Phase 2 Study of Gemzar, Taxol & Avastin Combination as 1st Line Treatment for Metastatic Breast Cancer

This study will evaluate the time-to-progression (TTP) in patients with metastatic breast
cancer, receiving 1st line therapy with bevacizumab in combination with paclitaxel and
gemcitabine.

Secondary objectives will include response rates and overall survival (OS).

INCLUSION CRITERIA

- Previously-untreated metastatic breast cancer. May have had prior chest wall
irradiation or palliative radiation to bony sites for control of pain or fracture.
These sites of disease, however, will not be considered as sites of measurable
disease.

- Use of bisphosphonates will be permitted.

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Granulocyte count ≥ 1500/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 8.0 g/dL.

- Serum glutamic oxaloacetic transaminase (SGOT) / serum glutamic pyruvic transaminase
(SGPT) ≤ 2.5 x the institutional upper limit of normal (ULN) if alkaline phosphatase
is ≤ ULN or alkaline phosphatase may be up to 4 x ULN if transaminases are ≤ ULN.

- Total bilirubin within institutional limits of normal.

- Calculated creatinine clearance ≥ 30 mL/min using the formula: Ccr(mL/min) = [(140-age
in years) X (wt in kg) X 0.85 (females)]/(72 x serum creatinine in mg/dL)

- ≥ 18 years of age.

- Prior anthracycline treatment in the adjuvant setting or prior chest wall radiation
must have left ventricular ejection fraction (LVEF) within the institutional range of
normal as assessed by pre-treatment multigated acquisition (MUGA) scan or
echocardiogram (ECHO).

- All patients must give signed written informed consent.

- May have received adjuvant therapy as long as therapy complete > 12 months from study
entry.

- Females of childbearing potential must have a negative pregnancy test taken ≤ 2 weeks
prior to study enrollment, and must consent to the use of effective contraception
during the study period and for 6months thereafter.

EXCLUSION CRITERIA

- Receiving hormonal therapy

- Prior treatment for metastatic disease with cytotoxic agents or inhibitors of
epidermal growth factor receptor (EGFR)

- Her2NEU-positive breast cancers, by either immunohistochemistry (IHC) score 3+ or
fluorescence in situ hybridization (FISH)

- Pregnant or lactating.

- Patients have had active malignancies other than breast cancer in the past 5 years
with the exception of in situ carcinoma of the cervix or nonmelanomatous skin cancer.

- Active or unresolved infection.

- Pre-existing peripheral neuropathy > Grade 1.

- Prior history of severe hypersensitivity reaction to paclitaxel, gemcitabine,
bevacizumab or drugs formulated with polysorbate 80.

- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study.

- Blood pressure of >150/100 mmHg

- Unstable angina

- New York Heart Association (NYHA) Grade II or greater congestive heart failure

- History of myocardial infarction within 6 months

- History of stroke within 6 months

- Clinically-significant peripheral vascular disease

- Evidence of bleeding diathesis or coagulopathy

- Presence of central nervous system or brain metastases

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0, anticipation of need for major surgical procedure during the course of
the study

- Minor surgical procedures, fine needle aspirations or core biopsies within 7 days
prior to Day 0

- Urine protein:creatinine ratio ≥ 1.0 at screening

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
within 6 months prior to Day 0

- Serious, non-healing wound, ulcer, or bone fracture

- Inability to comply with study and/or follow-up procedures