Intervention: Pazopanib Hydrochloride
Trial phase: Phase 2
SMILES: Cc1ccc(Nc2nccc(N(C)c3ccc4c(C)n(C)nc4c3)n2)cc1S(N)(=O)=O.Cl
Sex: All
Age groups: Adult | Older Adult
Healthy volunteers: No
Participants at risk: 21
Group description: Patients receive oral pazopanib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

pazopanib hydrochloride: Given orally

pharmacological study: Correlative studies

laboratory biomarker analysis: Correlative studies
Eligibility criteria:
Criteria:

No prior bevacizumab
Histologically or cytologically confirmed invasive breast carcinoma (recurrent or metastatic disease)
Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques or >= 10 mm by spiral CT scan
Patients who may still benefit from hormonal therapy are ineligible (patients with hormone receptor-positive breast cancer should have received appropriate sequential hormonal therapy for metastatic disease until disease progression)
Patients with HER-2 positive disease who have not yet received trastuzumab (Herceptin®) to maximal benefit are ineligible (patients with disease progression during trastuzumab therapy are eligible)
No known brain metastases
ECOG performance status (PS) 0-1 or Karnofsky PS 60-100%
Life expectancy > 12 weeks
Absolute neutrophil count >= 1,500/mm³
Platelets >=100,000/mm³
Total bilirubin normal (exception made for patients with known Gilbert's disease)
AST/ALT =< 2.5 times upper limit of normal (ULN)
No proteinuria > +1 on two consecutive dipsticks taken >= 1 week apart
PT/INR/PTT =< 1.2 times ULN
No allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib or other study agents
No QTc prolongation (defined as a QTc interval >= 500 msecs) or other significant ECG abnormalities
No condition (e.g., gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation, or active peptic ulcer disease) that would impair ability to swallow and retain study drug
No poorly controlled hypertension (systolic blood pressure [BP] >= 140 mm Hg or diastolic BP >= 90 mm Hg) Initiation or adjustment of BP medication is allowed prior to study entry provided that the average of 3 BP readings prior to study entry is < 140/90 mm Hg
No serious or non-healing wound, ulcer, or bone fracture
No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the last 4 weeks
No cerebrovascular accident within the last 6 months
No myocardial infarction, cardiac arrhythmia, hospital admission for unstable angina within the last 12 weeks
No venous thrombosis within the last 12 weeks
No NYHA class III-IV heart failure Patients with a history of class II heart failure may be considered eligible provided they are asymptomatic on treatment
No concurrent uncontrolled illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would preclude study compliance
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C), radiotherapy, or surgery
No cardiac angioplasty or stenting within the last 12 weeks
No more than 1 prior chemotherapy regimen for recurrent disease
No prior surgical procedures affecting absorption
No CYP2C9 substrates during or for 1-2 weeks after completion of study treatment, including any of the following:

Therapeutic warfarin Low molecular weight heparin or prophylactic low-dose warfarin are allowed

No CYP2C9 substrates during or for 1-2 weeks after completion of study treatment, including any of the following:

Erectile dysfunction agents: sildenafil, tadalafil, or vardenafil
Antiarrhythmics: bepridil, flecainide, lidocaine, mexilitine, amiodarone, or quinidine
Immune modulators: cyclosporine, tacrolimus, or sirolimus
Miscellaneous: theophylline, quetiapine, or risperidone

No CYP2C9 substrates during or for 1-2 weeks after completion of study treatment, including any of the following:

Oral hypoglycemics: glipizide, glyburide, or tolbutamide
Ergot derivatives: dihydroergotamine, ergonovine, ergotamine, or methylergonovine
Neuroleptics: pimozide
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent investigational agents
No other concurrent anticancer therapy
WBC >= 3,000/mm³
No more than 2 prior palliative systemic chemotherapy regimens for de novo metastatic disease
Creatinine normal OR creatinine clearance >= 60 mL/min
At least 3 months since prior trastuzumab