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: 18
Group description: Patients receive oral pazopanib hydrochloride once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Eligibility criteria:
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