A Study of Bevacizumab (Avastin) in Combination With Capecitabine (Xeloda) in Elderly Patients With Metastatic Colorectal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00484939
First received: June 11, 2007
Last updated: May 28, 2014
Last verified: May 2014
Results First Received: March 7, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Colorectal Cancer
Interventions: Drug: Bevacizumab
Drug: Capecitabine

  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
Bevacizumab + Capecitabine Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Capecitabine Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.

Participant Flow:   Overall Study
    Bevacizumab + Capecitabine     Capecitabine  
STARTED     140     140  
COMPLETED     0     0  
NOT COMPLETED     140     140  
Death                 9                 13  
Adverse Event                 22                 12  
Patient Withdrew Consent                 19                 10  
Protocol Violation                 3                 3  
Lost to Follow-up                 0                 3  
Discretion of Investigator or Sponsor                 7                 3  
Disease progression                 67                 88  
Screen Failure                 2                 2  
Reason Not Specified                 11                 6  



  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.
Intent-to-treat population: All participants randomized into the study.

Reporting Groups
  Description
Bevacizumab + Capecitabine Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Capecitabine Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Total Total of all reporting groups

Baseline Measures
    Bevacizumab + Capecitabine     Capecitabine     Total  
Number of Participants  
[units: participants]
  140     140     280  
Age  
[units: years]
Mean ± Standard Deviation
  76.1  ± 4.18     76.5  ± 3.91     76.3  ± 4.04  
Gender  
[units: participants]
     
Female     56     56     112  
Male     84     84     168  



  Outcome Measures
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1.  Primary:   Progression-free Survival   [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]

Measure Type Primary
Measure Title Progression-free Survival
Measure Description Progression-free survival was defined as the time in months from the date of randomization to the date of disease progression or death from any cause, whichever occurred first. All measurable lesions (maximum of 5 per organ and 10 in total, those with the longest diameter and suitability for accurate repeated measurements) were identified as target lesions (TL). A sum of the longest diameter for all TLs was calculated and reported as the baseline sum longest diameter (SLD). All other lesions were identified as non-TLs and recorded at baseline. PD was defined as ≥ 20% increase in the sum of the longest diameter of TLs, taking as reference the smallest SLD recorded since treatment started, the unequivocal progression of existing non-TLs, or the appearance of 1 or more new lesions.
Time Frame Baseline to the end of the study (up to 5 years 8 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 participants randomized into the study.

Reporting Groups
  Description
Bevacizumab + Capecitabine Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Capecitabine Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.

Measured Values
    Bevacizumab + Capecitabine     Capecitabine  
Number of Participants Analyzed  
[units: participants]
  140     140  
Progression-free Survival  
[units: Months]
Median ( 95% Confidence Interval )
  9.1  
  ( 7.3 to 11.3 )  
  5.1  
  ( 4.3 to 6.3 )  


Statistical Analysis 1 for Progression-free Survival
Groups [1] All groups
Method [2] Log Rank
P Value [3] <0.001
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[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.



2.  Secondary:   Best Overall Response (BOR)   [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]

Measure Type Secondary
Measure Title Best Overall Response (BOR)
Measure Description BOR was defined as the best response (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD], not evaluable [NE], or not assessed [NA]) recorded from the start of study treatment until disease progression (PD) or death. CR was defined as the disappearance of all target (TL) and non-target lesions (non-TL). PR was defined as ≥ 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD, or the persistence of 1 or more non-TLs. For TLs, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD since treatment started. For non-TLs, SD was defined as the persistence of 1 or more lesions. PD was defined as ≥ 20% increase in the sum of the longest diameter of TLs, taking as reference the smallest SLD recorded since treatment started, the unequivocal progression of existing non-TLs, or the appearance of 1 or more new lesions.
Time Frame Baseline to the end of the study (up to 5 years 8 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 participants randomized into the study. Only participants with a response were included in the analysis.

Reporting Groups
  Description
Bevacizumab + Capecitabine Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Capecitabine Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.

Measured Values
    Bevacizumab + Capecitabine     Capecitabine  
Number of Participants Analyzed  
[units: participants]
  140     140  
Best Overall Response (BOR)  
[units: Percentage of participants]
Number ( 95% Confidence Interval )
   
Complete Response     2.9  
  ( 0.8 to 7.2 )  
  1.4  
  ( 0.2 to 5.1 )  
Partial Response     17.1  
  ( 11.3 to 24.4 )  
  8.6  
  ( 4.5 to 14.5 )  
Stable Disease     54.3  
  ( 45.7 to 62.7 )  
  48.6  
  ( 40.0 to 57.2 )  
Progressive Disease     10.0  
  ( 5.6 to 16.2 )  
  21.4  
  ( 14.9 to 29.2 )  
Not assessed     15.7  
  ( 10.1 to 22.8 )  
  20.0  
  ( 13.7 to 27.6 )  


Statistical Analysis 1 for Best Overall Response (BOR)
Groups [1] All groups
Method [2] Fisher Exact
P Value [3] 0.029
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  This statistical analysis compared the number of responders in the 2 treatment groups. A responder was defined as any participant with a best overall response of complete response or partial response. There were 28 responders in the bevacizumab + capecitabine group and 14 responders in the capecitabine group.
[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.



