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

This is an interventional treatment trial for Adenocarcinoma of the Bladder Read More

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 =< 1.5 times upper limit of normal (ULN)
• AST or ALT =< 2.5 times ULN
• Creatinine =< 2.5 times ULN OR creatinine clearance => 40 mL/min
• Urine protein: creatinine ratio =< 1 OR 24-hour urine protein < 500 mg
• INR =< 1.5 (unless on full-dose warfarin)
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for >= 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