| Exclusion Criteria: | 1) Prior therapy with two or more regimens for metastatic breast cancer
2) Any systemic anti-cancer therapy within 3 weeks prior to Day 1 of cycle 1
3) Major surgical procedure (except CNS surgery), open biopsy, or significant traumatic injury within 30 days prior to day 1 of cycle 1, or anticipation of need for major surgical procedure during the course of the study
4) Minor surgical procedure, such as fine-needle aspiration or core biopsy, within 7 days prior to Day 1 of Cycle 1
5) Prior therapy with a taxane for metastatic breast cancer
6) Prior therapy with bevacizumab, sorafenib, sunitinib, or other putative VEGF pathway-targeted therapy following diagnosis of breast cancer
7) Prior exposure to experimental treatment targeting either the HGF or MET pathway
8) Prior therapy with hormones and/or trastuzumab
9) Bevacizumab Exclusion Criteria: Known Brain or other CNS metastases, except for treated brain metastasis as defined below: A head computed tomography (CT) scan or magnetic resonance imaging (MRI) scan must be performed within 6 weeks prior to Day 1 of Cycle 1 to confirm the absence of CNS metastases. Treated brain metastases are defined as having no evidence of progression or hemorrhage for a minimum period of 4 weeks following treatment, and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy, radiosurgery (Gamma Knife, linear accelerator, or equivalent), or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 of Cycle 1 will be excluded.
10) Uncontrolled hypertension defined by systolic pressure >150 mmHg and/or diastolic pressure >100 mmHg, with or without anti-hypertensive medication. Patients with initial blood pressure elevations are eligible if initiation or adjustment of anti-hypertensive medication lowers blood pressure to meet entry criteria.
11) Unstable angina
12) History of hypertensive crisis or hypertensive encephalopathy
13) New York Heart Association Grade >/=II congestive heart failure
14) History of myocardial infarction within 6 months prior to Day 1 of Cycle 1
15) History of stroke or transient ischemic attack within 6 months prior to Day 1of Cycle 1
16) Clinically significant peripheral vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to Day 1 of Cycle 1
17) Evidence of bleeding diathesis or coagulopathy
18) History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 1 of Cycle 1
19) History of anaphylactic reaction to monoclonal antibody therapy not controlled with pre-medication
20) History of hemoptysis (>/=1/2 teaspoon of bright red blood per episode) within 1 month prior to Day 1 of Cycle 1
21) Known hypersensitivity to any component of bevacizumab
22) Serious non-healing wound, active ulcer, or untreated bone fracture. Fractures secondary to metastatic disease may be allowed if stable and if surgery (if applicable) is completed >/= 30 days prior to Day 1 of Cycle 1.
23) Pregnancy (positive serum pregnancy test) or lactation
24) 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, AST or ALT >2 times the upper limit of normal (ULN), or > 5 ULN in patients with known liver involvement, Alkaline phosphatase >2 ULN, or > 5 ULN in patients with known liver involvement and >7 ULN in patients with known bone involvement, Serum creatinine >2.0 mg/dL, PTT, INR, or PT > 1.5 ULN (except for patients receiving anticoagulation therapy), Urine dipstick or urinalysis for proteinuria >/=1+ at screening followed by 24-hour urine collection demonstrating > 1g protein
25) Uncontrolled serious medical or psychiatric illness
26) Active infection requiring IV antibiotics at Day 1 of Cycle 1
27) History of other malignancies within 5 years prior to Day 1 of Cycle 1, 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, Patients with a history of bilateral breast cancer or previous history of breast cancer will be eligible.
28) QTc interval at screening >470 msec (average of triplicate screening measurements)
29) ECG waveform morphology at screening incompatible with ECG interval measurement by the central laboratory |