Neo-adjuvant Therapy With Anastrozole Plus Pazopanib in Stage II and III ER+ Breast Cancer

Exclusion Criteria

• •Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
• •Hemoglobina \>= 10 g/dL (5.6 mmol/L); subjects may not have had a transfusion within 7 days of screening assessment
• •Platelets \>= 100 x 10\^9/L
• •Prior malignancy; note: subjects who have had another malignancy and have been disease-free for \>= 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
• •Known distant metastases at any site; history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis
• •Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
• •Active peptic ulcer disease
• •Known intraluminal metastatic lesion/s with risk of bleeding
• •Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or
• •Other gastrointestinal conditions with increased risk of perforation
• •History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of registration to the study; clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
• •Malabsorption syndrome
• •Major resection of the stomach or small bowel
• •Presence of uncontrolled infection
• •Corrected QT interval (QTc) \> 480 msecs using Bazett's formula
• •History of any one or more of the following cardiovascular conditions within 6 months of registration on the study:
• •Cardiac angioplasty or stenting
• •Myocardial infarction
• •Unstable angina
• •Coronary artery bypass graft surgery
• •Symptomatic peripheral vascular disease
• •Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
• •Poorly controlled hypertension \[defined as systolic blood pressure (SBP) of \>= 140 mmHg or diastolic blood pressure (DBP) of \>= 90 mm Hg\]; note: initiation of adjustment of antihypertensive medication(s) is permitted prior to study entry
• •History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months of registration on the study; note: subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks of registration to the study are eligible
• •Prior major surgery or trauma within 28 days of registration on the study prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major)
• •Evidence of active bleeding or bleeding diathesis
• •Hemoptysis within 8 weeks of registration to the study
• •Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
• •Treatment with any of the following anti-cancer therapies for the current diagnosis of stage 2-3 estrogen positive breast carcinoma:
• •Radiation therapy, surgery or tumor embolization within 14 days prior to first dose of pazopanib OR
• •Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
• •Any ongoing toxicity from prior anti-cancer therapy that is \> Grade 1 and/or that is progressing in severity, except alopecia
• •Concomitant anti-cancer therapies are not permitted
• •Patients may not be receiving any other investigational agents
• •History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pazopanib or Anastrozole used in the study
• •Concomitant use of medications or substances that are inhibitors or inducers of strong CYP3A4 inhibitors are ineligible
• •Concomitant: the concomitant use of strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin) may increase pazopanib concentrations and should be avoided; if coadministration of a strong CYP3A4 inhibitor is warranted, reduce the dose of pazopanib to 400 mg; further dose reductions may be needed if adverse effects occur during therapy; this dose is predicted to adjust the pazopanib AUC to the range observed without inhibitors; however, there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inhibitors; grapefruit juice should be avoided as it inhibits CYP3A4 activity and may also increase plasma concentrations of pazopanib
• •Concomitant strong CYP3A4 inducer: the concomitant use of strong CYP3A4 inducers (e.g. rifampin) may decrease pazopanib concentrations and should be avoided