2-arm Trial of Paclitaxel Plus Bevacizumab vs. Capecitabine Plus Bevacizumab

Exclusion Criteria

• •1. Previous chemotherapy for metastatic or locally recurrent breast cancer.
• •2. Concomitant hormonal therapy for locally recurrent or metastatic disease. Note: previous hormonal therapy is allowed for adjuvant, locally recurrent or metastatic breast cancer, but must have been discontinued at least 3 weeks prior to randomization.
• •3. Previous radiotherapy for the treatment of metastatic disease (unless given for the relief of metastatic bone pain and with the precautions mentioned above).
• •4. Other primary tumors within the last 5 years, except for adequately controlled limited basal cell carcinoma of the skin, or carcinoma in situ of the cervix.
• •5. Pre-existing peripheral neuropathy NCI CTCAE grade \> 2 at randomization.
• •6. Evidence of spinal cord compression or current evidence of central nervous system (CNS) metastases (even if previously treated). If suspected, the patient should be scanned by CT or magnetic resonance imaging (MRI) within 28 days prior to randomization to rule out spinal / CNS metastases.
• •7. History or evidence upon physical/neurological examination of CNS disease unrelated to cancer, unless adequately treated with standard medical therapy (e.g. uncontrolled seizures).
• •8. Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study treatment.
• •9. Minor surgical procedures, including insertion of an indwelling catheter, within 24 hours prior to randomization.
• •10. Current or recent (within 10 days of first dose of bevacizumab) use of aspirin (\> 325 mg/day) or clopidogrel (\> 75 mg/day).
• •11. Chronic daily treatment with corticosteroids (dose of \> 10 mg/day methylprednisolone equivalent) (excluding inhaled steroids).
• •12. History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
• •13. Uncontrolled hypertension (systolic \> 150 mmHg and/or diastolic \> 100 mmHg).
• •14. Clinically significant (i.e. active) cardiovascular disease, requiring medication during the study and might interfere with regularity of the study treatment, or not controlled by medication.
• •15. Non-healing wound, active peptic ulcer or bone fracture.
• •16. History of abdominal fistula, or any grade 4 non-gastrointestinal fistula, gastrointestinal perforation or intra-abdominal abscess within 6 months of randomization.
• •17. Active infection requiring i.v. antibiotics at randomization.
• •18. Pregnant or lactating females. Serum pregnancy test to be assessed within 7 days prior to study treatment start, or within 14 days with a confirmatory urine pregnancy test within 7 days prior to study treatment start.
• •19. Women of childbearing potential (\< 2 years after the last menstruation) not using effective, non-hormonal means of contraception (intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile) during the study and for a period of 6 months following the last administration of study drug.
• •20. Men who do not agree to use effective contraception during the study and for a period of 6 months following the last administration of study drug.
• •21. Current or recent (within 28 days of randomization) treatment with another investigational drug or participation in another investigational study
• •22. Clinically significant malabsorption syndrome or inability to take oral medication.
• •23. Psychiatric disability judged by the Investigator to be interfering with compliance for oral drug intake.
• •24. Requirement for concurrent use of the antiviral agent sorivudine or chemically related analogues, such as brivudine.
• •25. Evidence of any other disease, metabolic or psychological dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug, or that may affect patient compliance with study routines, or places the patient at high risk from treatment related complications.
• •26. Known Dihydropyrimidine Dehydrogenase (DPD) deficiency or prior unanticipated severe reaction to fluoropyrimidine therapy (with or without documented DPD deficiency)
• •27. Known hypersensitivity to any of the study drugs (including 5-FU) or excipients. Hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies. History of hypersensitivity reactions with drugs formulated in Cremophor® EL (polyoxyethylated castor oil), or previous therapy with bevacizumab.