Bevacizumab to Treat Inflammatory Breast Cancer or Locally Advanced Breast Cancer
|ClinicalTrials.gov Identifier: NCT00016549|
Recruitment Status : Completed
First Posted : May 17, 2001
Last Update Posted : July 2, 2017
This study will evaluate the effectiveness of the drug bevacizumab, in combination with doxorubicin and docetaxel, in improving survival of patients with inflammatory breast cancer or locally advanced breast cancer. Inflammatory breast cancer is an aggressive form of locally advanced breast cancer that often causes a red, swollen, tender breast and is associated with a poor prognosis. Bevacizumab blocks the growth of new blood vessels that supply oxygen and nutrients to tumors, and therefore, may kill cancer cells or stop their growth. Doxorubicin and docetaxel are approved drugs for treating breast cancer.
Patients 18 years of age or older with stage inflammatory breast cancer who have not been treated with chemotherapy or radiation therapy may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, chest x-ray, electrocardiogram, and MUGA scan or echocardiography (see below). A mammogram of both breasts, dynamic MRI imaging of the affected breast, computed tomography (CT) of the head, chest, abdomen and pelvis, and a bone scan are done to determine the extent of disease.
Participants undergo the following procedures at various intervals before, during and/or after completing chemotherapy:
Tumor and skin biopsies to study the effects of bevacizumab on tumor blood vessels, tumor growth, and the biology of inflammatory breast cancer. A small piece of tumor tissue and a small piece of skin from the affected breast are removed under local anesthesia for microscopic study.
Dynamic MRI to examine changes in the blood vessels and breast cancer following bevacizumab treatment. This test involves injecting a contrast liquid into a vein before scanning. A standard MRI scan is done before the dynamic MRI.
Blood tests are done to 1) study clot formation and breakdown, 2) measure levels of VEGF (a substance produced by breast cancer cells) and VCAM-1 (a substance produced by cells lining blood vessel walls), and 3) check blood counts and liver and kidney function.
MUGA (a nuclear medicine scan that checks the heart's pumping ability) or echocardiogram (ultrasound scan of the heart to evaluate heart function.
Blood pressure monitoring
CT scans and x-rays to evaluate disease before and after treatment.
Patients will have a central venous line (plastic tube) placed into a major vein in the chest before beginning treatment. The line stays in the body during the entire treatment period and is used to give chemotherapy and other medications, if needed, and to draw blood samples. All treatment is given on a single day every 3 weeks. This constitutes one treatment cycle. Cycle 1 consists of bevacizumab alone; cycles 2 through 7 consist of bevacizumab with doxorubicin and docetaxel. During each cycle, patients also receive injections under the skin of G-CSF, a drug that raises the number of infection-fighting white blood cells, which are often decreased as a side effect of chemotherapy. After cycle 7, patients may require surgery and radiation or radiation alone. After radiation treatment, bevacizumab is re-started, given alone every 3 weeks for an additional eight cycles. Patients whose tumors are positive for estrogen or progesterone receptors will be advised to take the drug tamoxifen or anastrozole for 5 years to decrease the chances of disease recurrence. This would begin with cycle 8.
|Condition or disease||Intervention/treatment||Phase|
|Breast Cancer||Biological: Bevacizumab||Phase 2|
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 eight cycles.
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 pressure.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||21 participants|
|Official Title:||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|
|Study Start Date :||May 13, 2001|
|Primary Completion Date :||January 29, 2007|
|Study Completion Date :||January 29, 2007|
U.S. FDA Resources
- 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.
- To attempt to correlate each of the four primary parameters with clinical findings and time to progression/recurrence.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00016549
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Suparna Wedam, M.D.||National Cancer Institute (NCI)|