3.  Secondary:   Duration of Response   [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]

Measure Type Secondary
Measure Title Duration of Response
Measure Description Duration of response was defined as the time in months from the first confirmed complete response (CR) or partial response (PR) until disease progression or death from any cause, whichever occurred first. CR was defined as the disappearance of all target (TL) and non-target lesions (non-TL). PR was defined as ≥ 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD, or the persistence of 1 or more non-TLs.
Time Frame Baseline to the end of the study (up to 5 years 8 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 participants randomized into the study. Only participants with a complete response or partial response were included in the analysis.

Reporting Groups
  Description
Bevacizumab + Capecitabine Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Capecitabine Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.

Measured Values
    Bevacizumab + Capecitabine     Capecitabine  
Number of Participants Analyzed  
[units: participants]
  28     14  
Duration of Response  
[units: Months]
Median ( 95% Confidence Interval )
  9.7  
  ( 8.3 to 10.9 )  
  9.4  
  ( 6.2 to 12.6 )  

No statistical analysis provided for Duration of Response



4.  Secondary:   Time to Response   [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]

Measure Type Secondary
Measure Title Time to Response
Measure Description Time to response was defined as the time in months from the date of first study treatment to the date of the first documentation of complete response (CR) or partial response (PR), whichever occurred first. CR was defined as the disappearance of all target (TL) and non-target lesions (non-TL). PR was defined as ≥ 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD, or the persistence of 1 or more non-TLs.
Time Frame Baseline to the end of the study (up to 5 years 8 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 participants randomized into the study.

Reporting Groups
  Description
Bevacizumab + Capecitabine Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Capecitabine Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.

Measured Values
    Bevacizumab + Capecitabine     Capecitabine  
Number of Participants Analyzed  
[units: participants]
  140     140  
Time to Response  
[units: Months]
Median ( 95% Confidence Interval )
  NA  
  ( NA to NA ) [1]
  NA  
  ( 30.4 to NA ) [2]
[1] The median and the lower and upper limits of the 95% confidence interval could not be calculated due to too few events.
[2] The median and the upper limit of the 95% confidence interval could not be calculated due to too few events.

No statistical analysis provided for Time to Response



5.  Secondary:   Overall Survival   [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]

Measure Type Secondary
Measure Title Overall Survival
Measure Description Overall survival was defined as the time in months from randomization to death from any cause.
Time Frame Baseline to the end of the study (up to 5 years 8 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 participants randomized into the study.

Reporting Groups
  Description
Bevacizumab + Capecitabine Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Capecitabine Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.

Measured Values
    Bevacizumab + Capecitabine     Capecitabine  
Number of Participants Analyzed  
[units: participants]
  140     140  
Overall Survival  
[units: Months]
Median ( 95% Confidence Interval )
  20.7  
  ( 16.6 to 26.0 )  
  17.0  
  ( 12.9 to 22.0 )  


Statistical Analysis 1 for Overall Survival
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.130
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[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.



6.  Secondary:   Eastern Cooperative Oncology Group (ECOG) Performance Status   [ Time Frame: Baseline to the Safety Follow-up which occurred 28 days after the last dose of treatment (up to 5 years 8 months). ]

Measure Type Secondary
Measure Title Eastern Cooperative Oncology Group (ECOG) Performance Status
Measure Description The ECOG performance status is a scale used to quantify cancer patients' general well-being and activities of daily life. The scale ranges from 0 to 5, with 0 denoting perfect health and 5 indicating death. The 6 categories are 0=Asymptomatic (Fully active, able to carry on all predisease activities without restriction), 1=Symptomatic but completely ambulatory (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature), 2=Symptomatic, < 50% in bed during the day (Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours), 3=Symptomatic, > 50% in bed, but not bedbound (Capable of only limited self-care, confined to bed or chair 50% or more of waking hours), 4=Bedbound (Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair), 5=Death. Reported is the percentage of participants in each of the 6 ECOG performance status categories.
Time Frame Baseline to the Safety Follow-up which occurred 28 days after the last dose of treatment (up to 5 years 8 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 participants randomized into the study.

