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

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the breast, with measurable or non-measurable locally recurrent or metastatic disease
• Signed Informed Consent Form
• Age >/= 18 years
• For women of childbearing potential, use of accepted and effective method of non-hormonal contraception
• ECOG performance status of 0 or 1
• Ability and capacity to comply with study and follow-up procedures
• For anthracycline cohort only: adequate left ventricular function at study entry, defined as an LVEF >/= 50% by either MUGA scan or ECHO.
• For subjects who have received recent radiation therapy: recovery prior to Day 0 from any significant (Grade >/= 3) acute toxicity

Exclusion Criteria:

• Unknown 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 VEGF pathway-targeted therapy
• Known brain or other CNS metastases
• Blood pressure of > 150/100 mm Hg
• Unstable angina
• New York Heart Association (NYHA) Grade II or greater 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 (> 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; PTT and/or either INR or 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)