Phase II Trial of Fulvestrant and Bevacizumab in Patients With Metastatic Breast Cancer Previously Treated With an Aromatase Inhibitor

Inclusion Criteria

DISEASE CHARACTERISTICS:

- Histologically or cytologically confirmed breast cancer

- Metastatic disease

- Must have received an aromatase inhibitor (e.g., letrozole, anastrozole, or
exemestane) in an adjuvant or metastatic setting

- If tumor is HER2 positive (3+ by immunohistochemistry or amplified by fluorescent in
situ hybridization) the patient must have received ≥ 1 prior trastuzumab
(Herceptin®)-containing regimen unless there is a contraindication to trastuzumab

- Measurable or nonmeasurable disease, including any of the following :

- Bone metastasis

- Pleural/pericardial effusion

- Ascites

- Inflammatory skin changes

- No microscopic residual disease only

- Enrolled on or refused enrollment on clinical trial NCCTG-N0392

- No evidence of active brain metastasis including leptomeningeal involvement

- CNS metastasis controlled (i.e., at least 2 months of no symptoms or evidence of
progression) by prior surgery and/or raditherapy are allowed

- Hormone receptor status:

- Estrogen and/or progesterone receptor-positive tumor

PATIENT CHARACTERISTICS:

- Male or female

- Female patients must be post-menopausal based on any 1 of the following criteria:

- Age ≥ 60 years

- Age ≥ 45 years with last menstrual period ≥ 12 months prior to study entry

- Estradiol and follicle-stimulating hormone levels in postmenopausal range

- History of bilateral oophorectomy

- ECOG performance status 0-2

- Life expectancy > 3 months

- Fertile patients must use effective contraception during and for 30 days after
completion of study treatment

- WBC ≥ 3,000 mg/dL

- Hemoglobin > 8 g/dL

- Absolute neutrophil count > 1,000/mm³

- Platelet count ≥ 100,000/mm³

- Bilirubin ≤ 1.5 times upper limit of normal (ULN)

- Alkaline phosphatase ≤ 2.5 times ULN

- AST and ALT ≤ 2.5 times ULN

- Creatinine ≤ 1.5 times ULN

- Urine protein < 1+ OR < 1 g of protein by 24-hour urine collection

- No nephrotic syndrome

- No uncontrolled hypertension (i.e., blood pressure [BP] > 160/90 mm Hg on ≥ 2
occasions at least 5 minutes apart)

- Patients who have recently started or adjusted antihypertensive medications are
eligible provided BP is < 140/90 mm Hg on any new regimen for ≥ 3 different
observations in ≥ 14 days

- No clinically significant cardiac disease, including any of the following:

- Congestive heart failure

- Symptomatic coronary artery disease

- Unstable angina

- Cardiac arrhythmias not well controlled with medication

- Myocardial infarction within the past 12 months

- No arterial or venous thrombosis within the past 12 months

- No hemoptysis or gastrointestinal hemorrhage within the past 6 months

- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within
the past 4 weeks

- No significant traumatic injury within the past 4 weeks

- No active, unresolved infection

- No history of hypertensive crisis or hypertensive encephalopathy

- No history of bleeding diathesis or uncontrolled coagulopathy

- No history of cerebrovascular accident, hemorrhage, or stroke

- No allergy or hypersensitivity to drug product excipients, murine antibodies, or
agents chemically similar to study drugs

- No other malignancy within the past 3 years except for basal cell or squamous cell
skin cancer or carcinoma in situ of the cervix

- No other serious medical condition that would preclude study therapy or compliance

PRIOR CONCURRENT THERAPY:

- See Disease Characteristics

- Prior radiotherapy to a target lesion allowed provided there has been clear
progression since radiotherapy was completed

- At least 4 weeks since prior radiotherapy

- Single-dose radiation for palliation or to a nontarget lesion only allowed
within the past 4 weeks

- No more than 1 prior chemotherapy regimen for metastatic disease

- No more than 2 prior endocrine (hormonal) therapy regimens in the neoadjuvant,
adjuvant, or metastatic setting

- At least 4 weeks since prior major surgery or open biopsy

- At least 4 weeks since prior chemotherapy or immunologic therapy

- At least 2 weeks since prior and no concurrent use of any of the following agents:

- Aspirin (daily low-dose [81 mg] aspirin allowed])

- Thrombolytic agents

- Anticoagulants (low-dose anticoagulation therapy to maintain patency of a
vascular access device is allowed)

- No concurrent treatment in another clinical study with investigational procedures or
investigational therapies

- No other concurrent anticancer therapy, including chemotherapy, biologic agents, or
radiotherapy

- No routine use of granulocyte colony-stimulating factors during course 1

- No concurrent oprelvekin