Reporting Groups
  Description
Bevacizumab + Capecitabine Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Capecitabine Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.

Measured Values
    Bevacizumab + Capecitabine     Capecitabine  
Number of Participants Analyzed  
[units: participants]
  140     140  
Eastern Cooperative Oncology Group (ECOG) Performance Status  
[units: Percentage of participants]
   
Week 7 ECOG = 0 (n=117,110)     50.4     34.5  
Week 7 ECOG = 1     47.0     58.2  
Week 7 ECOG = 2     1.7     5.5  
Week 7 ECOG = 3     0.9     1.8  
Week 7 ECOG = 4     0.0     0.0  
Week 7 ECOG = 5     0.0     0.0  
Week 16 ECOG = 0 (n=88,77)     50.0     36.4  
Week 16 ECOG = 1     45.5     51.9  
Week 16 ECOG = 2     3.4     11.7  
Week 16 ECOG = 3     1.1     0.0  
Week 16 ECOG = 4     0.0     0.0  
Week 16 ECOG = 5     0.0     0.0  
Week 25 ECOG = 0 (n=66,42)     43.9     45.2  
Week 25 ECOG = 1     48.5     45.2  
Week 25 ECOG = 2     6.1     9.5  
Week 25 ECOG = 3     1.5     0.0  
Week 25 ECOG = 4     0.0     0.0  
Week 25 ECOG = 5     0.0     0.0  
Week 34 ECOG = 0 (n=48,24)     39.6     33.3  
Week 34 ECOG = 1     58.3     58.3  
Week 34 ECOG = 2     0.0     8.3  
Week 34 ECOG = 3     2.1     0.0  
Week 34 ECOG = 4     0.0     0.0  
Week 34 ECOG = 5     0.0     0.0  
Safety Follow-up ECOG = 0 (n=89,82)     33.7     32.9  
Safety Follow-up ECOG = 1     47.2     45.1  
Safety Follow-up ECOG = 2     12.4     14.6  
Safety Follow-up ECOG = 3     6.7     4.9  
Safety Follow-up ECOG = 4     0.0     1.2  
Safety Follow-up ECOG = 5     0.0     1.2  

No statistical analysis provided for Eastern Cooperative Oncology Group (ECOG) Performance Status



7.  Secondary:   Percentage of Participants Requiring Additional Treatment for Malignancy   [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]

Measure Type Secondary
Measure Title Percentage of Participants Requiring Additional Treatment for Malignancy
Measure Description Reported is the percentage of participants requiring additional treatment for malignancy in the survival follow-up period.
Time Frame Baseline to the end of the study (up to 5 years 8 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 participants randomized into the study.

Reporting Groups
  Description
Bevacizumab + Capecitabine Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Capecitabine Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.

Measured Values
    Bevacizumab + Capecitabine     Capecitabine  
Number of Participants Analyzed  
[units: participants]
  140     140  
Percentage of Participants Requiring Additional Treatment for Malignancy  
[units: Percentage of participants]
  50.7     49.3  

No statistical analysis provided for Percentage of Participants Requiring Additional Treatment for Malignancy



8.  Secondary:   Duration of Follow-up   [ Time Frame: Baseline to the end of the study (up to 5 years 8 months) ]

Measure Type Secondary
Measure Title Duration of Follow-up
Measure Description Duration of follow-up is defined as the time in days from randomization until disease progression or death, or time to censoring for overall survival.
Time Frame Baseline to the end of the study (up to 5 years 8 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 participants randomized into the study.

Reporting Groups
  Description
Bevacizumab + Capecitabine Participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3-week treatment cycle. In addition, participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.
Capecitabine Participants received capecitabine 1000 mg/m^2 orally twice daily on Days 1-14 of each 3-week treatment cycle.

Measured Values
    Bevacizumab + Capecitabine     Capecitabine  
Number of Participants Analyzed  
[units: participants]
  140     140  
Duration of Follow-up  
[units: Days]
Mean ± Standard Deviation
  540.5  ± 423.52     479.2  ± 401.01  

No statistical analysis provided for Duration of Follow-up



9.  Secondary:   AEs, Laboratory Parameters, Vital Signs.   [ Time Frame: Throughout study ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  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
No text entered.


  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: Hoffmann-La Roche
phone: 800 821-8590


No publications provided


Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00484939     History of Changes
Other Study ID Numbers: MO19286
Study First Received: June 11, 2007
Results First Received: March 7, 2014
Last Updated: May 28, 2014
Health Authority: Hungary: Ministry of Health