A Study of AMG 706 or Bevacizumab, in Combination With Paclitaxel Chemotherapy, as Treatment for Breast Cancer

A Randomized Phase 2 Trial of Double-Blind, Placebo Controlled AMG 706 in Combination With Paclitaxel, or Open-Label Bevacizumab in Combination With Paclitaxel, as First Line Therapy in Women With HER2 Negative Locally Recurrent or Metastatic Breast Cancer

To determine if treatment with paclitaxel plus AMG 706 is superior to paclitaxel plus AMG 706 placebo in subjects with HER2 negative locally recurrent or metastatic breast cancer. Also to estimate differences between treatment with paclitaxel plus AMG 706 and paclitaxel plus bevacizumab.

Inclusion Criteria:

• Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease.
• Measurable disease by RECIST guidelines.
• Tumor (primary or metastatic) must be HER2 negative.
• Adequate organ and hematologic function. Exclusion:
• Taxane treatment within 12 months prior to registration.
• Prior chemotherapy for locally recurrent or metastatic breast cancer (prior endocrine therapy is permitted).
• Prior radiation therapy, radiofrequency ablation, percutaneous cryotherapy or hepatic chemoembolization on all sites of measurable disease.
• Current or prior history of central nervous system metastases.
• Peripheral neuropathy ≥ grade 2 (CTCAE v3.0) at registration.
• History of arterial or venous thrombosis within 1 year prior to registration.
• History of bleeding diathesis or bleeding within 14 days of registration.
• Uncontrolled hypertension (systolic >145 mmHg; diastolic >85 mmHg).
• Clinically significant cardiac disease within 12 months of registration.
• Known HIV positive, hepatitis C positive or hepatitis B surface antigen positive.
• Prior treatment with VEGFr targeted therapies.