Capecitabine and Bevacizumab ± Vinorelbine in Metastatic Breast Cancer (CARIN)

Key Inclusion Criteria:

• Written informed consent.
• Able to comply with the protocol.
• ECOG Performance status 0 - 2.
• Life expectancy more than 12 weeks.
• Known ER / PR status.
• Confirmed HER2/neu-negative, adenocarcinoma of the breast with measurable or non-measurable locally recurrent or metastatic disease, who are candidates for chemotherapy.
• Previous (neo)adjuvant chemotherapy is allowed provided that the last dose of chemotherapy was applied more than 6 months prior to randomization.
• Previous adjuvant radiotherapy is allowed as part of the treatment of early breast cancer provided that no more than 30% of marrow-bearing bone was irradiated.
• No signs and symptoms of CHF.
• Adequate hepatic and renal function values.
• Adequate hematologic function values.

Key Exclusion Criteria:

• Pregnant or lactating females.
• Previous chemotherapy for metastatic or locally recurrent breast cancer.
• Previous radiotherapy for the treatment of metastatic disease (unless given for the relief of metastatic bone pain)
• Evidence of spinal cord compression or current evidence of central nervous system (CNS) metastases.
• Major surgical procedure, open biopsy or significant traumatic in-jury within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study treatment.
• History or evidence of inherited bleeding diathesis or coagulopathy with the risk of bleeding.
• Uncontrolled hypertension (systolic > 150 mmHg and/or diastolic > 100 mmHg). 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.
• Non-healing wound, active peptic ulcer or bone fracture.
• History of abdominal fistula, or any grade 4 nongastrointestinal fistula, gastrointestinal perforation or intrabdominal abscess within 6 months of randomization.
• Active infection requiring i.v. antibiotics at randomization.
• Clinically significant malabsorption syndrome or inability to take oral medication.
• Known hypersensitivity to any of the study drugs or excipients.
• Concurrent treatment with any drug interfering with study medication. Concurrent participation in another clinical trial. Prior participation is allowed when the last study medication was applied more than 4 weeks prior to randomization.