Clinical Trial Results:
A Single Arm, Open-Label, Phase II Study of Bevacizumab in Combination With Trastuzumab and Capecitabine as First-Line Treatment of Patients With HER2-Positive Locally Recurrent or Metastatic Breast Cancer
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Summary
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EudraCT number |
2008-003283-20 |
Trial protocol |
ES FR SE SK DK |
Global end of trial date |
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Results information
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Results version number |
v1(current) |
This version publication date |
07 May 2016
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First version publication date |
07 May 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MO21926
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00811135 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
F.Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
Roche Trial Information Hotline, F.Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
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Scientific contact |
Roche Trial Information Hotline, F.Hoffmann-La Roche AG, +41 61 6878333, global.trial_information@roche.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Interim
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Date of interim/final analysis |
14 Mar 2013
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
14 Mar 2013
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Global end of trial reached? |
No
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General information about the trial
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Main objective of the trial |
The study was designed to evaluate the efficacy, safety and tolerability of combining bevacizumab with trastuzumab and capecitabine in a single treatment regimen for the treatment of participants with human epidermal growth factor 2 (HER2)-positive locally recurrent or metastatic breast cancer.
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Protection of trial subjects |
This study was fully adhered to the principles outlined in “Guideline for Good Clinical Practice” International Conference on Harmonization (ICH) Tripartite Guideline (January 1997) or with local law.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
29 Dec 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Slovakia: 3
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Country: Number of subjects enrolled |
Spain: 12
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Country: Number of subjects enrolled |
Sweden: 4
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Country: Number of subjects enrolled |
Denmark: 4
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Country: Number of subjects enrolled |
France: 20
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Country: Number of subjects enrolled |
Russian Federation: 45
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Worldwide total number of subjects |
88
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EEA total number of subjects |
43
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
75
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From 65 to 84 years |
13
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Screening details were taken 28 days prior to baseline. There were 88 participants included from 23 centers. | ||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||||
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Arms
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Arm title
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Trastuzumab + Bevacizumab + Capecitabine | ||||||||||||||||||||||||
Arm description |
Participants received intravenous (IV) trastuzumab 8 milligrams per kilogram (mg/kg) for first cycle and then 6 mg/kg for subsequent cycles followed by bevacizumab 15 mg/kg on Day 1 of each treatment cycles along with capecitabine administered orally to participants at a dose of 1000 milligrams per meter square (mg/m^2) twice daily (BID) on Days 1 to 14 of each treatment cycle until disease progression, unmanageable toxicity or participant request for discontinuation. Treatment cycles were of 3 weeks. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Trastuzumab
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Investigational medicinal product code |
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Other name |
Herceptin
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants received IV trastuzumab (8 mg/kg) on Day 1 of first cycle and then 6 mg/kg for subsequent cycles until disease progression, unmanageable toxicity or participant request for discontinuation.
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Investigational medicinal product name |
Bevacizumab
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Investigational medicinal product code |
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Other name |
Avastin
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Pharmaceutical forms |
Solution for injection/infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants received IV bevacizumab (15 mg/kg) on Day 1 of each treatment cycle until disease progression, unmanageable toxicity or participant request for discontinuation.
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Investigational medicinal product name |
Capecitabine
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Investigational medicinal product code |
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Other name |
Xeloda
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Participants received capecitabine (1000 mg/m^2) BID orally on Day 1 to 14 of each treatment cycle until disease progression, unmanageable toxicity or participant request for discontinuation.
