Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00016549
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2001-05-16
Brief Title:
Bevacizumab to Treat Inflammatory Breast Cancer or Locally Advanced Breast Cancer
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2012-04-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 andor 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 hearts pumping ability or echocardiogram ultrasound scan of the heart to evaluate heart function
Blood pressure monitoring
Urine tests
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
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 andor 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 hearts pumping ability or echocardiogram ultrasound scan of the heart to evaluate heart function
Blood pressure monitoring
Urine tests
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
Detailed Description:
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 ATbevacizumab 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 kep 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 progressionrecurrence The effects of bevacizumab alone and ATbevacizumab 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
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 ATbevacizumab 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 kep 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 progressionrecurrence The effects of bevacizumab alone and ATbevacizumab 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-C-0173 | None | None | None |