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

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Sanofi

ClinicalTrials.gov Identifier:

NCT00283062

First received: January 26, 2006

Last updated: January 25, 2012

Last verified: December 2010

History of Changes

Results First Received: December 16, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Factorial Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Prostatic Neoplasms
Interventions:	Drug: Docetaxel (TAXOTERE®) Chemotherapy Drug: Leuprolide acetate ( ELIGARD®) Hormonal Therapy

Participant Flow

Hide Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Originally, the study was planned for 1696 participants to be randomized. However, enrollment was not met and in September 2007, the Steering Committee decided to stop recruitment. Only participants who had signed Informed Consent by then and met eligibility criteria were randomized. 228 participants were randomized to this study.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups

	Description
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.
Leuprolide Acetate - Immediate Treatment (I-HT)	Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy.
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.
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.

Participant Flow: Overall Study

	Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	Leuprolide Acetate - Immediate Treatment (I-HT)	Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	Leuprolide Acetate - Deferred Treatment (D-HT)
STARTED	55	55	56	62
ADMINISTERED STUDY TREATMENT	50	51	20	17
COMPLETED HORMONAL THERAPY (6 Cycles)	44	48	15	13
COMPLETED CHEMOTHERAPY (6 Cycles)	43	0 ^[1]	15	0 ^[1]
COMPLETED	43	48	15	13
NOT COMPLETED	12	7	41	49
Did not receive any study medication	5	4	36	45
Adverse Event	2	0	1	0
Lost to Follow-up	1	0	1	0
Progressive disease	0	0	1	0
Participant did not wish to continue	3	2	1	0
Undefined	0	1	1	4
chemotherapy not completed (cycle 6)	1	0	0	0

[1]	Not applicable, since participants in this arm did not receive chemotherapy.

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
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.
Leuprolide Acetate - Immediate Treatment (I-HT)	Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy.
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.
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.
Total	Total of all reporting groups

Baseline Measures

	Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	Leuprolide Acetate - Immediate Treatment (I-HT)	Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	Leuprolide Acetate - Deferred Treatment (D-HT)	Total
Number of Participants [units: participants]	55	55	56	62	228
Age [units: years] Mean ± Standard Deviation	61.2 ± 7.4	61.6 ± 7.0	62.1 ± 7	62.9 ± 7.5	61.9 ± 7.2
Age, Customized [units: participants]
<65 years	37	34	35	35	141
>=65 years	18	21	21	27	87
Gender [units: participants]
Female	0	0	0	0	0
Male	55	55	56	62	228
Race/Ethnicity, Customized [units: participants]
White	48	49	43	59	199
Black	6	3	7	2	18
Asian/Oriental	0	1	4	0	5
Multiracial	0	0	2	0	2
Other	1	2	0	1	4

Outcome Measures

Hide All Outcome Measures

1. 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 ]

Measure Type	Primary
Measure Title	Progression-free Survival (PFS) Assessment - Number of Participants With Disease Progression
Measure 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.
Time Frame	from the date of surgery up to 3 years after randomization of the last participant
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population: all randomized participants, regardless of whether or not they received any study drug.

Reporting Groups

	Description
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.
Leuprolide Acetate - Immediate Treatment (I-HT)	Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy.
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.
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.

Measured Values

	Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	Leuprolide Acetate - Immediate Treatment (I-HT)	Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	Leuprolide Acetate - Deferred Treatment (D-HT)
Number of Participants Analyzed [units: participants]	55	55	56	62
Progression-free Survival (PFS) Assessment - Number of Participants With Disease Progression [units: participants]	10	14	9	8

No statistical analysis provided for Progression-free Survival (PFS) Assessment - Number of Participants With Disease Progression

2. Secondary:

Median Overall Survival (OS) [ Time Frame: from the date of surgery up to 3 years after randomization of the last participant ]

Measure Type	Secondary
Measure Title	Median Overall Survival (OS)
Measure 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.
Time Frame	from the date of surgery up to 3 years after randomization of the last participant
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-treat (ITT) population: all randomized participants, regardless of whether or not they received any drug.

Reporting Groups

	Description
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.
Leuprolide Acetate - Immediate Treatment (I-HT)	Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy.
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.
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.

Measured Values

	Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	Leuprolide Acetate - Immediate Treatment (I-HT)	Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	Leuprolide Acetate - Deferred Treatment (D-HT)
Number of Participants Analyzed [units: participants]	55	55	56	62
Median Overall Survival (OS) [units: participants]	0	2	1	1

No statistical analysis provided for Median Overall Survival (OS)

3. Secondary:

Median Cancer-specific Survival (CSS) [ Time Frame: from the date of surgery up to 3 years after randomization of the last participant ]

Measure Type	Secondary
Measure Title	Median Cancer-specific Survival (CSS)
Measure 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.
Time Frame	from the date of surgery up to 3 years after randomization of the last participant
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Based on a protocol amendment, analysis for Median CSS was not to be performed as the study was underpowered.

Reporting Groups

	Description
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.
Leuprolide Acetate - Immediate Treatment (I-HT)	Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy.
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.
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.

