Pazopanib in Treating Patients With Metastatic Urothelial Cancer

Inclusion Criteria

• •Histologically or cytologically confirmed transitional cell cancer of the urothelium or bladder
• •* Metastatic disease
• •Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan
• •No known brain metastases
• •ECOG performance status 0-2
• •Life expectancy ≥ 12 weeks
• •Platelet count ≥ 100,000/mm\^3
• •WBC ≥ 3,000/mm\^3
• •Absolute neutrophil count ≥ 1,500/mm\^3
• •Bilirubin normal
• •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
• •No proteinuria \> 1+ on two consecutive dipsticks measured ≥ 1 week apart
• •Not pregnant or nursing
• •Negative pregnancy test
• •Fertile patients must use effective contraception
• •No history of allergic reactions attributed to compounds of similar chemical or biological composition to pazopanib hydrochloride or other agents used in the study
• •No condition that impairs the ability to swallow and retain pazopanib hydrochloride tablets, including any of the following:
• •* Gastrointestinal tract disease resulting in an inability to take oral medication
• •* Requirement for IV alimentation
• •* Prior surgical procedures affecting absorption
• •* Active peptic ulcer disease
• •No uncontrolled illness that would limit compliance with study therapy including, but not limited to, any of the following:
• •* Ongoing or active infection
• •* Psychiatric illness or social situations
• •No QTc prolongation (defined as a QTc interval ≥ 480 msecs) or other significant ECG abnormalities (e.g., frequent ventricular ectopy, evidence of ongoing myocardial ischemia)
• •No other conditions, including any of the following:
• •* Serious or non-healing wound, ulcer, or bone fracture
• •* Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• •* Cerebrovascular accident within the past 6 months
• •* Myocardial infarction, cardiac arrhythmia, or admission for unstable angina within the past 12 weeks
• •* Venous thrombosis within the past 12 weeks
• •* New York Heart Association (NYHA) class III or IV heart failure
• •* Asymptomatic NYHA class II heart failure on treatment allowed
• •No other active second malignancy other than non-melanoma skin cancer
• •* Patients are not considered to have an active malignancy if they have completed anti-cancer therapy and are considered by their physician to be ≤ 30% risk of relapse
• •At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• •At least 4 weeks since prior radiotherapy
• •Prior palliative radiotherapy to metastatic lesions allowed provided there is ≥ 1 measurable and/or evaluable lesion(s) that has not been irradiated
• •At least 4 weeks since prior surgery
• •One prior chemotherapy regimen for metastatic urothelial or bladder cancer
• •More than 12 weeks since prior cardiac angioplasty or stenting
• •Prior adjuvant or neoadjuvant therapy allowed
• •No prior experimental treatment for metastatic disease
• •No other prior or concurrent investigational agents
• •No concurrent combination antiretroviral therapy for HIV-positive patients
• •No concurrent CYP2C9 substrates, including any of the following:
• •* Anticoagulants (e.g., warfarin \[therapeutic doses only\])
• •* Low molecular weight heparin and prophylactic low-dose warfarin (≤ 2 mg daily) allowed
• •* Oral hypoglycemics (e.g., glipizide, glyburide, tolbutamide, glimepiride, or nateglinide)
• •* Ergot derivatives (e.g., dihydroergotamine, ergonovine, ergotamine, or methylergonovine)
• •* Antipsychotics (e.g., pimozide or clozapine)
• •* Erectile dysfunction agents (e.g., sildenafil, tadalafil, or vardenafil)
• •* Antiarrhythmics (e.g., bepridil, flecainide, lidocaine, mexiletine, amiodarone, quinidine, or propafenone)
• •* Immune modulators (e.g., cyclosporine, tacrolimus, or sirolimus)
• •* Miscellaneous drugs (e.g., theophylline, quetiapine, risperidone, tacrine, or atomoxetine)
• •No other concurrent anticancer agents or therapies
• •No concurrent medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes