Trial of Chemotherapy and Avastin as Treatment for Women With Breast Cancer at 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