Measured Values

	Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	Leuprolide Acetate - Immediate Treatment (I-HT)	Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	Leuprolide Acetate - Deferred Treatment (D-HT)
Number of Participants Analyzed [units: participants]	0	0	0	0
Median Cancer-specific Survival (CSS) [units: participants]

No statistical analysis provided for Median Cancer-specific Survival (CSS)

4. Secondary:

Median Metastasis-free Survival (MFS) [ Time Frame: from the date of surgery up to 3 years after randomization of the last participant ]

Measure Type	Secondary
Measure Title	Median Metastasis-free Survival (MFS)
Measure 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.
Time Frame	from the date of surgery up to 3 years after randomization of the last participant
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Based on a protocol amendment, analysis for Median MFS was not to be performed as the study was underpowered.

Reporting Groups

	Description
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.
Leuprolide Acetate - Immediate Treatment (I-HT)	Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy.
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.
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.

Measured Values

	Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	Leuprolide Acetate - Immediate Treatment (I-HT)	Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	Leuprolide Acetate - Deferred Treatment (D-HT)
Number of Participants Analyzed [units: participants]	0	0	0	0
Median Metastasis-free Survival (MFS) [units: participants]

No statistical analysis provided for Median Metastasis-free Survival (MFS)

5. Secondary:

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) ]

Measure Type	Secondary
Measure Title	To Evaluate Quality of Life (QoL) as Measured Using a Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire
Measure 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.
Time Frame	from 30 days before randomization (baseline) and 18 months after treatment initiation (for change from baseline)
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
QoL population: The subset of randomized participants who had an evaluable baseline questionnaire and at least one evaluable post-baseline questionnaire. A baseline QoL questionnaire was considered evaluable if it was filled out within 30 days prior to randomization, and no later than the date of randomization.

Reporting Groups

	Description
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.
Leuprolide Acetate - Immediate Treatment (I-HT)	Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy.
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.
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.

Measured Values

	Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	Leuprolide Acetate - Immediate Treatment (I-HT)	Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	Leuprolide Acetate - Deferred Treatment (D-HT)
Number of Participants Analyzed [units: participants]	40	48	15	15
To Evaluate Quality of Life (QoL) as Measured Using a Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire [units: score on a scale] Mean ± Standard Deviation
Baseline	124.0 ± 6.0	121.5 ± 17.8	114.7 ± 13.9	119.7 ± 15.8
Change from Baseline (N=33, N=41, N=12, N=10)	0.7 ± 12.6	1.7 ± 17.2	6.7 ± 15.9	6.1 ± 18.9

No statistical analysis provided for To Evaluate Quality of Life (QoL) as Measured Using a Functional Assessment of Cancer Therapy-Prostate (FACT-P) Questionnaire

6. Secondary:

Assessment of Safety and Tolerability - Number of Participants With Adverse Events (AE) [ Time Frame: from treatment initiation up to 19 months after treatment initiation ]

Measure Type	Secondary
Measure Title	Assessment of Safety and Tolerability - Number of Participants With Adverse Events (AE)
Measure 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.
Time Frame	from treatment initiation up to 19 months after treatment initiation
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety population: all randomized participants who received any study drug

Reporting Groups

	Description
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.
Leuprolide Acetate - Immediate Treatment (I-HT)	Participants administered 22.5 mg leuprolide acetate every 3 months for 18 months immediately following prostatectomy.
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.
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.

Measured Values

	Docetaxel / Leuprolide Acetate - Immediate Treatment (I-CHT)	Leuprolide Acetate - Immediate Treatment (I-HT)	Docetaxel / Leuprolide Acetate - Deferred Treatment (D-CHT)	Leuprolide Acetate - Deferred Treatment (D-HT)
Number of Participants Analyzed [units: participants]	50	51	20	17
Assessment of Safety and Tolerability - Number of Participants With Adverse Events (AE) [units: participants]
with any adverse event (AE)	47	48	19	14
with any serious adverse event (SAE)	12	8	5	2
with an SAE resulting in death	0	0	0	0
with a drug-related AE	47	43	18	10
with a drug-related SAE	6	0	2	0
with AE leading to discontinue all study therapy	2	0	1	0
with AE leading to chemotherapy discontinuation	1	NA ^[1]	1	NA ^[1]
with AE leading to chemotherapy dose reduction	5	NA ^[1]	2	NA ^[1]

[1]	Did not receive chemotherapy

No statistical analysis provided for Assessment of Safety and Tolerability - Number of Participants With Adverse Events (AE)

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: The investigator shall provide the Steering Committee a copy of any manuscript, abstract or oral communication derived from the study for review and comment at least 30 days in advance of any submission. The Sponsor's representatives shall have the right to review and/or delay any publication or presentation to prevent disclosure of Sponsor's confidential information and preserve intellectual property rights.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The study had difficulties in meeting enrollment goals within a reasonable time frame. The final sample size allowed for the safety analyses but was underpowered for drawing conclusions regarding efficacy and quality of life (QoL) endpoints.

Results Point of Contact:

Name/Title: Trial Transparency Team
Organization: Sanofi
e-mail: Contact-Us@sanofi.com

No publications provided

Responsible Party:	Sanofi
ClinicalTrials.gov Identifier:	NCT00283062 History of Changes
Obsolete Identifiers:	NCT00343967
Other Study ID Numbers:	XRP6976J_3501, EudraCT # : 2004-002203-32
Study First Received:	January 26, 2006
Results First Received:	December 16, 2011
Last Updated:	January 25, 2012
Health Authority:	France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

To Top