VEGF Trap in Treating Patients With Metastatic Breast Cancer

Inclusion Criteria:

Histologically or cytologically confirmed adenocarcinoma of the breast

Clinical evidence of metastatic disease

No more than 2 prior chemotherapy regimens for metastatic disease

Prior neoadjuvant or adjuvant chemotherapy allowed*
At least 1 prior regimen (in any setting) must have included a taxane and/or an anthracycline

Measurable disease, defined as ≥ 1 lesion whose longest diameter can be accurately measured per RECIST criteria

No nonmeasurable disease, defined as all other lesions, including small lesions(longest diameter < 20 mm) and truly nonmeasurable lesions, including the following:

Bone lesions
Leptomeningeal disease
Ascites
Pleural/pericardial effusion
Inflammatory breast disease
Lymphangitis cutis/pulmonis
Abdominal masses that are not confirmed and followed by imaging techniques
Cystic lesions
Patients with HER2-positive tumors (3+ by immunohistochemistry or amplified by fluorescent in situ hybridization [FISH]) must have received ≥ 1 prior trastuzumab (Herceptin®)-containing regimen in either the adjuvant or metastatic setting, unless there was a contraindication
No known CNS metastases
No evidence of leptomeningeal involvement
Hormone receptor status not specified
Male or female
Menopausal status not specified
ECOG performance status 0-1
Life expectancy > 3 months
WBC ≥ 3,000/mm³
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 75,000/mm³
Hemoglobin > 8.0 g/dL
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Alkaline phosphatase ≤ 3 times ULN
AST and ALT ≤ 2.5 times ULN
Creatinine ≤ 1.5 times ULN
Urine protein:creatinine ratio < 1 OR urine protein < 500 mg by 24-hour urine collection
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 6 months after completion of study treatment
No significant traumatic injury within the past 4 weeks
No history of allergy or hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies, drug product excipients, or agents chemically or biologically similar to VEGF Trap
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
No nonhealing wound, fracture, or ulcer
No stage III or IV invasive, nonbreast malignancy within the past 5 years
No history of lung carcinoma of squamous cell type

No clinically significant cardiovascular disease, including any of the following:

Cerebrovascular accident or stroke within the past 6 months
Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg OR systolic BP > 180 mm Hg if diastolic blood pressure < 90 mm Hg on ≥ 2 separate occasions within the past 3 months
Myocardial infarction, coronary artery bypass graft, or unstable angina within the past 6 months
New York Heart Association class III or IV cardiovascular disease
Serious cardiac arrhythmia requiring medication
Peripheral vascular disease ≥ grade 2 within the past 6 months
Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months
No evidence of bleeding diathesis or uncontrolled coagulopathy
No active, unresolved infection
No serious concurrent medical condition that would preclude study participation
No other condition or circumstance that would preclude compliance with study requirements
See Disease Characteristics
Prior hormonal therapy in the neoadjuvant, adjuvant, or metastatic setting allowed
No prior bevacizumab
More than 4 weeks since prior chemotherapy, endocrine therapy, experimental drug therapy, or immunotherapy and recovered
More than 4 weeks since prior major surgery or open biopsy
More than 7 days since prior core biopsy

More than 2 weeks since prior radiotherapy, except if to a nontarget lesion only

Prior radiotherapy to a target lesion allowed only if there has been clear progression of the lesion since radiotherapy was completed
Prior single-dose palliative radiotherapy within the past 2 weeks allowed
No concurrent major surgery
No concurrent trastuzumab

Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed provided the following criteria are met:

INR in-range (usually between 2 and 3) on a stable dose of oral anticoagulant or on a stable dose of low molecular weight heparin
No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
No concurrent combination antiretroviral therapy for HIV-positive patients
No concurrent participation in another investigational clinical trial
No other concurrent chemotherapeutic agents, endocrine therapy, biologic agents, radiotherapy, or other nonprotocol antitumor therapy