Safety Study of Bevacizumab to Treat Women With a History of Breast Cancer and Suffering From Upper Extremity Lymphedema
NCT ID: NCT00318513
Last Updated: 2006-05-10
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
UNKNOWN
Clinical Phase
PHASE1
Total Enrollment
35 participants
Study Classification
INTERVENTIONAL
Brief Summary
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The purpose of this study is to determine the safety and side effects of bevacizumab in subjects with lymphedema who will initially receive bevacizumab alone and then in combination with standard manual lymphatic drainage (MLD) and combined decongestive therapy (CDT). This study will help to determine the dose of bevacizumab to be used in future studies of subjects with lymphedema.
Detailed Description
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Lymphedema occurs with varying frequency in patients with cancer but approximately 10-15% of all breast cancer patients will develop lymphedema following breast cancer treatment. Lymphedema in breast cancer patients following axillary lymph node dissection is caused by the interruption of the axillary lymphatic system by surgery or radiation therapy, which causes an accumulation of fluid in the subcutaneous tissue of the arm, with decreased distensibility of tissue around the joints and increased weight of the extremity. The primary current therapy employed involves complete decongestive therapy (CDT) which encompasses the use of manual lymphatic drainage (MLD) and compression bandaging (CB) to the affected limb.
The specific contribution of the vascular system to the development of lymphedema is unclear. Vascular permeability is a complex process which is primarily controlled by the interaction of the ligand vascular endothelial growth factor (VEGF). As a result of the understanding of the biology of VEGF and the anecdotal appreciation of women with lymphedema who have noted improvement in their lymphedema while on VEGF inhibitor therapy, it is hypothesized that the reduction in vascular permeability resulting from the use of a VEGF inhibitor either alone or in conjunction with standard decongestive lymphedema therapy may significantly improve the outcome for patients with this post-operative complication.
Bevacizumab is a recombinant humanized monoclonal antibody directed against VEGF. Bevacizumab blocks the development of new blood vessels in cancer and it is approved by the FDA for the treatment of colon cancer in combination with chemotherapy. While bevacizumab has been administered to thousands of patients with cancer, there is only limited information about the use of bevacizumab in subjects without active cancer.
This study will evaluate the safety profile of escalating doses of bevacizumab administered intravenously alone for 4 weeks followed by 4 weeks of therapy in combination with manual lymph drainage (MLD) and compression bandaging (CB) to patients with moderate to severe unilateral upper extremity lymphedema due to prior breast cancer therapy.
The specific contribution of the vascular system to the development of lymphedema is unclear. Vascular permeability is a complex process which is primarily controlled by the interaction of the ligand vascular endothelial growth factor (VEGF). As a result of the understanding of the biology of VEGF and the anecdotal appreciation of women with lymphedema who have noted improvement in their lymphedema while on VEGF inhibitor therapy, it is hypothesized that the reduction in vascular permeability resulting from the use of a VEGF inhibitor either alone or in conjunction with standard decongestive lymphedema therapy may significantly improve the outcome for patients with this post-operative complication.
Bevacizumab is a recombinant humanized monoclonal antibody directed against VEGF. Bevacizumab blocks the development of new blood vessels in cancer and it is approved by the FDA for the treatment of colon cancer in combination with chemotherapy. While bevacizumab has been administered to thousands of patients with cancer, there is only limited information about the use of bevacizumab in subjects without active cancer.
This study will evaluate the safety profile of escalating doses of bevacizumab administered intravenously alone for 4 weeks followed by 4 weeks of therapy in combination with manual lymph drainage (MLD) and compression bandaging (CB) to patients with moderate to severe unilateral upper extremity lymphedema due to prior breast cancer therapy.
Conditions
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Lymphedema
Study Design
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Allocation Method
NON_RANDOMIZED
Intervention Model
SINGLE_GROUP
Primary Study Purpose
TREATMENT
Blinding Strategy
NONE
Interventions
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Bevacizumab
Intervention Type
DRUG
Eligibility Criteria
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Inclusion Criteria
* Women with a history of breast cancer status post (s/p) prior surgical resection (i.e., either lumpectomy and radiation, modified radical mastectomy or radical mastectomy) with lymphedema defined as a difference in limb volume of at least 500 ml by perometric assessment
* Lymphedema may be newly diagnosed or previously treated as long as it is Stage I (pitting) or II (fibrosis) at the time of study entry.
* No known evidence of recurrent or active metastatic breast cancer
* No prior chemotherapy within 6 months of study entry and has recovered to grade 1 or less from the toxicity of all prior chemotherapy or radiation therapy (with the exception of alopecia); ongoing anti-estrogen therapy for post-menopausal survivors is permissible.
* Normal end organ function defined as: serum creatinine \< 1.5 mg/dl or a calculated creatinine clearance \> 50 ml/min; SGOT and SGPT \< 2.5 X upper limit of normal (ULN); total bilirubin \< 1.5 X ULN; absolute neutrophil count (ANC) \> 1,500 cells/µl; hemoglobin \> 10 g/dl (without transfusions); platelet count \> 100,000/µl; serum albumin within normal limits (WNL).
* Lymphedema may be newly diagnosed or previously treated as long as it is Stage I (pitting) or II (fibrosis) at the time of study entry.
