A Pilot Study of VEGF Inhibition in Patients With Lymphedema Following Breast Cancer Treatment

Inclusion Criteria:

Have unilateral lymphedema of the ipsilateral arm attributed to prior surgical treatment or radiation therapy for breast cancer that is severe enough to warrant therapy in the opinion of the subject and treating physician.

All subjects must have greater than a 3 cm total difference in arm circumference between the affected and unaffected arm measured at five defined points:

each hand just distal to the thumb
each wrist at its narrowest point
each arm 30 cm proximal to the tip of the middle finger
each arm 40 cm proximal to the tip of the middle finger
each arm 50 cm proximal to the tip of the middle finger (if possible before the axilla is reached.)
Be at least 18 years of age

Have adequate organ function as specified below:

AST and ALT less than or equal to 2.0 times ULN
Total bilirubin less than or equal to 1.5 mg/dL
Serum creatinine less than or equal to 1.5 mg/dL
Urine protein:creatinine ratio < 1.0*
LVEF > institutional limits of normal by MUGA or ECHO
PT INR < 1.5; PTT < 1.5 x normal
Absolute neutrophil count greater than or equal to 1000/mm3
Platelets greater than or equal to 100,000/mm3
Agree to use effective contraceptive methods during the course of the study if the subject has child-producing potential
Have an ECOG performance status of 0 or 1

Exclusion Criteria:

Subjects must not be pregnant, lactating, or refuse to use appropriate birth control
Subjects must not have an active infection requiring parenteral or oral antibiotics

Subjects must not have clinically significant cardiovascular or cerebrovascular disease, including:

Any history of:

Cerebrovascular disease including TIA, stroke or subarachnoid hemorrhage
Ischemic bowel
Hypertensive crisis or hypertensive encephalopathy Within the last 12 months
Myocardial infarction
Unstable angina
New York Heart Association (NYHA) grade II or greater congestive heart failure
Grade II or greater peripheral vascular disease
DVT or PE Active at study entry
Uncontrolled hypertension defined as SBP > 150 or DBP > 100
Uncontrolled or clinically significant arrhythmia.
Subjects may not have locally recurrent or metastatic disease
Subjects may not require concurrent therapeutic anticoagulation. (NOTE: Prophylactic doses of coumadin to maintain patency of a vascular access device is allowed). In addition, subjects with a bleeding diathesis are excluded.
Subjects may not have had major surgery within 4 weeks of starting protocol therapy (NOTE: Placement of a vascular access device is not considered major surgery)
Subjects may not have received radiation therapy, chemotherapy or trastuzumab within the past 6 weeks (NOTE: Concurrent adjuvant hormonal therapy is allowed.)
Subjects may not have altered the physical therapy regimen for lymphedema within the past month
Subjects may not have an indwelling venous device in the ipsilateral arm
Subjects may not have bilateral lymphedema
Subjects may not have a non-healing wound, ulcer or bone fracture.
Subjects may not have a known hypersensitivity to any component of Bevacizumab