A Study to Evaluate the Safety and Efficacy of Bevacizumab in Combination With Chemotherapy in Previously Treated Metastatic Breast Cancer (RIBBON 2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT00281697
First received: January 23, 2006
Last updated: July 5, 2013
Last verified: July 2013
Results First Received: August 23, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Metastatic Breast Cancer
Interventions: Drug: Bevacizumab
Drug: Placebo
Drug: Standard chemotherapy

  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
Standard Chemotherapy + Bevacizumab Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen.
Standard Chemotherapy + Placebo Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen.

Participant Flow:   Overall Study
    Standard Chemotherapy + Bevacizumab     Standard Chemotherapy + Placebo  
STARTED     459     225  
COMPLETED     58     28  
NOT COMPLETED     401     197  
> 60 days since last dose of study drug                 4                 4  
Adverse Event                 54                 15  
Death                 8                 3  
Disease progression                 279                 149  
Not specified                 5                 6  
Physician's decision to withdraw                 15                 12  
Subject/guardian's decision to withdraw                 33                 6  
Did not receive study drug                 3                 2  



  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
Standard Chemotherapy + Bevacizumab Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen.
Standard Chemotherapy + Placebo Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen.
Total Total of all reporting groups

Baseline Measures
    Standard Chemotherapy + Bevacizumab     Standard Chemotherapy + Placebo     Total  
Number of Participants  
[units: participants]
  459     225     684  
Age  
[units: years]
Mean ± Standard Deviation
  55.6  ± 11.0     55.0  ± 11.2     55.4  ± 11.1  
Gender  
[units: participants]
     
Female     457     225     682  
Male     2     0     2  



  Outcome Measures
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1.  Primary:   Progression-free Survival   [ Time Frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months) ]

Measure Type Primary
Measure Title Progression-free Survival
Measure Description PFS was defined as the time from randomization to first documented disease progression (PD) as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, 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 should be 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, should be identified as target lesions.
Time Frame Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 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, regardless of whether they received any study drug or completed the full course of treatment.

Reporting Groups
  Description
Standard Chemotherapy + Bevacizumab Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen.
Standard Chemotherapy + Placebo Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen.

Measured Values
    Standard Chemotherapy + Bevacizumab     Standard Chemotherapy + Placebo  
Number of Participants Analyzed  
[units: participants]
  459     225  
Progression-free Survival  
[units: Months]
Median ( 95% Confidence Interval )
  7.2  
  ( 6.5 to 7.6 )  
  5.1  
  ( 4.1 to 6.0 )  

No statistical analysis provided for Progression-free Survival



2.  Secondary:   Progression-free Survival Within Individual Standard Chemotherapy Cohorts (Taxanes, Gemcitabine, Capecitabine, and Vinorelbine)   [ Time Frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months) ]

Measure Type Secondary
Measure Title Progression-free Survival Within Individual Standard Chemotherapy Cohorts (Taxanes, Gemcitabine, Capecitabine, and Vinorelbine)
Measure Description Progression-free survival was defined as the time from randomization to first documented disease progression as determined by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) or death due to any cause, whichever occurred first. Results are reported for each of the 4 standard chemotherapy cohorts used in the study.
Time Frame Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 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, regardless of whether they received any study drug or completed the full course of treatment.

Reporting Groups
  Description
Standard Chemotherapy + Bevacizumab Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen.
Standard Chemotherapy + Placebo Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen.

Measured Values
    Standard Chemotherapy + Bevacizumab     Standard Chemotherapy + Placebo  
Number of Participants Analyzed  
[units: participants]
  459     225  
Progression-free Survival Within Individual Standard Chemotherapy Cohorts (Taxanes, Gemcitabine, Capecitabine, and Vinorelbine)  
[units: Months]
Median ( 95% Confidence Interval )
   
Taxanes, n=201, 103     8.0  
  ( 7.2 to 9.3 )  
  5.8  
  ( 4.2 to 7.9 )  
Gemcitabine, n=108, 52     6.0  
  ( 5.5 to 7.1 )  
  5.5  
  ( 2.6 to 7.5 )  
Capecitabine, n=97, 47     6.9  
  ( 5.5 to 8.5 )  
  4.1  
  ( 2.8 to 5.1 )  
Vinorelbine, n=53, 23     5.7  
  ( 3.5 to 7.5 )  
  7.0  
  ( 2.7 to 8.9 )  

No statistical analysis provided for Progression-free Survival Within Individual Standard Chemotherapy Cohorts (Taxanes, Gemcitabine, Capecitabine, and Vinorelbine)



3.  Secondary:   Overall Survival   [ Time Frame: Baseline to the end of the study (up to 6 years, 7 months) ]

Measure Type Secondary
Measure Title Overall Survival
Measure Description Overall survival was defined as the time from randomization to death from any cause.
Time Frame Baseline to the end of the study (up to 6 years, 7 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, regardless of whether they received any study drug or completed the full course of treatment.

