VEGF Trap in Treating Patients With Recurrent, Locally Advanced, or Metastatic Cancer of the Urothelium

Inclusion Criteria

• Histologically confirmed transitional cell carcinoma (TCC) of the urothelium
• Must have predominance of transitional histology, but foci of squamous and/or adenocarcinoma histology allowed
• Poorly differentiated transitional cell carcinoma allowed
• TCC of any of the following sites allowed:
• Bladder
• Renal pelvis
• Ureter
• Urethra
• Measurable disease, defined as >= 1 unidimensionally measurable lesion >= 20 mm by conventional techniques OR >= 10 mm by spiral CT scan
• Locoregionally advanced or metastatic disease that is not amenable to curative surgery and/or radiotherapy
• Must have received 1 prior systemic chemotherapy regimen containing a platinum compound (e.g., cisplatin, carboplatin, or oxaliplatin) in the neoadjuvant, adjuvant, or metastatic setting
• No evidence of CNS disease, including primary brain tumor or brain metastases
• ECOG performance status 0-2
• Absolute neutrophil count >= 1,000/mm^3
• Platelet count >= 75,000/mm^3
• Bilirubin = 40 mL/min
• Urine protein: creatinine ratio = = 6 months after completion of study treatment
• No known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
• No history of allergic reactions attributed to compounds of similar chemical or biological composition to other agents used in the study
• No serious or nonhealing wound, ulcer, or bone fracture
• No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
• No significant traumatic injury within the past 28 days
• No clinically significant cardiovascular disease, including any of the following:
• Myocardial infarction, coronary artery bypass graft, or unstable angina pectoris within the past 6 months
• New York Heart Association class III or IV congestive heart failure
• Serious cardiac arrhythmia requiring medication
• Clinically significant peripheral vascular disease within the past 6 months
• Cerebrovascular accident within the past 6 months
• Pulmonary embolism, deep vein thrombosis, or other thromboembolic event within the past 6 months
• Uncontrolled hypertension, defined as blood pressure (BP) > 150/100 mm Hg or systolic BP > 180 mm Hg (if diastolic BP < 90 mm Hg) within the past 3 months
• No evidence of bleeding diathesis or coagulopathy
• No uncontrolled intercurrent illness, including, but not limited to, any of the following:
• Ongoing or active infection
• Psychiatric illness or social situation that would preclude study compliance
• Recovered from prior therapy
• Prior biologic or targeted therapies allowed
• No more than 1 prior systemic chemotherapy regimen for metastatic disease
• No prior antiangiogenic therapy primarily targeting the vascular endothelial growth factor pathway
• At least 4 weeks since prior radiotherapy or systemic therapy (6 weeks for mitomycin C or nitrosoureas)
• More than 28 days since prior major surgery or open biopsy
• More than 7 days since prior core biopsy
• No concurrent major surgery
• Concurrent full-dose anticoagulants (e.g., warfarin) allowed provided all of the following criteria are met:
• In-range INR (usually between 2 and 3) on a stable dose of oral anticoagulant or low molecular weight heparin
• No active bleeding or pathological condition that carries a high risk of bleeding (e.g., tumor involving major vessels or known varices)
• No other concurrent investigational agents
• No concurrent combination antiretroviral therapy for HIV-positive patients