start of 1:1-Block address materialSupport
    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting complete, follow-up complete
  •   2010/12/01
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   2
  •   2016/01/14


* This entry means the parameter is not applicable or has not been set.