Pazopanib Hydrochloride in Treating Patients With Metastatic Urethral Cancer or Bladder Cancer That Has Relapsed or Not Responded to Treatment
Pazopanib Hydrochloride in Treating Patients With Metastatic Urethral Cancer or Bladder Cancer That Has Relapsed or Not Responded to Treatment
RATIONALE: Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the
 enzymes needed for cell growth and by blocking blood flow to the tumor.

 PURPOSE: This phase II trial is studying how well pazopanib hydrochloride works in treating
 patients with or metastatic urothelial cancer or bladder cancer that has relapsed or not
 responded to treatment.
OBJECTIVES:

 Primary

 -  To evaluate the activity of daily oral doses of pazopanib hydrochloride monotherapy in
 patients with relapsed/refractory metastatic urothelial carcinoma or transitional cell
 tumors.

 Secondary

 -  To evaluate the safety and tolerability of pazopanib hydrochloride monotherapy in a
 population of chemotherapy pretreated patients.

 -  To assess progression-free survival of these patients.

 Tertiary

 -  To evaluate the ability of whole-body 18FDG-PET to image metastases and monitor tumor
 response and to determine the rate of concordance with CT imaging and RECIST response
 criteria.

 -  To evaluate the relationship existing between tumor response measured by 18FDG-PET and
 progression-free survival.

 OUTLINE: This is a multicenter study.

 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.

 Patients undergo whole-body 18FDG-PET at baseline and periodically.

 After completion of study treatment, patients are followed for 2 years.
DISEASE CHARACTERISTICS:

 -  Histologically confirmed diagnosis of transitional cell tumors of the bladder or the
 urothelium

 -  Metastatic disease

 -  Relapsed or refractory disease

 -  Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 2 cm by
 conventional techniques or ≥ 1 cm by spiral CT scan

 -  Must have failed ≥ 1 cisplatin-based conventional chemotherapy regimen for metastatic
 disease (neoadjuvant/adjuvant therapy excluded)

 -  No history or clinical evidence of CNS metastases or leptomeningeal carcinomatosis,
 except for individuals who were previously treated for CNS metastases, are
 asymptomatic, and have had no requirement for steroids or anti-seizure medication for
 the past 6 months

 PATIENT CHARACTERISTICS:

 -  ECOG performance status 0-1

 -  Life expectancy ≥ 12 weeks

 -  Hemoglobin ≥ 9.0 g/dL

 -  Absolute neutrophil count ≥ 1,000/μL

 -  Platelet count ≥ 75,000/μL

 -  Total bilirubin ≤ 1.5 x upper limit of normal (ULN)

 -  ALT and AST ≤ 2.5 x ULN (≤ 5 x ULN for patients with liver involvement)

 -  Alkaline phosphatase ≤ 4 x ULN

 -  Serum creatinine ≤ 1.5 mg/dL

 -  PT-INR/PTT < 1.5 x ULN

 -  Not pregnant or nursing

 -  Negative pregnancy test

 -  Fertile patients must use effective barrier contraception during and for 3 months
 after completion of study therapy

 -  Able to swallow oral medication

 -  None of the following cardiovascular conditions within the past 6 months:

 -  Cardiac angioplasty or stenting

 -  Myocardial infarction

 -  Unstable angina

 -  Symptomatic peripheral vascular disease

 -  NYHA class III or IV congestive heart failure

 -  Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin
 are permitted)

 -  Uncontrolled hypertension

 -  No history of HIV infection or active chronic hepatitis B or C

 -  No active clinically serious infections > grade 2 NCI-CTC version 4.0

 -  No seizure disorder requiring medication (e.g., steroids or anti-epileptics)

 -  No history of any of the following conditions within the past 6 months:

 -  Cerebrovascular accident

 -  Pulmonary embolism

 -  Untreated deep venous thrombosis

 -  No evidence or history of bleeding diathesis

 -  No known endobronchial lesions or involvement of large pulmonary vessels by tumor

 -  No hemoptysis within the past 6 weeks

 -  No gastrointestinal abnormalities that may increase the risk of GI bleeding or affect
 the absorption of investigational study drug

 -  No other cancer that is distinct in primary site or histology from the cancer being
 evaluated in this study, except cervical carcinoma in situ, treated basal cell
 carcinoma, or any cancer curatively treated > 5 years prior to study entry

 -  No substance abuse, medical, psychological, or social conditions that may interfere
 with the study participation or evaluation of the study results

 -  No concurrent unstable condition that could jeopardize patient safety and their
 compliance in the study

 -  No non-healing wound, fracture, or ulcer within the past 28 days

 -  No major trauma within the past 28 days

 -  No known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
 chemically related to pazopanib hydrochloride

 PRIOR CONCURRENT THERAPY:

 -  See Disease Characteristics

 -  Recovered from all prior therapy

 -  At least 14 days since prior radiotherapy, except palliative radiotherapy

 -  At least 14 days since tumor embolization

 -  At least 14 days or 5 half-lives (whichever is longer) of a drug since prior
 chemotherapy, immunotherapy, biologic therapy, investigational therapy, or hormonal
 therapy

 -  At least 3 weeks since prior biologic response modifiers (e.g., G-CSF)

 -  G-CSF and other hematopoietic growth factors may be used in the management of
 acute toxicity (e.g., febrile neutropenia) when clinically indicated or at the
 discretion of the investigator, however they may not be used to avoid a required
 dose reduction

 -  Chronic erythropoietin allowed provided no dose adjustment is undertaken within 2
 months prior to the study or during the study

 -  No prior pazopanib hydrochloride

 -  No coronary artery by-pass graft surgery within the past 6 months

 -  No major surgery within the past 28 days

 -  Concurrent coumadin or heparin for therapeutic anticoagulation allowed provided that
 no prior evidence of underlying abnormality in PT-INR/PTT parameters exist

 -  Not concurrently undergoing renal dialysis