NCT00283062|CompletedPhase 3Results

Adjuvant Leuprolide With or Without Docetaxel in High Risk Prostate Cancer After Radical Prostatectomy

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

Sanofi ClinicalTrials.gov

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2 other identifiers

XRP6976J_3501EudraCT # : 2004-002203-32

Study Type

interventional

Target

228

Locations

16 countries

Sites

Timeline

RegisteredJan 2006

StartedDec 2005

CompletionDec 2010

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 Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

228

participants targeted

Target at P25-P50 for phase_3

Timeline

Completed

Started Dec 2005

Longer than P75 for phase_3

Geographic Reach

16 countries

16 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

5 years study duration

Study Start

First participant enrolled

December 1, 2005

Completed

2 months until next milestone

First Submitted

Initial submission to the registry

January 26, 2006

Completed

1 day until next milestone

First Posted

Study publicly available on registry

January 27, 2006

Completed

4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2010

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2010

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

January 23, 2012

Completed

Last Updated

January 26, 2012

Status Verified

December 1, 2010

Enrollment Period

5 years

First QC Date

January 26, 2006

Results QC Date

December 16, 2011

Last Update Submit

January 25, 2012

Conditions

Prostatic Neoplasms

Outcome Measures

Primary Outcomes (1)

Progression-free Survival (PFS) Assessment - Number of Participants With Disease Progression
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.
from the date of surgery up to 3 years after randomization of the last participant

Secondary Outcomes (5)

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

Study Arms (4)

Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)

EXPERIMENTAL

Participants administered docetaxel every three weeks (q3w) for 6 cycles in combination with leuprolide acetate every 3 months for 18 months immediately following prostatectomy.

Drug: Docetaxel (TAXOTERE®) ChemotherapyDrug: Leuprolide acetate ( ELIGARD®) Hormonal Therapy

Leuprolide Acetate - Immediate Treatment (I-HT)

ACTIVE COMPARATOR

Participants administered leuprolide acetate every 3 months for 18 months immediately following prostatectomy.

Drug: Leuprolide acetate ( ELIGARD®) Hormonal Therapy

Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)

EXPERIMENTAL

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.

Drug: Docetaxel (TAXOTERE®) ChemotherapyDrug: Leuprolide acetate ( ELIGARD®) Hormonal Therapy

Leuprolide Acetate - Deferred Treatment (D-HT)

ACTIVE COMPARATOR

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.

Drug: Leuprolide acetate ( ELIGARD®) Hormonal Therapy

Interventions

Docetaxel (TAXOTERE®) ChemotherapyDRUG

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.

Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)

Leuprolide acetate ( ELIGARD®) Hormonal TherapyDRUG

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.

Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)Leuprolide Acetate - Immediate Treatment (I-HT)

Eligibility Criteria

Age18 Years+

Sexmale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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).
+5 more criteria

You may not qualify if:

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)
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.
+3 more criteria

Contact the study team to confirm eligibility.