Reporting Groups
  Description
Standard Chemotherapy + Bevacizumab Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen.
Standard Chemotherapy + Placebo Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen.

Measured Values
    Standard Chemotherapy + Bevacizumab     Standard Chemotherapy + Placebo  
Number of Participants Analyzed  
[units: participants]
  459     225  
Overall Survival  
[units: Months]
Median ( 95% Confidence Interval )
  18.6  
  ( 17.4 to 20.0 )  
  17.8  
  ( 15.1 to 20.4 )  

No statistical analysis provided for Overall Survival



4.  Secondary:   One-year Survival   [ Time Frame: Baseline to the end of the study (up to 6 years, 7 months) ]

Measure Type Secondary
Measure Title One-year Survival
Measure Description Percentage of patients who survived 1 year in the study.
Time Frame Baseline to the end of the study (up to 6 years, 7 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, regardless of whether they received any study drug or completed the full course of treatment.

Reporting Groups
  Description
Standard Chemotherapy + Bevacizumab Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen.
Standard Chemotherapy + Placebo Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen.

Measured Values
    Standard Chemotherapy + Bevacizumab     Standard Chemotherapy + Placebo  
Number of Participants Analyzed  
[units: participants]
  459     225  
One-year Survival  
[units: Percentage of patients]
Number ( 95% Confidence Interval )
  70.5  
  ( 66.3 to 74.7 )  
  68.6  
  ( 62.5 to 74.8 )  

No statistical analysis provided for One-year Survival



5.  Secondary:   Objective Response   [ Time Frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months) ]

Measure Type Secondary
Measure Title Objective Response
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 data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 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, regardless of whether they received any study drug or completed the full course of treatment. Only patients who had measurable disease at baseline were included in the analysis.

Reporting Groups
  Description
Standard Chemotherapy + Bevacizumab Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen.
Standard Chemotherapy + Placebo Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen.

Measured Values
    Standard Chemotherapy + Bevacizumab     Standard Chemotherapy + Placebo  
Number of Participants Analyzed  
[units: participants]
  362     179  
Objective Response  
[units: Percentage of patients]
Number ( 95% Confidence Interval )
  39.5  
  ( 34.4 to 44.7 )  
  29.6  
  ( 23.0 to 36.7 )  

No statistical analysis provided for Objective Response



6.  Secondary:   Duration of Objective Response   [ Time Frame: Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 months) ]

Measure Type Secondary
Measure Title Duration of Objective Response
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. Duration of objective response was only analyzed in patients who achieved an objective response.
Time Frame Baseline to data cut-off for analysis of the primary Outcome Measure (up to 3 years, 2 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, regardless of whether they received any study drug or completed the full course of treatment. Only patients who had measurable disease at baseline and achieved an objective response were included in the analysis.

Reporting Groups
  Description
Standard Chemotherapy + Bevacizumab Patients received one of several standard chemotherapies for metastatic breast cancer plus bevacizumab in a dose of either 10 mg/kg intravenously (IV) every 2 weeks or 15 mg/kg IV every 3 weeks depending upon the schedule of chemotherapy chosen.
Standard Chemotherapy + Placebo Patients received one of several standard chemotherapies for metastatic breast cancer plus placebo to bevacizumab administered IV either every 2 weeks or every 3 weeks depending upon the schedule of chemotherapy chosen.

Measured Values
    Standard Chemotherapy + Bevacizumab     Standard Chemotherapy + Placebo  
Number of Participants Analyzed  
[units: participants]
  143     53  
Duration of Objective Response  
[units: Months]
Median ( 95% Confidence Interval )
  7.3  
  ( 6.2 to 8.2 )  
  7.5  
  ( 6.6 to 9.2 )  

No statistical analysis provided for Duration of Objective Response




  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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  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:
unchecked 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.
unchecked 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.


Results Point of Contact:  
Name/Title: Medical Communications
Organization: Genentech, Inc.
phone: 800 821-8590


No publications provided


Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT00281697     History of Changes
Other Study ID Numbers: AVF3693g
Study First Received: January 23, 2006
Results First Received: August 23, 2012
Last Updated: July 5, 2013
Health Authority: United States: Food and Drug Administration