Phase I Study Evaluating the Safety of Bevacizumab in Women With a History of Breast Cancer Suffering From Moderate to Severe Upper Extremity Lymphedema

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