Vanderbilt-Ingram Cancer Center

Patients that have breast cancer that has returned after it had been treated, or breast cancer that had already spread to other parts of the body at the time it was diagnosed, and who have not received more than one chemotherapy regimen for their locally recurrent or metastatic breast cancer are eligible to take part in this study. The purpose of this study is to find out whether a drug called GDC-0941 can be safely combined with paclitaxel (Taxol), with and without bevacizumab (Avastin) or trastuzumab (Herceptin). Bevacizumab, paclitaxel, and trastuzumab are being used to treat breast cancer patients. These drug combinations are intended to treat patients with locally recurrent or metastatic breast cancer. Genentech manufactures GDC-0941, Bevacizumab and Trastuzumab. Bristol-Myers Squibb manufactures Paclitaxel. GDC 0941 is an investigational drug that inhibits a protein called PI3-kinase that may be involved in the growth and spread of some cancers. In animal studies and lab experiments, GDC-0941 has been shown to prevent or slow the growth of many different types of human cancer cells. It is now being tested in research studies in people with advanced cancer. This study is designed to determine what effects these drug combinations have on patients with locally recurrent or metastatic breast cancer.

Criteria
 Inclusion Criteria:

 • Confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease

 • Adequate organ and bone marrow function as assessed by laboratory tests

 • Evaluable disease or disease measurable per Response Evaluation Criteria in Solid Tumors (RECIST)

 • Agreement to use an effective form of contraception for the duration of the study

 Exclusion Criteria:

 • History of Grade >/= 3 fasting hyperglycemia

 • History of diabetes requiring regular medication

 • History of malabsorption syndrome or other condition that would interfere with enteral absorption

 • Any condition requiring full-dose anticoagulants, such as warfarin, heparin, or thrombolytic agents

 • Prior anti-cancer therapy (e.g., chemotherapy, biologic therapy, or hormonal therapy) within a specified timeframe of the first dose of study treatment

 • Uncontrolled current illness

 • Active autoimmune disease requiring the equivalent of >10 mg/day of prednisone

 • Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, or current known active infection with HIV, hepatitis B virus, or hepatitis C virus

 • Known HIV infection

 • New York Heart Association (NYHA) Class II or greater congestive heart failure

 • Active ventricular arrhythmia requiring medication

 • Pregnancy, lactation, or breastfeeding

 • Known significant hypersensitivity to study drugs or excipients

 • History of arterial thromboembolic disease within 6 months of first study treatment

 • No more than two prior chemotherapy regimens for metastatic disease

 • No prior taxane therapy for metastatic disease