Pilot Study of GW786034 (Pazopanib), a Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Operable Breast Cancer

Inclusion Criteria:

- Diagnosis of invasive adenocarcinoma of the breast by core needle biopsy or limited
incisional biopsy

- Tumor size >= 1.0 cm as assessed by physical exam or radiographic exam

- Patients with histologically verified local and/or regional recurrence of invasive
breast cancer that is amenable to surgery and meet all eligibility criteria may
participate

- No prior chemotherapy or hormonal therapy for this primary breast cancer

- Able to undergo surgical treatment with either lumpectomy or mastectomy

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- WBC >= 3,000/mm^3

- Platelet count >= 100,000/mm^3

- Bilirubin within normal institutional limits

- AST and ALT =< 2.5 times upper limit of normal (ULN)

- Creatinine normal OR creatinine clearance >= 60 mL/min

- PT/INR/PTT =< 1.2 times ULN

- Urine protein:creatinine ratio =< 1

- Blood pressure =< 140/90

- Eligibility of patients receiving any medications or substances known to affect or
with the potential to affect the activity or pharmacokinetics of GW786034 (pazopanib)
will be determined following review by principal investigator

- Women of child-bearing potential and men must agree to use adequate contraception
prior to study entry and for the duration of study participation

- Any concomitant medications that are associated with a risk of QTc prolongation
and/or Torsades de Pointes should be discontinued or replaced with drugs that do not
carry these risks, if possible; patients who must take medications with a risk or
possible risk of Torsades de Pointes should be watched carefully for symptoms of QTc
prolongation, such as syncope

Exclusion Criteria:

- Patients with locally advanced breast cancer who are not candidates for surgical
resection at time of initial evaluation, including patients with:

- Tumor of any size with direct extension to chest wall or skin (T4a-c)

- Inflammatory breast cancer (T4d)

- Patients with evidence of metastatic disease

- Patients may not be receiving any other investigational agents

- Patients with history of allergic reactions attributed to compounds of similar
chemical or biologic composition to GW786034 or other agents used in the study

- Patients with any of the following conditions are excluded:

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

- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal
abscess within 28 days of treatment

- Any history of cerebrovascular accident (CVA) within the last 6 months

- Current use of therapeutic warfarin. Note: Low molecular weight heparin and
prophylactic low-dose warfarin are permitted; PT/PTT must meet the inclusion
criteria (Section 5.1.8)

- History of myocardial infarction, cardiac arrhythmia, admission for unstable
angina, cardiac angioplasty or stenting within the last 12 weeks

- History of venous thrombosis in last 12 weeks

- Class III or IV heart failure as defined by the NYHA functional classification
system (see Appendix C); a patient who has a history of Class II heart failure
and is asymptomatic on treatment may be considered eligible

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situation that would limit compliance with
study requirements

- Baseline QTc >= 480 msecs or other significant ECG abnormalities

- Patients taking certain medications that act through the CYP450 system

- Patients with any condition that impairs their ability to swallow and retain GW786034

- HIV-positive patients

- Patients who are unable or unwilling to sign a written informed consent document