Treatment of HER2-Positive Metastatic Breast Cancer With Herceptin and Bevacizumab (Antibodies Against HER2 and VEGF)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of combined treatment with trastuzumab (Herceptin) and bevacizumab (anti-VEGF antibody) in patients with HER2-positive metastatic breast cancer.

Detailed Description
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Based on preclinical experiments conducted in our laboratories, we hypothesize that the aggressive behavior of HER2-overexpressing breast cancers is due in part to increased angiogenesis resulting from HER2-induced increases in vascular endothelial growth factor (VEGF) expression. In vivo experiments suggest that combined blockade of the HER2 receptor and VEGF results in superior anti-tumor efficacy compared with either treatment alone. The current clinical trial, for which the phase I portion has been completed, will examine the efficacy and safety of trastuzumab (Herceptin) and bevacizumab (anti-VEGF antibody) in the treatment of HER2-overexpressing metastatic breast cancer.

Official Title
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Phase I/II Combined Biological Therapy of Breast Cancer Using Monoclonal Antibodies Directed Against HER2/Neu Proto-Oncogene and Vascular Endothelial Growth Factor

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: Bevacizumab (drug), Herceptin (drug)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Metastatic or relapsed locally advanced breast cancer HER2-positive by FISH No prior chemotherapy for metastatic disease ECOG performance status 0-2 Normal left ventricular ejection fraction Bidimensionally measurable disease Oxygen saturation > 90% on room air Exclusion Criteria: Other invasive malignancy within 5 years More than 3 different metastatic sites >50% liver involvement by metastasis Newly diagnosed untreated Stage IIIB breast cancer Prior chemotherapy for metastatic disease Clinically significant cardiovascular disease History or evidence of CNS disease Major surgery within 28 days prior to day 0 Current or recent use of parenteral anticoagulants WBC < 3,000/uL Platelet count < 75,000/uL Hemoglobin < 9.0 g/dL Total Bilirubin > 2.0 mg/dL AST or ALT > 5 time upper limit of normal for subjects with documented liver metastases; > 2.5 times upper limit of normal for subjects without evidence of liver metastases Proteinuria (> 1g protein/24 hours at baseline) Prior therapy with Herceptin or rhuMAb VEGF (bevacizumab)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Bevacizumab (drug), Herceptin (drug)|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To establish the maximum tolerated dose (MTD) or recommended phase II dose of rhuMAb VEGF (bevacizumab) administered intravenously every 14 days to patients with HER2-amplified relapsed or metastatic breast cancer receiving concomitant Herceptin therapy |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the clinical safety and toxicities of rhuMAb VEGF when administered in combination with Herceptin |  |  | 
| To characterize the pharmacokinetics of rhuMAb VEGF and Herceptin given in combination |  |  | 
| To evaluate the efficacy of rhuMAb VEGF plus Herceptin in terms of clinical activity when administered as an intravenous infusion, in patients with previously untreated metastatic or relapsed breast cancer |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic breast cancer, HER2, Trastuzumab, Herceptin, VEGF, Bevacizumab, Avastin