Safety Study of Bevacizumab to Treat Women With a History of Breast Cancer and Suffering From Upper Extremity Lymphedema

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2006 by Premiere Oncology of Arizona.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
Genentech
Information provided by:
Premiere Oncology of Arizona
ClinicalTrials.gov Identifier:
NCT00318513
First received: April 24, 2006
Last updated: May 9, 2006
Last verified: April 2006
  Purpose

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.


Condition Intervention Phase
Lymphedema
Drug: Bevacizumab
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study Evaluating the Safety of Bevacizumab in Women With a History of Breast Cancer Suffering From Moderate to Severe Upper Extremity Lymphedema

Resource links provided by NLM:


Further study details as provided by Premiere Oncology of Arizona:

Estimated Enrollment: 35
Detailed Description:

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.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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).

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00318513

Contacts
Contact: Michael S Gordon, MD 480-860-5000 mgordon@premiereoncology.com

Locations
United States, Arizona
Premiere Oncology of Arizona Not yet recruiting
Scottsdale, Arizona, United States, 85260
Principal Investigator: Michael S Gordon, MD         
Sponsors and Collaborators
Premiere Oncology of Arizona
Genentech
Investigators
Principal Investigator: Michael S Gordon, MD Premiere Oncology of Arizona
  More Information

Publications:

ClinicalTrials.gov Identifier: NCT00318513     History of Changes
Other Study ID Numbers: AVF3251s
Study First Received: April 24, 2006
Last Updated: May 9, 2006
Health Authority: United States: Food and Drug Administration

Keywords provided by Premiere Oncology of Arizona:
breast cancer
lymphedema
extremity
women

Additional relevant MeSH terms:
Lymphedema
Breast Neoplasms
Stress, Psychological
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Lymphatic Diseases
Behavioral Symptoms
Bevacizumab
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on August 19, 2014