Investigational Drug in Combination With Two Chemotherapy Drugs in Women With Locally Recurrent or Metastatic Breast Cancer

Exclusion Criteria

• •Disease Related:
• •Current or prior history of central nervous system metastasis.
• •Common Terminology Criteria for Adverse Events (CTCAE) v. 3.0 peripheral neuropathy ≥ grade 2 at enrollment.
• •Average systolic blood pressure \> 150 mm Hg or average diastolic blood pressure \> 90 mm Hg (average blood pressure of the 3 separate blood pressure values measured according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure.
• •History of arterial or venous thrombosis within 1 year prior to enrollment.
• •History of bleeding diathesis or bleeding within 14 days of enrollment.
• •Major surgical procedure within 4 weeks (28 days) prior to enrollment.
• •Minor surgical procedure, placement of access device, or fine needle aspiration within 7 days of enrollment.
• •Known positive test for human immunodeficiency virus (HIV), hepatitis C, or malignancy (other than in situ cervical cancer, or basal cell cancer of the skin), unless treated with curative intent and without evidence of disease for ≥ 3 years before study enrollment.
• •Clinically significant cardiac disease within 12 months of study enrollment, including myocardial infarction, unstable angina, grade II or greater peripheral vascular disease, cerebrovascular accident, transient ischemic attack, congestive heart failure, or ongoing arrhythmias requiring medication or pacemaker.
• •Non-healing wound, ulcer or fracture.
• •Ongoing or active infection.
• •Known chronic hepatitis.
• •Medications:
• •Currently or previously treated with small molecule inhibitors of VEGF including, but not limited to, SU11248 (sunitinib), PTK787 (vatalinib), AZD 2171, AZD 6474, AEE-788, BAY 43-9006 (sorafenib) and motesanib.
• •Treatment with rifampin, carbamazepine, rifabutin or phenobarbital within 14 days prior to study enrollment.
• •Treatment with strong CYP 3A inhibitors or inducers such as ketoconazole, itraconazole, fluconazole, clarithromycin, erythromycin, nefazodone, or any HIV protease inhibitors within 7 days prior to study enrollment.
• •Treatment with immune modulators such as cyclosporine and tacrolimus within 7 days prior to study enrollment.
• •Treatment with herbal medications containing St. John's Wort within 7 days prior to study enrollment.
• •Concomitant therapy with any hormonal agent such as raloxifene, tamoxifen, or other selective estrogen receptor modulators (SERMS), given for breast cancer prevention or for osteoporosis. Patients must have discontinued these agents prior to enrollment.
• •General:
• •Known hypersensitivity to any study medications (motesanib, and Chinese Hamster Ovary cell products or other human or humanized recombinant proteins) or Cremaphor.
• •Any condition which in the investigator's opinion makes the patient unsuitable for the study participation. This includes substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
• •Participation in other investigational device drug trials, or administration of other investigational treatments within 30 days prior to study enrollment.
• •Pregnant (i.e., positive beta-human chorionic gonadotropin test)
• •Not willing to use a highly effective method of birth control (i.e. those which result in low failure rates, less than 1% per year), such as nonhormonal IUD, condoms, sexual abstinence or vasectomised partner.
• •\*\*Contraception must be used during the study and for 6 months after last dose of study treatment\*\*
• •Unable to swallow oral medications.
• •Inability to comply with protocol and/or not available for follow-up assessments.
• •Males of any age.