A Study of Docetaxel Monotherapy or DOXIL and Docetaxel in Patients With Advanced Breast Cancer - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Breast Cancer
Interventions:	Drug: Docetaxel Drug: DOXIL

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
A total of 751 participants were enrolled and randomized at 143 sites in 19 countries.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
751 participants were randomly assigned to 2 treatment groups (Docetaxel: 373 ; DOXIL+docetaxel: 378). 750 participants received treatment (Docetaxel: 373; DOXIL+docetaxel: 377). 1 participant in DOXIL+docetaxel treatment group did not receive treatment.

Reporting Groups

	Description
Docetaxel	Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.
DOXIL+Docetaxel	DOXIL and docetaxel combination: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.

Participant Flow: Overall Study

	Docetaxel	DOXIL+Docetaxel
STARTED	373	378
COMPLETED	4 ^[1]	5 ^[1]
NOT COMPLETED	369	373
Progressive Disease	220	189
Physician Decision	61	58
Withdrawal by Subject	38	46
Adverse Event	29	48
2cycles therapy beyond Complete response	9	16
Death	9	7
Lost to Follow-up	1	3
Not Specified	2	6

[1]	Indicates number of participants on study treatment at time of the primary objective

Baseline Characteristics

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Reporting Groups

	Description
Docetaxel	Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.
DOXIL+Docetaxel	DOXIL and docetaxel combination: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.
Total	Total of all reporting groups

Baseline Measures

	Docetaxel	DOXIL+Docetaxel	Total
Number of Participants [units: participants]	373	378	751
Age [units: years] Mean ± Standard Deviation	52.0 ± 9.23	52.8 ± 9.17	52.4 ± 9.20
Gender [units: Participants]
Female	373	378	751
Male	0	0	0

Outcome Measures

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1. Primary:

Time to Progression [ Time Frame: From date of randomization until date of disease progression or death, whichever occurred first, until approximately 485 events of disease progression or death were observed, as assessed approximately 15 months after the last patient was enrolled ]

Measure Type	Primary
Measure Title	Time to Progression
Measure Description	Time interval in months between the date of randomization and the date of disease progression or death due to progression, whichever occurred first.
Time Frame	From date of randomization until date of disease progression or death, whichever occurred first, until approximately 485 events of disease progression or death were observed, as assessed approximately 15 months after the last patient was enrolled
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: For patients who were progression free at the time of data cutoff, data were censored for time to progression at the time of their last tumor assessment.

Reporting Groups

	Description
Docetaxel	Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.
DOXIL+Docetaxel	DOXIL and docetaxel combination: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.

Measured Values

	Docetaxel	DOXIL+Docetaxel
Number of Participants Analyzed [units: participants]	373	378
Time to Progression [units: Months] Median ( 95% Confidence Interval )	7.0 ( 5.9 to 7.7 )	9.8 ( 8.1 to 10.5 )

Statistical Analysis 1 for Time to Progression

Groups ^[1]	All groups
Method ^[2]	Log Rank
P Value ^[3]	<0.0001
Hazard Ratio (HR) ^[4]	0.65
95% Confidence Interval	( 0.55 to 0.77 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothersis - no difference in Time to Progression (TTP) between the two treatment groups. Designed to detect an improvement in median TTP from 6 months to 7.8 months with 80% power, assuming exponential survival distribution.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

2. Secondary:

Overall Survival [ Time Frame: From the date of randomization until the participant's death from any cause, as assessed until approximately 485 death events were observed which is assessed approximately 25 months after the last patient was enrolled ]

Measure Type	Secondary
Measure Title	Overall Survival
Measure Description	Time interval in months between the date of randomization and the participant's death from any cause.
Time Frame	From the date of randomization until the participant's death from any cause, as assessed until approximately 485 death events were observed which is assessed approximately 25 months after the last patient was enrolled
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: If the date of death was unknown, the data were censored at the date that the participant was last known to have been alive.

Reporting Groups

	Description
Docetaxel	Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.
DOXIL+Docetaxel	DOXIL and docetaxel combination: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.

Measured Values

	Docetaxel	DOXIL+Docetaxel
Number of Participants Analyzed [units: participants]	373	378
Overall Survival [units: Months] Median ( 95% Confidence Interval )	20.7 ( 18.3 to 26.3 )	20.4 ( 19.0 to 23.1 )

Statistical Analysis 1 for Overall Survival

Groups ^[1]	All groups
Method ^[2]	Log Rank
P Value ^[3]	0.5988
Hazard Ratio (HR) ^[4]	1.06
95% Confidence Interval	( 0.86 to 1.3 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null Hypothesis: Designed to detect an improvement in median survival from 15 months to 19.5 months with 80% power.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Not adjusted for multiple comparison.
[4]	Other relevant estimation information:
	No text entered.

3. Secondary:

Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR) [ Time Frame: Up to 30 to 42 days after last dose of study medication ]

Measure Type	Secondary
Measure Title	Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR)
Measure Description	Number of participants in the evaluable population who achieved a CR or PR as per Response Evaluation Criteria In Solid Tumors (RECIST) criteria. CR: Disappearance of all target lesions and PR: at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD. Response was assessed by Computed Tomography (CT)/Magnetic Resonance Imaging (MRI).
Time Frame	Up to 30 to 42 days after last dose of study medication
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.
Evaluable population: Included all randomized participants who received at least 1 dose of study medication (DOXIL or docetaxel), and who had at least 1 postbaseline tumor assessment.

Reporting Groups

	Description
Docetaxel	Docetaxel monotherapy: Docetaxel 75 mg/m2 solution administered by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.
DOXIL+Docetaxel	DOXIL and docetaxel combination: DOXIL 30 mg/m2 solution administered by intravenous infusion, followed by docetaxel 60 mg/m2 administration by intravenous infusion over 1 hour on Day 1 of every 21-day cycle.

Measured Values

	Docetaxel	DOXIL+Docetaxel
Number of Participants Analyzed [units: participants]	364	370
Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR) [units: Participants]	95	129

Statistical Analysis 1 for Response Rate: Number of Participants in the Evaluable Population Who Achieved a Complete Response (CR) or Partial Response (PR)

Groups ^[1]	All groups
Method ^[2]	Cochran-Mantel-Haenszel
P Value ^[3]	0.0085

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Null hypothesis - no difference in response rate between the two treatment groups.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	Not adjusted for multiple comparison

Serious Adverse Events

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Other Adverse Events

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More Information

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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: If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission. Expedited reviews will be arranged if needed. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application. The sponsor will not mandate modifications to scientific content and does not have the right to suppress information.

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
No text entered.

Results Point of Contact:

Name/Title: Director Medical Leader
Organization: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
phone: 908 218 7361 ext NA

No publications provided

Responsible Party:	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:	NCT00091442 History of Changes
Obsolete Identifiers:	NCT00343538
Other Study ID Numbers:	CR004120, DOXILBCA3001
Study First Received:	September 8, 2004
Results First Received:	December 15, 2009
Last Updated:	March 21, 2013
Health Authority:	United States: Food and Drug Administration Ukraine: State Pharmacological Center - Ministry of Health