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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00091442
First received: September 8, 2004
Last updated: April 2, 2014
Last verified: April 2014
Results First Received: December 15, 2009  
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
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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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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.
No text entered.

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 method 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 method 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 method 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


  Other Adverse Events


  Limitations and Caveats
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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
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