A Study of Bevacizumab (Avastin) in Women With HER2 Negative Metastatic Breast Cancer

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of 2 doses of Avastin in combination with docetaxel, versus docetaxel plus placebo, in patients with metastatic HER2 negative breast cancer who are candidates for taxane-based chemotherapy but who have not received prior chemotherapy for metastatic disease. The anticipated time on treatment is 1-2 years and the target sample size is 500+ individuals.

Detailed Description
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Five participants randomized to the docetaxel 100 mg/m^2 plus placebo group actually received docetaxel 100 mg/m^2 plus bevacizumab 7.5 mg/kg and are included in the docetaxel 100 mg/m^2 plus bevacizumab 7.5 mg/kg group for the adverse event results. Sixteen participants randomized to the docetaxel 100 mg/m^2 plus placebo group actually received docetaxel 100 mg/m^2 plus bevacizumab 15.0 mg/kg and are included in the docetaxel 100 mg/m^2 plus bevacizumab 15.0 mg/kg group for the adverse event results.

Official Title
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A Randomised, Double Blind, Placebo Controlled, Multicentre Study to Evaluate the Efficacy and Safety of Bevacizumab in Combination With Docetaxel in Comparison With Docetaxel Plus Placebo, as First Line Treatment for Patients With HER2 Negative Metastatic and Locally Recurrent Breast Cancer.

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Placebo to bevacizumab
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Female patients ≥ 18 years of age. Human epidermal growth factor receptor 2 (HER2)-negative cancer of the breast with locally recurrent or metastatic disease, suitable for chemotherapy. No adjuvant chemotherapy within 6 months before randomization, and no taxane-based chemotherapy within 12 months before randomization. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Exclusion criteria: Previous chemotherapy for metastatic or locally recurrent breast cancer. Radiotherapy for treatment of metastatic disease. Other primary tumors within last 5 years, except for controlled limited basal cell or squamous cancer of the skin, or cancer in situ of the cervix. Spinal cord compression or brain metastases. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to randomization. Inadequate bone marrow, liver, or renal function. Uncontrolled hypertension.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Docetaxel 100 mg/m^2 plus placebo<br>Participants received docetaxel 100 mg/m^2 intravenously on Day 1 of each 3 week cycle for a maximum of 27 weeks (9 cycles). In addition, participants received placebo to bevacizumab intravenously on Day 1 of each 3 week cycle until disease progression, unacceptable toxicity, or participant withdrawal. | Drug: Docetaxel<br>* Docetaxel was supplied in 2 vials, 1 containing docetaxel and 1 containing a solvent, for intravenous infusion.<br>Drug: Placebo to bevacizumab<br>* Placebo to bevacizumab was supplied as a sterile liquid for intravenous infusion in single-use vials.<br>|
| Experimental: Docetaxel 100 mg/m^2 plus bevacizumab 7.5 mg/kg<br>Participants received docetaxel 100 mg/m^2 intravenously on Day 1 of each 3 week cycle for a maximum of 27 weeks (9 cycles). In addition, participants received bevacizumab 7.5 mg/kg intravenously on Day 1 of each 3 week cycle until disease progression, unacceptable toxicity, or participant withdrawal. | Drug: Docetaxel<br>* Docetaxel was supplied in 2 vials, 1 containing docetaxel and 1 containing a solvent, for intravenous infusion.<br>Drug: Bevacizumab<br>* Bevacizumab was supplied as a sterile liquid for intravenous infusion in single-use vials.<br>* Other names: Avastin;|
| Experimental: Docetaxel 100 mg/m^2 plus bevacizumab 15.0 mg/kg<br>Participants received docetaxel 100 mg/m^2 intravenously on Day 1 of each 3 week cycle for a maximum of 27 weeks (9 cycles). In addition, participants received bevacizumab 15.0 mg/kg intravenously on Day 1 of each 3 week cycle until disease progression, unacceptable toxicity, or participant withdrawal. | Drug: Docetaxel<br>* Docetaxel was supplied in 2 vials, 1 containing docetaxel and 1 containing a solvent, for intravenous infusion.<br>Drug: Bevacizumab<br>* Bevacizumab was supplied as a sterile liquid for intravenous infusion in single-use vials.<br>* Other names: Avastin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Progression-free survival was evaluated using Response Evaluation Criteria In Solid Tumors (RECIST 1.0). Progression-free survival was defined as the time from randomization to the time of the first documented disease progression or death, whichever occurred first. Disease progression was defined as ≥ 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since treatment started or the unequivocal progression of existing non-target lesions, or appearance of new lesion(s). | Baseline to the 15 Sep 2008 cut-off date (up to 2 years, 6 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With a Complete Response or a Partial Response | Responses were evaluated using the Response Evaluation Criteria in Solid Tumors. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. 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. | Baseline to the 15 Sep 2008 cut-off date (up to 2 years, 6 months) | 
| Duration of Response | Duration of response was defined as the time from the first documented complete response or partial response to disease progression or death. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. 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. Responses were evaluated using the Response Evaluation Criteria in Solid Tumors. | Baseline to the 15 September 2008 cut-off date (up to 2 years, 6 months) | 
| Time to Treatment Failure | Time to treatment failure was defined as time from randomization to the date of disease progression, death, or withdrawal of treatment due to an adverse event, withdrawal of informed consent, insufficient therapeutic response, refusal of treatment/failure to co-operate, or failure to return, whichever occurred first. | Baseline to the 15 September 2008 cut-off date (up to 2 years, 6 months) | 
| Overall Survival | Overall survival was defined as the time from randomization to death from any cause. | Baseline to the 15 Sep 2008 cut-off date (up to 2 years, 6 months) |