Treatment With Pazopanib for Neoadjuvant Breast Cancer

Inclusion Criteria

• •The patient must have consented to participate and must have signed and dated an appropriate IRB-approved consent form that conforms to federal and institutional guidelines for the study treatment and submission of tumor and blood samples required for the FB-6 correlative science studies
• •The ECOG performance status must be 0 or 1
• •Patients must have the ability to swallow oral medication.
• •The diagnosis of invasive adenocarcinoma of the breast must have been made by core needle biopsy or limited incisional biopsy.
• •Patients must have ER analysis performed on the primary tumor prior to randomization. If ER analysis is negative, then PgR analysis must also be performed. (Patients are eligible with either hormone receptor-positive or hormone receptor-negative tumors.)
• •Patients must have clinical stage IIIA, IIIB, or IIIC disease with a mass in the breast or axilla measuring at least 2.0 cm by physical exam, unless the patient has inflammatory breast cancer, in which case measurable disease by physical exam is not required.
• •Adequate organ function
• •LVEF assessment by 2-D echocardiogram or MUGA scan performed within 3 months prior to study entry must be greater or equal to 50% regardless of the facility's LLN.
• •ECG performed within 4 weeks before study entry must demonstrate a QTc interval that is less than or equal to 0.47 seconds.
• •The TSH level must be within normal limits for the laboratory.
• •Requirement for chronic use of any of the prohibited medications or substances
• •Previous therapy with anthracyclines, taxanes, or pazopanib for any malignancy.
• •Treatment including RT, chemotherapy, and/or targeted therapy, administered for the currently diagnosed breast cancer prior to study entry.
• •Continued therapy with any hormonal agent such as raloxifene, tamoxifen, or other SERM.
• •Any sex hormonal therapy, e.g., birth control pills and ovarian hormone replacement therapy
• •History of hepatitis B or C.
• •Symptomatic pancreatitis or asymptomatic greater or equal to grade 2 elevation of amylase or lipase as per NCI CTCAE v3.0.
• •History of documented pancreatitis.
• •Uncontrolled hypertension defined as systolic BP greater than 140 mmHg or diastolic BP greater greater than 90 mmHg, with or without anti-hypertensive medication.
• •History of hypertensive crisis or hypertensive encephalopathy.
• •Cardiac disease that would preclude the use of any of the drugs included in the FB-6 treatment regimen.
• •History of TIA or CVA.
• •History of any arterial thrombotic event within 12 months prior to study entry.
• •Pulmonary embolism or DVT within 6 months prior to study entry.
• •Symptomatic peripheral vascular disease.
• •Any significant bleeding within 6 months prior to study entry, exclusive of menorrhagia in premenopausal women.
• •Known bleeding diathesis, coagulopathy, or requirement for therapeutic doses of coumadin.
• •Serious or non-healing wound, skin ulcers, or bone fracture.
• •Gastroduodenal ulcer(s) determined by endoscopy to be active.
• •History of GI perforation, abdominal fistulae, or intra-abdominal abscess.
• •Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease significantly affecting gastrointestinal function.
• •Sensory/motor neuropathy greater or equal to grade 2, as defined by the NCI's CTCAE v3.0.
• •Conditions that would prohibit intermittent administration of corticosteroids for paclitaxel premedication.
• •Anticipation of need for major surgical procedures (other than the required breast surgery) during the course of study therapy and for at least 3 months following the last dose of pazopanib.
• •Pregnancy or lactation at the time of study entry.
• •Other nonmalignant systemic disease that would preclude the patient from receiving study treatment or would prevent required follow-up.
• •Known immediate or delayed hypersensitivity reaction to doxorubicin, cyclophosphamide, paclitaxel, pazopanib, or drugs chemically related to pazopanib.
• •Use of any investigational agent within 4 weeks prior to enrollment in the study.