Trastuzumab (Herceptin), Bevacizumab, and Docetaxel (Taxotere) Trial in Stage IV Metastatic Breast Cancer (MBC) Patients

Rationale: Antibodies are proteins that are normally part of the immune system that bind to
foreign agents in the body. Researchers manufacture antibodies outside of the human body that
bind to specific targets such as proteins in cancer cells. Herceptin is a monoclonal antibody
that binds to the human epidermal growth factor receptor (HER-2), and can kill HER2-positive
cancer cells. Herceptin is used to treat breast cancer that is HER2-positive, and has spread
after treatment with other drugs. Bevacizumab is a signal transduction inhibitor that works
by preventing the growth of new blood vessels from surrounding tissue into tumors.
Bevacizumab specifically inhibits the vascular endothelial growth factor (VEGF), a substance
made by cells that stimulates new blood vessel formation. Research indicates that HER-2
signaling helps to induce VEGF expression. Therefore, cancer treatments targeting both HER-2
and VEGF may improve anti-cancer efficacy in patients. Docetaxel is a chemotherapy agent used
against breast and other types of cancer. The current study builds on previous research
suggesting the safety and potential for efficacy with combination trastuzumab, bevacizumab,
and docetaxel.

Purpose: The primary objectives are to determine the progression free survival and evaluate
the safety of trastuzumab, bevacizumab, and docetaxel. Secondary objectives are to assess
early changes in circulating tumor cells and circulating endothelial cells as predictors of
progression free survival and clinical benefit, as well as to determine the overall clinical
benefit rate.

Treatment: Study participants will be given trastuzumab, bevacizumab, and docetaxel. All
study drugs will be given through intravenous infusions once every 21 days. A cycle is
considered 3 weeks. A minimum of 6 study treatment cycles is required unless study
participants experience disease growth or intolerable toxicity. The decision to stop
docetaxel after 6 cycles is up to the discretion of the treating physician and the patient.
Study participants who are deriving a benefit from the study drugs may continue on
trastuzumab and bevacizumab alone. Several tests and exams will be given throughout the study
to closely monitor study participants.

Inclusion Criteria:

- Histologically confirmed breast cancer with evidence of metastatic disease

- HER2 3+ or FISH (fluorescent in situ hybridization)+

- Age ≥ 18 years

- No prior trastuzumab, except as given in the adjuvant or neoadjuvant setting.

- No prior chemotherapy in the metastatic setting.

Exclusion Criteria:

- CNS (central nervous system) metastases

- Prior radiation therapy within the last 4 weeks

- Pregnant (positive pregnancy test) or lactating women

- Major surgical procedure, open biopsy, non-healing wounds, or significant traumatic
injury within 28 days prior to starting study or anticipation of need for major
surgical procedure during the study

- Minor surgical procedures such as fine needle aspirations or core biopsies within 7
days prior to start of study.