A Pilot Study to Evaluate Angiogenesis After Treatment With Bevacizumab (Anti-VEGF Humanized Monoclonal Antibody) in Previously Untreated Patients With Inflammatory Breast Cancer or Locally Advanced Breast Cancer
This is a pilot study in patients with previously untreated inflammatory breast cancer (IBC)
or locally advanced breast cancer (LABC) to evaluate angiogenesis parameters after treatment
with rhuMAb VEGF - recombinant humanized monoclonal antibody vascular endothelial growth
factor (bevacizumab). The challenge for new molecular-targeted anti-angiogenesis therapy is
to devise appropriate and reliable markers to monitor efficacy. This may be achieved
directly by evaluating changes in angiogenesis parameters in tumor samples. The use of less
invasive surrogate markers to assess the efficacy of anti-angiogenic therapy is preferable.
This may include functional changes in tumor vasculature assessed using non-invasive methods
such as magnetic resonance imaging (MRI) or determination of changes in circulating soluble
markers of angiogenesis.
Most breast cancers over express VEGF thus making it an ideal disease for treatment with
anti-angiogenesis therapy. This study will evaluate the effects of bevacizumab on
angiogenesis parameters both molecular and functional. The first cycle will consist of
bevacizumab alone followed by six cycles of bevacizumab in combination with doxorubicin and
docetaxel (AT). Loco-regional therapy will follow and bevacizumab will be recommenced for
Changes in pre-designated angiogenesis parameters will be assessed at baseline, three weeks
after bevacizumab and after three cycles of AT/bevacizumab. The first three molecular
parameters: endothelial cell proliferation, endothelial cell apoptosis and tissue VEGF
require multiple tumor core biopsies obtained using a mammotome. The fourth parameter
k(ep), the redistribution constant is obtained using dynamic MRI. To determine the
variability of the values of the three molecular primary angiogenesis parameters, multiple
biopsies will be sampled at the same time points. An attempt will be made to correlate each
of the four primary angiogenesis parameters with time to progression/recurrence. The
effects of bevacizumab alone and AT/bevacizumab directly on tumor vasculature using dynamic
MRI imaging and on the circulating angiogenesis marker, serum vascular cell adhesion
molecule-1 (VCAM-1) at the same three time points and prior to surgery and will be
undertaken in an exploratory manner. An attempt will be made to correlate changes in these
parameters with clinical findings and changes in tissue angiogenesis parameters.
Additionally, other angiogenesis biomarkers will also be studied in an exploratory manner.
Thrombosis factors will be monitored given the increased incidence of venous and arterial
thrombosis seen in previous clinical trials using bevacizumab. An increase in the incidence
of hypertension has also been seen. A subset of patients in this study will undergo
frequent blood pressure monitoring to obtain a profile of the effect of bevacizumab on blood
Primary Purpose: Treatment
To determine in IBC or LABC whether a change in any of the 4 angiogenesis parameters; 3 primary molecular parameters or the dynamic MRI parameter can be detected from baseline to 3 wks after treatment with bevacizumab.
Suparna Wedam, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|