A Study of Avastin (Bevacizumab) in Combination With Herceptin (Trastuzumab) and Xeloda (Capecitabine) in Patients With HER2-Positive Breast Cancer

Study Overview
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Brief Summary
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This single arm study will assess the efficacy and safety of Avastin in combination with Herceptin and Xeloda as first-line treatment of patients with HER2-positive locally recurrent or metastatic breast cancer. Patients will receive 3-weekly treatment cycles of Herceptin (8mg/kg iv on day 1 of first cycle, followed by 6mg/kg iv maintenance dose on day 1 of subsequent cycles), Xeloda (1000mg/m2 bid po on days 1-14 of each treatment cycle) and Avastin (15mg/kg on day 2 of first treatment cycle,and on day 1 of each subsequent cycle).The anticipated time on study treatment is until disease progression, and the target sample size is <100 individuals.

Official Title
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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

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: bevacizumab [Avastin]
* Drug: capecitabine [Xeloda]
* Drug: trastuzumab [Herceptin]


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients, >=18 years of age; breast cancer with measurable locally recurrent or metastatic lesions; candidate for chemotherapy; HER2-positive disease; ECOG PS of <=2. Exclusion Criteria: previous anticancer therapy for metastatic breast cancer; previous radiotherapy for metastatic breast cancer (except for adjuvant radiotherapy >=6 months before enrollment); chronic daily treatment with corticosteroids (>=10mg/day), aspirin (>325 mg/day) or clopidogrel (>75mg/day); other primary tumor within last 5 years, except for adequately treated cervical cancer in situ, squamous or basal cell skin cancer; uncontrolled hypertension or significant cardiovascular disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: bevacizumab [Avastin]<br>* 15mg/kg iv on day 2 of first 3-week cycle,and on day 1 of subsequent cycles<br>Drug: capecitabine [Xeloda]<br>* 1000mg/m2 bid po on days 1-14 of each 3-week cycle<br>Drug: trastuzumab [Herceptin]<br>* 8mg/kg iv loading dose on day 1 of first 3-week cycle, followed by 6mg/kg iv maintenance dose on day 1 of subsequent cycles<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Best Overall Response (BOR) of Confirmed Complete Response (CR) or Partial Response (PR) | 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. | 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Disease Progression or Death | 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. | 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) | 
| Progression Free Survival (PFS) | 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. | 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) | 
| Number of Participants With Overall Survival (OS) | 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. | Screening until death (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) | 
| Overall Survival (OS) | 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. | Screening until death (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) | 
| Number of Participants With Time to Progression (TTP) | TTP was defined as the time from enrollment to first documented disease 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 methods. | 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) | 
| Time to Progression (TTP) | TTP was defined as the time from enrollment to first documented disease 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). | 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) | 
| Number of Participants With Response | 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. | 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) | 
| Duration of Response (DR) | 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. | 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) |