A Study Evaluating the Efficacy and Safety of Bevacizumab in Combination With Chemotherapy in Untreated Metastatic Breast Cancer (RIBBON 1)

Exclusion Criteria

• •Unknown human epidermal growth factor receptor 2 (HER2) status or known HER2-positive status.
• •Prior chemotherapy for locally recurrent or metastatic disease.
• •Prior hormonal therapy less than 1 week prior to Day 0.
• •Prior adjuvant or neoadjuvant chemotherapy within 12 months prior to Day 0.
• •For anthracycline cohort only: Prior anthracycline as part of neoadjuvant or adjuvant therapy for localized breast cancer.
• •Investigational therapy within 28 days of Day 0.
• •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study.
• •Minor surgical procedures, such as fine needle aspirations or core biopsies, within 7 days prior to Day 0.
• •Prior therapy with bevacizumab, sorafenib, sunitinib, or other vascular endothelial growth factor (VEGF) pathway-targeted therapy.
• •Known brain or other central nervous system (CNS) metastases.
• •Blood pressure of \> 150/100 mmHg.
• •Unstable angina.
• •New York Heart Association (NYHA) Grade II or greater congestive heart failure (CHF).
• •History of myocardial infarction within 6 months prior to Day 0.
• •History of stroke or transient ischemic attack within 6 months prior to Day 0.
• •Clinically significant peripheral vascular disease.
• •Evidence of bleeding diathesis or coagulopathy.
• •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0.
• •Serious non-healing wound, ulcer, or bone fracture.
• •Pregnancy (positive serum pregnancy test) or lactation.
• •Inadequate organ function, as evidenced by any of the following laboratory values: Absolute neutrophil count \< 1500/uL; platelet count \< 100,000/uL; total bilirubin \> 1.5 mg/dL; alkaline phosphatase, AST, and/or ALT \> 2x upper limit of normal (ULN) (\> 5x ULN in subjects with known liver or, for alkaline phosphatase elevations, bone involvement); alkaline phosphatase \> 2x ULN (\> 7x ULN in subjects with known bone involvement); serum creatinine \> 2.0 mg/dL; partial thromboplastin time (PTT) and/or either international normalized ratio (INR) or prothrombin time (PT) \> 1.5x upper limit of normal (except for subjects receiving anti-coagulation therapy); urine protein/creatinine ratio \> 1.0 at screening for U.S. subjects, or urine dipstick for proteinuria \>/= 1+ at screening followed by 24-hour urine collection demonstrating \> 1 g protein/24 hr for ex-U.S. subjects.
• •Uncontrolled serious medical or psychiatric illness.
• •Active infection requiring intravenous (iv) antibiotics at Day 0.
• •History of other malignancies within 5 years of Day 0 except for tumors with a negligible risk for metastasis or death, such as adequately controlled basal cell carcinoma or squamous-cell carcinoma of the skin or carcinoma in situ of the cervix (subjects with a history of bilateral breast cancer will be eligible).