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