A Study of Herceptin (Trastuzumab) in Combination With Avastin (Bevacizumab) and Sequential Xeloda (Capecitabine) or Docetaxel in Patients With HER2-Positive Locally Recurrent or Metastatic Breast Cancer

A Single Arm, Open-label Study to Evaluate the Efficacy on Tumor Response and the Safety of Bevacizumab and Trastuzumab Combination and Sequential Capecitabine in Patients With HER2 +Ive Locally Recurrent or Metastatic Breast Cancer After Early Relapse to Adjuvant Trastuzumab-containing Therapy

This single arm, open-label study will evaluate the safety and efficacy of Herceptin in combination with Avastin and sequential Xeloda in patients with locally recurrent or metastatic HER2-positive breast cancer after early relapse on adjuvant Herceptin therapy. Patients will receive Herceptin at a loading dose of 8mg/kg iv followed by 6mg/kg iv every three weeks, and Avastin 15mg/kg every 3 weeks. At first sign of disease progression Xeloda 1000mg/m2 bid po will be added on days 1-14 of each cycle, or docetaxel (100mg/m2 iv every 3 weeks) if Xeloda is not indicated for a patient. Anticipated time on study treatment is until disease-progression on second line treatment and target sample size is <100.

Inclusion Criteria:

• male or female patients, age >/=18 years
• locally recurrent or metastatic HER2-positive breast cancer
• disease progression during or up to 12 months after prior adjuvant therapy with trastuzumab
• LVEF >/=55% at baseline

Exclusion Criteria:

• prior treatment with bevacizumab or capecitabine
• anthracyclines in prior adjuvant or neoadjuvant treatment exceeding cumulative dose of 360mg/m2 for doxorubicin and 720mg/kg for epirubicin
• chronic daily treatment with corticosteroids (>10mg/day methylprednisolone equivalent; excluding inhaled corticosteroids), or aspirin (>325mg/day), or clopidogrel (>75mg/day)
• clinically significant cardiac disease, or cardiac toxicity during previous trastuzumab therapy
• evidence of spinal cord compression or CNS metastasis
• history of other malignancy, unless disease-free for >/=5 years or treated curatively for carcinoma in situ of the cervix or non-melanomatous skin cancer