RATIONALE: Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bavituximab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving paclitaxel together with bavituximab may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects of giving paclitaxel and bavituximab together in treating patients with Human Epidermal growth factor Receptor 2 (HER2 )-negative metastatic breast cancer

PRIMARY OBJECTIVES:

I. To determine the safety, feasibility, and tolerability of combining paclitaxel with weekly bavituximab therapy.

SECONDARY OBJECTIVES:

I. To describe changes in pharmacodynamic markers and coagulation markers in response to single agent and combined therapy.

OUTLINE:

Patients receive paclitaxel intravenously (IV) on days 1, 8, and 15 and bavituximab IV on days 1, 8, 15, and 22 (days 15 and 22 only of course 1). Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Inclusion Criteria:

• Written informed consent has been obtained
• Life expectancy of at least 3 months
• Histologically or cytologically confirmed, Her-2 negative breast cancer with evidence of metastatic disease
• Measurable or evaluable disease by Response Evaluation Criteria In Solid Tumors (RECIST)
• Eastern Cooperative Oncology Group (ECOG) Performance Status =< 2
• Adequate hematologic function (absolute neutrophil count [ANC] >= 1,500 cells/uL; hemoglobin >= 9 g/dL; platelets >= 100,000/uL and =< 500,000/uL)
• Adequate renal function (serum creatinine =< 1.5 mg/dL or calculated creatinine clearance >= 60 ml/min)
• Adequate hepatic function (total or direct bilirubin =< Upper Limit of Normal (ULN), Alk Phos =< 4 x ULN)
• Prothrombin time international normalized ratio within institutional normal limits
• Activated partial thromboplastin time =< 1.5 x ULN
• New York Heart Association classification I or II
• Female patients must have a negative urine pregnancy test at prestudy (not applicable to patients with bilateral oophorectomy and/or hysterectomy or to those patients who are postmenopausal)

Exclusion Criteria:

• Known history of bleeding diathesis or coagulopathy (e.g., von Willebrand Disease, Hemophilia)
• Any current evidence of clinically significant active bleeding
• Any history of significant thromboembolic events (i.e., deep vein thrombosis or pulmonary thromboembolism) within the last five years or requirement for ongoing therapy with oral or parenteral anticoagulants; central venous catheter-related thrombosis > 12 months ago and low dose anticoagulants to maintain patency of lines are allowed; patients taking anticoagulants (e.g., prophylactic heparin or enoxaparin) are required to observe the washout period of 1 week prior to study drug infusion on Study Day 1
• Concurrent hormone therapy (i.e., estrogen contraceptives, hormone replacement, anti-estrogen); patients taking concurrent hormone therapy are required to observe the washout period of 2 weeks prior to study drug infusion on Study Day 1
• Grade 2 or higher peripheral neuropathy (e.g., numbness, tingling, and/or pain in distal extremities)
• More than one prior chemotherapy regimen for metastatic disease (prior adjuvant chemotherapy or any number of prior hormonal therapies are allowed)
• Chemotherapy, immunotherapy or radiotherapy within 2 weeks of Study Day 1 or not having recovered from significant treatment-related side effects due to agents administered previously; patients who have receive nitrosoureas and mitomycin C therapy are required to observe the washout period of 6 weeks prior to study drug infusion on Study Day 1
• Allergy to polysorbate 80 or drugs containing polyoxyethylated castor oil (e.g. cyclosporine)
• Symptomatic or clinically active Central Nervous System (CNS) disease
• Major surgery within 4 weeks of Study Day 1
• Female patients pregnant or nursing
• All patients of reproductive potential must agree to use appropriate non-hormonal form of contraception
• Uncontrolled intercurrent disease (e.g., diabetes, hypertension, thyroid disease)
• Any history of angina pectoris, coronary artery disease or cerebrovascular accident, or transient ischemic attack
• A history of any condition requiring anti-platelet therapy (e.g., phosphodiesterase inhibitors, adenosine diphosphate receptor antagonists) with the exception of general cardiovascular prophylaxis with aspirin
• Cardiac arrhythmia requiring medical therapy
• Serious non-healing wound (including wound healing by secondary intention, ulcer, or bone fracture)
• Requirement for chronic daily steroid use
• Known chronic infection with Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV)