Sunitinib in Treating Patients With Progressive Metastatic Transitional Cell Cancer of the Urothelium

OBJECTIVES:

Primary

• Determine the response rate in patients with progressive metastatic transitional cell carcinoma of the urothelium treated with sunitinib malate.
• Determine the safety of this regimen in these patients.

Secondary

• Determine the time to disease progression in patients treated with this regimen.

• To determine time to tumor progression (TTP) for sunitinib malate on a continuous dosing schedule for treatment of metastatic urothelial carcinoma.
• To estimate sunitinib and SU012662 trough plasma concentration (Ctrough) data for the continuous daily schedule and to determine potential association with efficacy and safety.

DISEASE CHARACTERISTICS:

• Histologically confirmed transitional cell carcinoma of the urothelium, including 1 of the following sites:

• Bladder
• Urethra
• Ureter
• Renal pelvis
• Progressive metastatic disease

• Progressive disease defined as new or progressive lesions on cross-sectional imaging
• Progressed despite prior treatment with cytotoxic chemotherapy
• Measurable disease
• Previously treated disease, as defined by the following:

• Received treatment with 1-4 cytotoxic agents
• Prior therapy must have included ≥ 1 of the following:

• Cisplatin
• Carboplatin
• Paclitaxel
• Docetaxel
• Gemcitabine hydrochloride
• Prior cytotoxic agents in the perioperative or metastatic setting allowed and may have been administered sequentially (e.g., first-line treatment followed by second-line treatment at time of progression) or all as part of a single regimen
• No symptomatic CNS metastases

PATIENT CHARACTERISTICS:

• Karnofsky performance status 60-100%
• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 8.0 g/dL
• Bilirubin ≤ 1.5 mg/dL (unless Gilbert's disease is present)
• AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN if liver function abnormalities are due to underlying malignancy)
• Creatinine ≤ 2.0 mg/dL
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• None of the following within the past 6 months:

• Myocardial infarction
• Severe or unstable angina
• Coronary or peripheral artery bypass graft
• Symptomatic congestive heart failure
• Cerebrovascular accident or transient ischemic attack
• Pulmonary embolism
• No ongoing cardiac dysrhythmias ≥ grade 2
• No prolonged QTc interval on baseline ECG
• No uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg despite optimal medical therapy
• No preexisting thyroid abnormality (i.e., thyroid function tests that cannot be maintained in the normal range with medication)
• No known HIV- or AIDS-related illness or other active infection

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy or chemotherapy
• At least 4 weeks since prior major surgery
• No other concurrent investigational drugs
• No concurrent participation in another clinical trial (supportive care trials or non-treatment trials [e.g., quality of life] allowed)
• No concurrent therapeutic doses of warfarin (low-dose warfarin ≤ 2 mg once daily for thromboembolic prophylaxis allowed)