A Randomized Phase II Study of Bevacizumab in Combination With Docetaxel in Locally Advanced Breast Cancer
- Determine the effect of bevacizumab and docetaxel on reduction of microvessel density
and induction of apoptosis of endothelial and tumor cells in patients with locally
advanced breast cancer.
- Determine the safety profile of this regimen in these patients.
- Compare the effect of docetaxel and bevacizumab, in terms of objective response,
stabilization of disease, and progression-free survival, in these patients.
OUTLINE: This is a randomized study. Patients are stratified according to disease stage.
Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive docetaxel IV over 1 hour once weekly on weeks 1-6 and
bevacizumab IV over 60 minutes once every 2 weeks on weeks 1-8.
- Arm II: Patients receive docetaxel as in arm I. Treatment in both arms repeats every 8
weeks for 2 courses in the absence of disease progression or unacceptable toxicity.
After the second course, patients with stable or responsive disease undergo modified radical
mastectomy or breast-conserving surgery. Three to six weeks after surgery, patients undergo
radiotherapy 5 days a week for 7 weeks.
Approximately 4 weeks after the completion of radiotherapy, patients receive doxorubicin IV
over 5 minutes and cyclophosphamide IV over 30-60 minutes on day 1. Treatment repeats every
21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients with estrogen and/or progesterone receptor-positive disease also receive oral
tamoxifen daily for 5 years beginning after the completion of chemotherapy. Post-menopausal
patients may receive oral anastrozole once daily for 5 years instead of tamoxifen.
Patients are followed at 3, 6, and 12 months, every 6 months for 4 years, and then annually
PROJECTED ACCRUAL: A total of 60 patients (30 per treatment arm) will be accrued for this
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
To evaluate the ability of bevacizumab and docetaxel to reduce microvessel density and induce apoptosis of endothelial and tumor cells.
The primary outcome measure is the difference in change in biologic parameters between the two arms. Tumor biopsies are required to perform pre- and post-treatment tumor microvessel density determination, apoptosis by TUNEL assay, proliferation markers by immunohistochemistry(e.g. PCNA, Ki-67), and expression of nuclear clusterin/XIP8.
weeks 8 and 17
Paula Silverman, MD
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
United States: Federal Government
|Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center||Cleveland, Ohio 44106-5065|
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