Bevacizumab Plus Vinorelbine in Treating Patients With Stage IV Breast Cancer

Inclusion Criteria:

Histologically or cytologically confirmed stage IV breast cancer

Patients without pathologic or cytologic confirmation of metastatic disease must have unequivocal evidence of metastasis by physical exam or radiologic study

Must meet 1 of the following criteria:

Received 1 or 2 prior conventional chemotherapy regimens for metastatic disease
Relapsed within 1 year after adjuvant chemotherapy and no prior chemotherapy for metastatic disease

At least 1 unidimensionally measurable lesion, meeting 1 of the following criteria:

At least 20 mm by conventional techniques
At least 10 mm by spiral CT scan
No CNS metastases by CT scan or MRI within the past 6 weeks
No prior or concurrent primary CNS tumor on physical exam
Disease progression after bone marrow or peripheral blood stem cell transplantation allowed
HER2-positive tumors allowed if previously treated with trastuzumab (Herceptin)

Hormone receptor status:

Not specified
Male or female
Performance status - ECOG 0-2
Performance status - Karnofsky 60-100%
More than 3 months
Absolute neutrophil count at least 1,500/mm^3
Hemoglobin at least 9 g/dL
Platelet count at least 100,000/mm^3
No prior bleeding diathesis or coagulopathy
Bilirubin no greater than 1.5 times upper limit of normal (ULN)
AST/ALT no greater than 2.5 times ULN
INR no greater than 1.5
Creatinine less than 2 mg/dL
Urine protein no greater than +1 by dipstick
Urine protein less than 500 mg by 24-hour urine collection
LVEF at least 50%
No prior stroke
No New York Heart Association class II-IV congestive heart failure
No serious cardiac arrhythmia requiring medication, including atrial fibrillation requiring systemic anticoagulation
No grade II or greater peripheral vascular disease within the past year
No clinically significant peripheral artery disease
No deep vein thrombosis or embolism within the past 5 years

No arterial thromboembolic event within the past 6 months, including any of the following:

Transient ischemic attack
Cerebrovascular accident
Unstable angina
Myocardial infarction
No other significant cardiovascular disease
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No evidence of seizures not controlled with standard medical therapy
No prior allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab or other agents used in the study
Prior mild infusion reaction to trastuzumab allowed
No serious non-healing wound, ulcer, or bone fracture
No significant traumatic injury within the past 4 weeks
No other concurrent illness (such as active infection) that would require active treatment or preclude study
No psychiatric illness or social situation that would preclude study
See Disease Characteristics
No prior bevacizumab
No other prior experimental angiogenesis inhibitors
At least 2 weeks since prior trastuzumab and recovered
Concurrent epoetin alfa or filgrastim (G-CSF) allowed
See Disease Characteristics
At least 2 weeks since prior chemotherapy and recovered
No prior vinorelbine
No more than 2 prior conventional chemotherapy regimens for metastatic breast cancer
Prior hormonal therapy allowed
At least 1 week since prior radiotherapy and recovered
No concurrent radiotherapy
At least 4 weeks since prior major surgical procedure or open biopsy
At least 1 week since prior fine-needle aspiration except in the breast
No concurrent major surgical procedure
Recovered from the toxic effects of any prior therapy
At least 10 days since prior oral or parenteral anticoagulants (e.g., heparin or warfarin) except to maintain the patency of permanent, indwelling central venous catheter
At least 10 days since prior thrombolytic agents
No chronic aspirin therapy greater than 325 mg per day or non-steroidal anti-inflammatory medications that inhibit platelet function
No concurrent COX-2 inhibitors that inhibit platelet function
No other concurrent investigational or commercial agents or therapies for the malignancy
No concurrent antiretroviral therapy for HIV-positive patients
No concurrent ketoconazole, zidovudine, or macrolide antibiotics
No concurrent oral or parenteral anticoagulants except to maintain patency of permanent, indwelling central venous catheter
No concurrent thrombolytic agent
Concurrent bisphosphonates allowed
Concurrent celecoxib or rofecoxib allowed