Phase1b to Evaluate Safety of AMG706 in Combination With Paclitaxel or Docetaxel for Breast Cancer

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Female 18 years of age or older.
• Adequate hematologic, renal and hepatic function.
• Competent to comprehend, sign, and date an IRB-approved informed consent form.
• Subjects of childbearing potential and sexually active must provide a negative pregnancy test and use accepted and effective method of contraception.

Exclusion criteria

• Prior taxane-containing treatment within 6 months prior to enrollment.
• Prior treatment including chemotherapy and/or endocrine therapy discontinued < 21 days prior to enrollment.
• More than one prior systemic chemotherapy for locally recurrent or metastatic breast cancer.
• Current or prior history of central nervous system metastases.
• History of arterial or venous thrombosis within 1 year prior to enrollment.
• History of bleeding diathesis or bleeding within 14 days prior to enrollment.
• Radiation therapy to a significant portion of bone marrow or prior history of high-dose chemotherapy requiring bone marrow or stem cell support.
• Hypersensitivity to paclitaxel, docetaxel, or drugs using the vehicle cremophor.
• Prior VEGFr targeted therapies within 30 days of enrollment.
• Any anticoagulant therapy within 7 days prior to enrollment, except for warfarin of less than 2mg per day.
• Clinically significant cardiac disease including myocardial infarction or other cardiovascular related event within 1 year before enrollment.
• Uncontrolled hypertension (systolic >150 mmHg; diastolic > 90 mmHg).
• Known HIV positive, hepatitis C positive or hepatitis B surface antigen positive.
• Prior bevacizumab or trastuzumab therapy within 12 weeks of enrollment.
• Non-healing wound, ulcer or fracture.
• Known history of prior episodes of cholecystitis, prior biliary procedure or prior or ongoing biliary disease.
• Unable to take oral medications.
• Not recovered from previous therapies.
• Major surgery within 28 days prior to enrollment.
• Prior malignancy unless treated with curative intent and without evidence of disease for greater than 3 years before enrollment.
• Peripheral neuropathy grade > 1 per CTCAE version 3.0