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
- | |||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Trastuzumab + Bevacizumab + Capecitabine
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Reporting group description |
Participants received intravenous (IV) trastuzumab 8 milligrams per kilogram (mg/kg) for first cycle and then 6 mg/kg for subsequent cycles followed by bevacizumab 15 mg/kg on Day 1 of each treatment cycles along with capecitabine administered orally to participants at a dose of 1000 milligrams per meter square (mg/m^2) twice daily (BID) on Days 1 to 14 of each treatment cycle until disease progression, unmanageable toxicity or participant request for discontinuation. Treatment cycles were of 3 weeks. | ||
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End point title |
Percentage of Participants with a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) [1] | ||||||||
End point description |
Tumor response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.0. BOR was defined as the best response recorded for a participant from the start of treatment until disease progression/recurrence. Percentage of participants with a BOR of confirmed CR or PR (responders) was reported. CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least a 30 percent (%) decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Confirmed responses were those which were confirmed by a repeat assessment, performed 4 weeks after the criteria for response first met. Intention-to-treat (ITT) population included all participants enrolled in the study who receive at least one dose of any study medication.
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End point type |
Primary
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End point timeframe |
Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analyses have been specified for this primary endpoint due to single arm group study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Disease Progression or Death | ||||||||
End point description |
Disease progression was defined as at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. ITT population.
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End point type |
Secondary
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End point timeframe |
Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression Free Survival (PFS) | ||||||||
End point description |
PFS was defined as the time from enrollment to time of first documented disease progression or death due to any cause, whichever occurred first. Progression: at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. PFS was estimated using Kaplan-Meier methods. ITT population.
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End point type |
Secondary
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End point timeframe |
Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Overall Survival (OS) | ||||||||
End point description |
OS was defined as the time from enrollment to death from any cause where enrollment was defined as successfully passed screening visit, enrolled in the study and received first dose of study treatment. Here, number of participants with OS was reported. ITT population.
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End point type |
Secondary
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End point timeframe |
Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival | ||||||||
End point description |
OS was defined as the time from enrollment to death from any cause where enrollment was defined as successfully passed screening visit, enrolled in the study and received first dose of study treatment. OS was estimated using Kaplan-Meier methods. ITT population.
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End point type |
Secondary
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End point timeframe |
Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Time to Progression (TTP) | ||||||||
End point description |
TTP was defined as the time from enrollment to first documented disease progression. Progression: at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. ITT population.
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End point type |
Secondary
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End point timeframe |
Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Progression (TTP) | ||||||||
End point description |
TTP was defined as the time from enrollment to first documented disease progression. Progression: at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. TTP was estimated using Kaplan-Meier method. ITT population.
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End point type |
Secondary
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End point timeframe |
Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of Participants With Response | ||||||||
End point description |
Participants who had CR or PR were considered as responders. CR: disappearance of all target and non-target lesions and normalization of tumor marker level; PR: at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. ITT population.
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End point type |
Secondary
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End point timeframe |
Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of Response (DR) | ||||||||
End point description |
DR was defined as the time from the first recorded response (CR/PR) to the date of first documented progression or death. CR: disappearance of all target lesions and non-target lesions and normalization of tumor marker level. PR: at least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD. Progression: at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. DR was estimated using Kaplan-Meier methods. ITT population.
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End point type |
Secondary
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End point timeframe |
Screening until disease progression (assessed at screening, every 6 weeks up to Week 36, thereafter every 9 weeks during treatment period, and then every 3 months during follow-up, up to approximately 4 years)
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Up to 28 days after the last study treatment dose (maximum treatment time = approximately 44 months)
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
13.0
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Reporting groups
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Reporting group title |
Trastuzumab + Bevacizumab + Capecitabine
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Reporting group description |
Participants received IV trastuzumab (8 mg/kg) for first cycle and then 6 mg/kg for subsequent cycles followed by bevacizumab (15 mg/kg) on Day 1 of each treatment cycles along with capecitabine administered orally to participants at a dose of 1000 mg/m^2 BID on Days 1 to 14 of each treatment cycle until disease progression, unmanageable toxicity or participant request for discontinuation. Treatment cycles were of 3 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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28 Mar 2012 |
Increased the interval duration between tumor assessments after 24 months of study participation from every 9 weeks to every 15 weeks until disease progression, initiation of alternative anticancer medication or death. Increasing the interval for tumor assessment reduced the number of scans a participant had to undergo. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
