A Pilot Study of Bevacizumab With Dose Dense Doxorubicin and Cyclophosphamide (AC) Followed by Dose Dense Nanoparticle Albumin Bound Paclitaxel for the Treatment of Early Stage Breast Cancer
- Determine the cardiac safety of adjuvant concurrent bevacizumab and dose-dense
doxorubicin hydrochloride and cyclophosphamide followed by dose-dense paclitaxel
albumin-stabilized nanoparticle formulation and maintenance therapy comprising
bevacizumab alone in patients with early-stage breast cancer.
- Determine the noncardiac toxicity of this regimen in these patients.
- Determine the efficacy of this regimen, in terms of time to tumor recurrence and
overall survival, in these patients.
- Explore changes in circulating endothelial cells and circulating tumor cells from
pre-treatment levels in patients with no evidence of disease.
- Prospectively explore the use of serial troponin I as a predictor of cardiac toxicity
in patients treated with this regimen.
- Prospectively explore the relationship between plasma renin activity and hypertension
in patients treated with bevacizumab and chemotherapy.
OUTLINE: This is a nonrandomized, pilot, multicenter study.
Patients receive doxorubicin hydrochloride IV, cyclophophamide IV, and bevacizumab IV over
30-90 minutes on day 1 and pegfilgrastim subcutaneously (SC) on day 2. Treatment repeats
every 2 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.
Patients then receive paclitaxel albumin-stabilized nanoparticle formulation IV over 30
minutes on day 1 and pegfilgrastim SC on day 2. Treatment with paclitaxel albumin-stabilized
nanoparticle formulation and pegfilgrastim repeats every 2 weeks for 4 courses in the
absence of disease progression or unacceptable toxicity. Patients then receive maintenance
therapy comprising bevacizumab IV over 30-90 minutes on day 1. Treatment with maintenance
therapy repeats every 3 weeks for 12 courses in the absence of disease progression or
Blood samples are collected at baseline and periodically during study treatment. Samples are
analyzed for circulating endothelial cells (by flow cytomery [FC]), circulating epithelial
cells (by immunocytochemistry and FC), troponin I concentrations (by enzyme immunoassay or
chemiluminescent microparticle immunoassay), and plasma renin activity (by
After completion of study treatment, patients are followed every 4-6 months for 3 years,
every 6 months for 2 years, and then annually thereafter.
PROJECTED ACCRUAL: A total of 75 patients will be accrued for this study.
Allocation: Non-Randomized, Primary Purpose: Treatment
Maura N. Dickler, MD
Memorial Sloan-Kettering Cancer Center
United States: Federal Government
|Memorial Sloan-Kettering Cancer Center||New York, New York 10021|