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A Study to Evaluate Pertuzumab + Trastuzumab + Docetaxel vs. Placebo + Trastuzumab + Docetaxel in Previously Untreated HER2-positive Metastatic Breast Cancer (CLEOPATRA) (CLEOPATRA)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT00567190
First received: December 3, 2007
Last updated: April 6, 2016
Last verified: April 2016
Results First Received: August 14, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Metastatic Breast Cancer
Interventions: Drug: Pertuzumab
Drug: Placebo
Drug: Trastuzumab
Drug: Docetaxel

  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
No text entered.

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
Pertuzumab + Trastuzumab + Docetaxel Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Placebo + Trastuzumab + Docetaxel Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.

Participant Flow:   Overall Study
    Pertuzumab + Trastuzumab + Docetaxel   Placebo + Trastuzumab + Docetaxel
STARTED   402 [1]   406 [1] 
COMPLETED   192 [2]   142 [3] 
NOT COMPLETED   210   264 
Death                168                221 
Withdrew Consent or Lost to Follow-up                42                43 
[1] All randomized patients (Intent-to-Treat [ITT]) population
[2] On 11 February 2014, 67 were alive and on study treatment; 125 were alive and in survival follow-up
[3] On 11 February 2014, 37 were alive and on study treatment; 105 were alive and in survival follow-up



  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.
ITT population

Reporting Groups
  Description
Pertuzumab + Trastuzumab + Docetaxel Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Placebo + Trastuzumab + Docetaxel Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Total Total of all reporting groups

Baseline Measures
   Pertuzumab + Trastuzumab + Docetaxel   Placebo + Trastuzumab + Docetaxel   Total 
Overall Participants Analyzed 
[Units: Participants]
 402   406   808 
Age 
[Units: Years]
Mean (Standard Deviation)
 53.4  (10.94)   53.5  (11.35)   53.5  (11.14) 
Gender 
[Units: Patients]
     
Female   402   404   806 
Male   0   2   2 


  Outcome Measures
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1.  Primary:   Progression-free Survival (PFS) Determined by an Independent Review Facility   [ Time Frame: Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months) ]

Measure Type Primary
Measure Title Progression-free Survival (PFS) Determined by an Independent Review Facility
Measure Description PFS was defined as the time from randomization to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors (RECIST) or death from any cause (within 18 weeks of last tumor assessment), whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions were selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, were identified as target lesions.
Time Frame Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months)  
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 patients.

Reporting Groups
  Description
Pertuzumab + Trastuzumab + Docetaxel Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Placebo + Trastuzumab + Docetaxel Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.

Measured Values
   Pertuzumab + Trastuzumab + Docetaxel   Placebo + Trastuzumab + Docetaxel 
Participants Analyzed 
[Units: Participants]
 402   406 
Progression-free Survival (PFS) Determined by an Independent Review Facility 
[Units: Months]
Median (95% Confidence Interval)
 18.5 
 (15.0 to 23.0) 
 12.4 
 (10.0 to 13.0) 

No statistical analysis provided for Progression-free Survival (PFS) Determined by an Independent Review Facility



2.  Secondary:   Overall Survival   [ Time Frame: Baseline to the third data cut-off (11 February 2014) at 389 deaths (approximately 43 months after enrollment of the last patient, up to 6 years overall) ]

Measure Type Secondary
Measure Title Overall Survival
Measure Description Overall survival was defined as the time from randomization to death from any cause. The median and 95 percent (%) confidence interval (CI) for time to event were estimated using Kaplan-Meier methodology.
Time Frame Baseline to the third data cut-off (11 February 2014) at 389 deaths (approximately 43 months after enrollment of the last patient, up to 6 years overall)  
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 population: All randomized patients.

Reporting Groups
  Description
Pertuzumab + Trastuzumab + Docetaxel Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Placebo + Trastuzumab + Docetaxel Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.

Measured Values
   Pertuzumab + Trastuzumab + Docetaxel   Placebo + Trastuzumab + Docetaxel 
Participants Analyzed 
[Units: Participants]
 402   406 
Overall Survival 
[Units: Months]
Median (95% Confidence Interval)
 56.5 [1] 
 (49.0 to N/A) 
 40.8 
 (36.0 to 48.0) 
[1] The upper limit of the 95% CI could not be determined as it was larger than the maximum follow-up time.

No statistical analysis provided for Overall Survival



3.  Secondary:   Progression-free Survival (PFS) Determined by the Investigator   [ Time Frame: Baseline to the third data cut-off (11 February 2014) at 389 deaths (approximately 43 months after enrollment of the last patient, up to 6 years overall) ]

Measure Type Secondary
Measure Title Progression-free Survival (PFS) Determined by the Investigator
Measure Description PFS was defined as the time from randomization to first documented disease progression (PD) using Response Evaluation Criteria in Solid Tumors (RECIST) or death from any cause (within 18 weeks of last tumor assessment), whichever occurred first. For target lesions, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Target lesions were selected on the basis of their size (those with the longest diameter) and their suitability for accurate repeated measurements by imaging techniques or clinically. All measurable lesions up to a maximum of 5 lesions per organ and 10 lesions in total, representative of all involved organs, were identified as target lesions.
Time Frame Baseline to the third data cut-off (11 February 2014) at 389 deaths (approximately 43 months after enrollment of the last patient, up to 6 years overall)  
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 population: All randomized patients.

