A Phase II Study of Adjuvant Gemcitabine/Capecitabine and Bevacizumab for Patients Treated Neoadjuvantly Chemotherapy for Early Stage Breast Cancer With High Risk for Relapse

Inclusion Criteria:

General health

- Women Age >18.

- ECOG Performance status 0-1

- Life expectancy must be 3 months. Clinical stage

- Histologically or cytologically adenocarcinoma of breast

- Pre-operative stage II-III per AJCC 6th edition, based on baseline evaluation by
clinical examination, breast imaging, and/or preoperative work-up.

- Evidence of residual invasive breast cancer or node positive disease following
neoadjuvant chemotherapy.

Prior Therapy

- Patients must have received primary (neoadjuvant) chemotherapy for local or
locoregional breast cancer containing an anthracycline and a taxane.

- Patients must have completed definitive resection of primary tumor with adequate
excision of gross disease.

- Patients must have residual invasive carcinoma in the breast and/or residual
carcinoma in one or more regional nodes following preoperative chemotherapy.

Adequate hematologic and metabolic parameters within four weeks of study entry defined
as:

- Absolute neutrophil count ≥1,500/mm3 Platelets ≥ 150,000/mm3

- Total bilirubin ≤ 2.0 mg/dL

- Serum creatinine ≤ 2x upper limit of normal

- Serum calcium ≤1.5x upper normal limit Concurrent treatments

- Current use of anti-coagulants is allowed as long as patients have been on a stable
dose for more than 2 weeks with stable INR.

- Chronic therapy with full dose aspirin up to 325 mg/day or standard non-steroidal
anti-inflammatory agents is allowed.

Informed consent

- Provision of signed informed consent.

Exclusion Criteria:

Prior therapy

- No prior gemcitabine, continuous infusion 5-FU, or oral fluoropyrimidine
(capecitabine, UFT, S-1, 5-FU/eniluracil, etc.)

- No known hypersensitivity to capecitabine or prior unanticipated severe reaction to
(capecitabine, UFT, S-1, 5-FU/eniluracil, etc.) therapy or known hypersensitivity
to 5-fluorouracil.

- No concurrent or prior endocrine therapy as adjuvant treatment.

- No prior breast radiation

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

- Stage IV breast cancer

- Patients must not have evidence of metastatic disease at enrollment. Women of
child-bearing potential.

- Nonpregnant and nonlactating.

- Women of child-bearing potential must have a negative serum pregnancy test and must
agree to an effective means of contraception during the entire study period.

Concurrent medical conditions:

- No other active cancers, except non-melanoma skin cancers.

- No serious infection or other serious underlying medical condition that would
otherwise impair their ability to receive protocol treatment.

- Patients with clinically significant medical or psychiatric problems which may
interfere with treatment on study.

Avastin-specific exclusions:

- Inadequately controlled hypertension (defined as systolic blood pressure 150 and/or
diastolic blood pressure > 100 mmHg on antihypertensive medications)

- Any prior history of hypertensive crisis or hypertensive encephalopathy

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

- Known CNS disease

- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

- Symptomatic peripheral vascular disease

- Evidence of bleeding diathesis or coagulopathy

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

- Core biopsy or other minor surgical procedure, excluding placement of a vascular
access device, within 7 days prior to study enrollment

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

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

- Proteinuria at screening as demonstrated by urine dipstick for proteinuria ≥ 2+
(patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline
should undergo a 24 hour

- urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).

- Known hypersensitivity to any component of bevacizumab any history of stroke or
transient ischemic attack at any time

- History of myocardial infarction or unstable angina within 12 months of study
enrollment Inability to comply with study and/or follow-up procedures