Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

NCTNCT00283062Other idXRP6976J_3501Other idEudraCT # : 2004-002203-32

Open at ClinicalTrials.govAsk about this trial

Overview

Status: Completed
Phase: Phase 3
Enrollment: 228 participants (actual)
Sponsor: Sanofi · Industry
Design: Randomized · Open label (no masking)
Countries: 17 countries
United States, Australia, Austria, Brazil, Canada, France, Germany, India, Israel, Italy, Mexico, Netherlands, Poland, Russia, South Africa, Turkey (Türkiye), United Kingdom
Start: Dec 2005
Primary completion: Dec 2010
Completion: Dec 2010
First posted: 27 Jan 2006 (estimated)
Last update posted: 26 Jan 2012 (estimated)
Conditions: Prostatic Neoplasms

Timeline

1 trial · 1 completed · 1 with posted results

Completed
Ongoing
Not yet recruiting
Stopped
Estimated dates (est.)
Results posted

2005200620072008200920102011

Ph 3
Adjuvant Leuprolide With or Without Docetaxel in High Risk Prostate Cancer After Radical Prostatectomy
NCT00283062
Dec 2005 to Dec 2010

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

Docetaxel (TAXOTERE®) ChemotherapyDrug
Leuprolide acetate ( ELIGARD®) Hormonal TherapyDrug
Docetaxel (TAXOTERE®) ChemotherapyDrug
Leuprolide acetate ( ELIGARD®) Hormonal TherapyDrug
Leuprolide acetate ( ELIGARD®) Hormonal TherapyDrug

Arms4

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.

Primary outcomes1

Outcomes the sponsor listed as primary.

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
Registry description
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.

Secondary outcomes(5)

Median Overall Survival (OS)
Time frame · from the date of surgery up to 3 years after randomization of the last participant
Registry description
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
Registry description
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
Registry description
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)
Registry description
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
Registry description
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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeNumber· from the date of surgery up to 3 years after randomization of the last participant

Progression-free Survival (PFS) Assessment - Number of Participants With Disease Progression

Group	Value (participants)
Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	10
Leuprolide Acetate - Immediate Treatment (I-HT)	14
Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	9
Leuprolide Acetate - Deferred Treatment (D-HT)	8

Secondary and other outcome results(5)

Secondary outcomeNumber· from the date of surgery up to 3 years after randomization of the last participant

Median Overall Survival (OS)

Group	Value (participants)
Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	0
Leuprolide Acetate - Immediate Treatment (I-HT)	2
Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	1
Leuprolide Acetate - Deferred Treatment (D-HT)	1

Secondary outcomeNumber· from the date of surgery up to 3 years after randomization of the last participant

Median Cancer-specific Survival (CSS)

Group	Value (participants)
Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	not posted
Leuprolide Acetate - Immediate Treatment (I-HT)	not posted
Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	not posted
Leuprolide Acetate - Deferred Treatment (D-HT)	not posted

Secondary outcomeNumber· from the date of surgery up to 3 years after randomization of the last participant

Median Metastasis-free Survival (MFS)

Group	Value (participants)
Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	not posted
Leuprolide Acetate - Immediate Treatment (I-HT)	not posted
Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	not posted
Leuprolide Acetate - Deferred Treatment (D-HT)	not posted

Secondary outcomeMean· from 30 days before randomization (baseline) and 18 months after treatment initiation (for change from baseline)

To Evaluate Quality of Life (QoL) as Measured Using a Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire

Group	Value (score on a scale)	Spread
Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	124.0	6.0
Leuprolide Acetate - Immediate Treatment (I-HT)	121.5	17.8
Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	114.7	13.9
Leuprolide Acetate - Deferred Treatment (D-HT)	119.7	15.8

Secondary outcomeNumber· from treatment initiation up to 19 months after treatment initiation

Assessment of Safety and Tolerability - Number of Participants With Adverse Events (AE)

Group	Value (participants)
Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	47
Leuprolide Acetate - Immediate Treatment (I-HT)	48
Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	19
Leuprolide Acetate - Deferred Treatment (D-HT)	14

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
Group	Deaths	Serious events	Other events
Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)Participants administered 75 mg/m\^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy.	–	12 / 50	47 / 50
Leuprolide Acetate - Immediate Treatment (I-HT)Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy.	–	8 / 51	48 / 51
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 75 mg/m\^2 docetaxel every three weeks (q3w) for 6 cycles in combination with 22.5 mg leuprolide acetate every 3 months for 18 months.	–	5 / 20	19 / 20
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 22.5 mg leuprolide acetate every 3 months for 18 months.	–	2 / 17	13 / 17

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies0

Studies that cite this trial.

No study cites this trial.

Eligibility

Who could join, as posted.

Sex: Male
Age: from 18 Years
Healthy volunteers: Not accepted

Inclusion and exclusion criteria, as posted

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. 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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