Phase I/II Combined Biological Therapy of Breast Cancer Using Monoclonal Antibodies Directed Against HER2/Neu Proto-Oncogene and Vascular Endothelial Growth Factor
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Breast Cancer
- Sponsor
- Translational Oncology Research International
- Enrollment
- 50
- Locations
- 18
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 10 years ago
Overview
Brief Summary
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
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.
Investigators
Eligibility Criteria
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
Outcomes
Primary Outcomes
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 Outcomes
- 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