* No known evidence of recurrent or active metastatic breast cancer
* No prior chemotherapy within 6 months of study entry and has recovered to grade 1 or less from the toxicity of all prior chemotherapy or radiation therapy (with the exception of alopecia); ongoing anti-estrogen therapy for post-menopausal survivors is permissible.
* Normal end organ function defined as: serum creatinine \< 1.5 mg/dl or a calculated creatinine clearance \> 50 ml/min; SGOT and SGPT \< 2.5 X upper limit of normal (ULN); total bilirubin \< 1.5 X ULN; absolute neutrophil count (ANC) \> 1,500 cells/µl; hemoglobin \> 10 g/dl (without transfusions); platelet count \> 100,000/µl; serum albumin within normal limits (WNL).
Exclusion Criteria
* Stage III (lymphostatic elephantiasis) lymphedema
* Clinical evidence of bilateral lymphedema. Those patients who have undergone bilateral breast cancer surgery or prophylactic mastectomy on the non-cancerous breast will be excluded.
* Any prior history of deep venous thrombosis (DVT) or pulmonary embolus (with the exception of prior line-related thrombotic events) or myocardial infarction (MI), cerebrovascular accident (CVA) or any other arterial thromboembolic event (i.e., transient ischemic attack \[TIA\], reversible ischemic neurologic deficit \[RIND\], history of angina pectoris, clinically significant peripheral vascular disease with claudication, etc.)
* Patients with problems with wound healing (e.g., diabetic ulcers), gastrointestinal fistula
* Patients receiving therapeutic anti-coagulation including full dose aspirin or non-steroidal anti-inflammatory agents known to inhibit platelet function (low dose coumadin for port prophylaxis and low dose aspirin are allowed)
* Untreated hypertension with a baseline systolic blood pressure (SBP) of \> 150 mmHg or a diastolic blood pressure (DBP) \>100 mmHg will be excluded (stable treated hypertension with values less than those noted will be eligible).
* A history of infectious complications of the involved arm or those with any contraindication to MLD + CB \[e.g., congestive heart failure (CHF), DVT, acute or chronic renal failure\] will be excluded.
* Women with a history of CHF \[New York Heart Association (NYHA) Class II or greater\] will be excluded.
* Pregnant or breast-feeding
* Unwilling to use an appropriate form of barrier contraception for the duration of the study and for three months following the last dose of bevacizumab
* Those patients who are actively undergoing MLD and/or CB at the time of study entry and for up to 4 weeks prior to entry
* Unable to provide written informed consent or to comply with study procedures
* Baseline urine protein : creatinine ratio \> 1.0
* Known evidence of a bleeding diathesis or coagulopathy
* Clinical evidence of bilateral lymphedema. Those patients who have undergone bilateral breast cancer surgery or prophylactic mastectomy on the non-cancerous breast will be excluded.
* Any prior history of deep venous thrombosis (DVT) or pulmonary embolus (with the exception of prior line-related thrombotic events) or myocardial infarction (MI), cerebrovascular accident (CVA) or any other arterial thromboembolic event (i.e., transient ischemic attack \[TIA\], reversible ischemic neurologic deficit \[RIND\], history of angina pectoris, clinically significant peripheral vascular disease with claudication, etc.)
* Patients with problems with wound healing (e.g., diabetic ulcers), gastrointestinal fistula
* Patients receiving therapeutic anti-coagulation including full dose aspirin or non-steroidal anti-inflammatory agents known to inhibit platelet function (low dose coumadin for port prophylaxis and low dose aspirin are allowed)
* Untreated hypertension with a baseline systolic blood pressure (SBP) of \> 150 mmHg or a diastolic blood pressure (DBP) \>100 mmHg will be excluded (stable treated hypertension with values less than those noted will be eligible).
* A history of infectious complications of the involved arm or those with any contraindication to MLD + CB \[e.g., congestive heart failure (CHF), DVT, acute or chronic renal failure\] will be excluded.
* Women with a history of CHF \[New York Heart Association (NYHA) Class II or greater\] will be excluded.
* Pregnant or breast-feeding
* Unwilling to use an appropriate form of barrier contraception for the duration of the study and for three months following the last dose of bevacizumab
* Those patients who are actively undergoing MLD and/or CB at the time of study entry and for up to 4 weeks prior to entry
* Unable to provide written informed consent or to comply with study procedures
* Baseline urine protein : creatinine ratio \> 1.0
* Known evidence of a bleeding diathesis or coagulopathy
Minimum Eligible Age
0 Years
Eligible Sex
FEMALE
Accepts Healthy Volunteers
No
Sponsors
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Genentech, Inc.
INDUSTRY
Sponsor Role
collaborator
Premiere Oncology of Arizona
OTHER
Sponsor Role
lead
Principal Investigators
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Michael S Gordon, MD
Role: PRINCIPAL_INVESTIGATOR
Premiere Oncology of Arizona
Locations
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Premiere Oncology of Arizona
Scottsdale, Arizona, United States
Site Status
Countries
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United States
Central Contacts
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References
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Other Identifiers
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AVF3251s
Identifier Type: -
Identifier Source: org_study_id