Primary
Determine the 4-month progression-free survival rate in patients with progressive regional or metastatic carcinoma of the urothelium treated with sorafenib.
Determine the response rate in patients treated with this drug.
Determine the toxicity of this drug in these patients.
Secondary
Determine time to disease progression and overall survival of patients treated with this drug.
Correlate frequency of raf kinase mutations in tumor specimens with response rate in patients treated with this drug.
Evaluate serum vascular endothelial growth factor levels as potential markers of angiogenesis inhibition in patients treated with this drug.
Determine if there are proteins differentially translated from the genome in patients who respond to treatment with this drug vs patients who do not respond to treatment.
OUTLINE: This is a multicenter study.
Patients receive oral sorafenib twice daily on days 1-56. Courses repeat every 56 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months until 2 years from study entry and then every 6 months until 3 years from study entry.
PROJECTED ACCRUAL: A total of 30-53 patients (20-43 with transitional cell carcinoma [TCC] and 10 with non-TCC) will be accrued for this study within 11-16 months.
Eligibility
Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No

Criteria
DISEASE CHARACTERISTICS:
• Histologically confirmed carcinoma of the urothelium (i.e., renal pelvis, ureter, bladder, or urethra) of 1 of the following histologies:
o Transitional cell carcinoma (TCC)
o Mixed histologies containing a component of TCC
o Non-TCC histologies, including adenocarcinoma or squamous cell carcinoma representing > 90% of the specimen
• Regional or metastatic disease
• Measurable disease
o Previously irradiated lesions may only be used as marker lesions provided there is unequivocal evidence of progression by serial imaging studies
• Progressive disease during 1, and only 1, prior systemic chemotherapy regimen for metastatic disease
o Prior adjuvant or neoadjuvant chemotherapy allowed provided it was completed > 12 months before the initiation of the chemotherapy regimen* that the disease progressed on
 Adjuvant or neoadjuvant chemotherapy is not considered 1 prior regimen NOTE: *Administered in the metastatic setting
• No small cell carcinoma, soft tissue sarcoma, or carcinosarcoma
• No previously untreated CNS metastases
o Previously resected and irradiated CNS metastases with evidence of stable disease allowed
PATIENT CHARACTERISTICS:
Age
• 18 and over
Performance status
• ECOG 0-1
Life expectancy
• Not specified
Hematopoietic
• Granulocyte count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• No evidence of bleeding diathesis
Hepatic
• AST ≤ 2.5 times upper limit of normal
• Bilirubin < 1.5 mg/dL
Renal
• Creatinine < 1.5 mg/dL
Cardiovascular
• No uncontrolled hypertension
• No history of American Heart Association class III or IV cardiovascular disease
• No uncontrolled congestive heart failure
• No ventricular dysrhythmias
Other
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except curatively treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix or clinically unsuspected organ-confined prostate cancer found at the time of cystoprostatectomy
• No active unresolved infection requiring parenteral antibiotics within the past 7 days
• No swallowing dysfunction that would preclude ingesting pills
PRIOR CONCURRENT THERAPY:
Biologic therapy
• No prior systemic biologic response modifier therapy
• More than 4 weeks since prior biologic therapy and recovered
Chemotherapy
• See Disease Characteristics
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
Endocrine therapy
• More than 4 weeks since prior hormonal therapy and recovered
Radiotherapy
• See Disease Characteristics
• At least 2 weeks since prior radiotherapy and recovered
• No concurrent radiotherapy
Surgery
• See Disease Characteristics
• At least 4 weeks since prior major surgery and recovered
Other
• No concurrent therapeutic anticoagulation
o Concurrent prophylactic anticoagulation (i.e., low-dose warfarin) for venous or arterial access devices allowed provided requirements for PT, INR, or PTT are met
• No concurrent cytochrome P450 enzyme-inducing antiepileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
• No concurrent rifampin
• No concurrent Hypericum perforatum (St. John’s wort)