Reporting Groups
  Description
Pertuzumab + Trastuzumab + Docetaxel Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Placebo + Trastuzumab + Docetaxel Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.

Measured Values
   Pertuzumab + Trastuzumab + Docetaxel   Placebo + Trastuzumab + Docetaxel 
Participants Analyzed 
[Units: Participants]
 402   406 
Progression-free Survival (PFS) Determined by the Investigator 
[Units: Months]
Median (95% Confidence Interval)
 18.7 
 (17.0 to 22.0) 
 12.4 
 (10.0 to 14.0) 

No statistical analysis provided for Progression-free Survival (PFS) Determined by the Investigator



4.  Secondary:   Objective Response Determined by an Independent Review Facility   [ Time Frame: Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months) ]

Measure Type Secondary
Measure Title Objective Response Determined by an Independent Review Facility
Measure Description A patient had an objective response if they had a complete response or a partial response determined on two consecutive occasions ≥ 4 weeks apart as determined by the investigator using RECIST. For target lesions, a complete response was defined as the disappearance of all target lesions; a partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter. For non-target lesions, a complete response was defined as the disappearance of all non-target lesions; a partial response was defined as the persistence of 1 or more non-target lesions.
Time Frame Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months)  
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 population: All randomized patients. Only patients with measurable disease at baseline were included in the analysis.

Reporting Groups
  Description
Pertuzumab + Trastuzumab + Docetaxel Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Placebo + Trastuzumab + Docetaxel Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.

Measured Values
   Pertuzumab + Trastuzumab + Docetaxel   Placebo + Trastuzumab + Docetaxel 
Participants Analyzed 
[Units: Participants]
 343   336 
Objective Response Determined by an Independent Review Facility 
[Units: Percentage of patients]
Number (95% Confidence Interval)
 80.2 
 (75.6 to 84.3) 
 69.3 
 (64.1 to 74.2) 

No statistical analysis provided for Objective Response Determined by an Independent Review Facility



5.  Secondary:   Duration of Objective Response Determined by an Independent Review Facility   [ Time Frame: Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months) ]

Measure Type Secondary
Measure Title Duration of Objective Response Determined by an Independent Review Facility
Measure Description Duration of objective response was defined as the time from the initial response to documented disease progression or death from any cause, whichever occurred first.
Time Frame Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months)  
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 population: All randomized patients. Only patients with an objective response were included in the analysis.

Reporting Groups
  Description
Pertuzumab + Trastuzumab + Docetaxel Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Placebo + Trastuzumab + Docetaxel Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.

Measured Values
   Pertuzumab + Trastuzumab + Docetaxel   Placebo + Trastuzumab + Docetaxel 
Participants Analyzed 
[Units: Participants]
 275   233 
Duration of Objective Response Determined by an Independent Review Facility 
[Units: Weeks]
Median (95% Confidence Interval)
 87.6 
 (71.0 to 106.0) 
 54.1 
 (46.0 to 64.0) 

No statistical analysis provided for Duration of Objective Response Determined by an Independent Review Facility



6.  Secondary:   Time to Symptom Progression   [ Time Frame: Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months) ]

Measure Type Secondary
Measure Title Time to Symptom Progression
Measure Description Time to symptom progression was defined as the time from randomization to the first symptom progression as measured by the Functional Assessment of Cancer Therapy-for patients with Breast Cancer (FACT-B) questionnaire with the Trial Outcomes Index-Physical/Functional/Breast (TOI-PFB) subscale. The FACT-B TOI-PFB subscale contains 24 items from 3 subsections of the FACT-B questionnaire: Physical well-being, functional well-being, and additional concerns for breast cancer patients (breast cancer subscale [BCS]). All items in the questionnaire were rated by the patient on a 5-point scale ranging from 0 (“not at all”) to 4 (“very much”). The total score ranged from 0 to 96. A higher score indicates better perceived quality of life. A positive change score from baseline indicates improvement. Symptom progression was defined as a decrease from baseline of 5 points or more.
Time Frame Baseline to primary data cut-off on 13 May 2011 (up to 3 years, 3 months)  
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 population: All randomized patients. Only female patients were included in the analysis.

Reporting Groups
  Description
Pertuzumab + Trastuzumab + Docetaxel Patients received pertuzumab 420 mg intravenously (IV) every 3 weeks (q3w) plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.
Placebo + Trastuzumab + Docetaxel Patients received placebo IV q3w plus trastuzumab 6 mg/kg IV q3w plus docetaxel 75 mg/m^2 IV q3w for at least 6 cycles.

Measured Values
   Pertuzumab + Trastuzumab + Docetaxel   Placebo + Trastuzumab + Docetaxel 
Participants Analyzed 
[Units: Participants]
 402   404 
Time to Symptom Progression 
[Units: Weeks]
Median (95% Confidence Interval)
 18.4 
 (18.0 to 27.0) 
 18.3 
 (18.0 to 27.0) 

No statistical analysis provided for Time to Symptom Progression




  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
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  More Information