VEGF Trap in Treating Patients With Recurrent, Locally Advanced, or Metastatic Cancer of the Urothelium
Condition: Adenocarcinoma of the Bladder; Distal Urethral Cancer; Metastatic Transitional Cell Cancer of the Renal Pelvis and Ureter; Proximal Urethral Cancer; Recurrent Bladder Cancer; Recurrent Transitional Cell Cancer of the Renal Pelvis and Ureter; Recurrent Urethral Cancer; Squamous Cell Carcinoma of the Bladder; Stage III Bladder Cancer; Stage III Urethral Cancer; Stage IV Bladder Cancer; Transitional Cell Carcinoma of the Bladder; Urethral Cancer Associated With Invasive Bladder Cancer
MeSH terms: Carcinoma; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell; Urethral Neoplasms; Kidney Neoplasms; Ureteral Neoplasms; Recurrence
Intervention: ziv-aflibercept; pharmacological study
Intervention description: Given IV; Correlative studies
Intervention MeSH terms: Aflibercept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying the side effects and how well VEGF Trap works in treating
      patients with recurrent, locally advanced, or metastatic cancer of the urothelium. VEGF Trap
      may stop the growth of tumor cells by blocking blood flow to the tumor.
    

Eligibility criteria:

        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