Pazopanib in Treating Patients With Metastatic Urothelial Cancer

This is an interventional treatment trial for Distal Urethral Cancer Read More

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