A Randomized Double-Blinded Phase III Study Comparing Gemcitabine, Cisplatin, and Bevacizumab to Gemcitabine, Cisplatin, and Placebo in Patients With Advanced Transitional Cell Carcinoma

Inclusion Criteria:

- Patients must have histologically or cytologically documented metastatic or
unresectable transitional cell (urothelial) carcinoma of the urinary tract (renal
pelvis, ureter, bladder, prostate, or urethra), with metastatic or locally advanced
disease (T4b, N2, N3, or M1); patients must not be candidates for potentially
curative surgery or radiotherapy

- Patients may not have received prior combination systemic chemotherapy for metastatic
disease

- For the purposes of this study, radiosensitizing single-agent chemotherapy is
not considered prior systemic therapy

- Prior neoadjuvant or adjuvant systemic chemotherapy is permissible provided it
was completed >= 1 year prior to the diagnosis of metastatic disease

- At least 4 weeks since prior radiation (including palliative) or major surgery and
fully recovered

- At least 7 days since any minor surgery such as port placement

- At least 4 weeks since any intravesical therapy

- No prior treatment with bevacizumab or other angiogenesis inhibitors

- No known history of brain metastases; brain imaging (magnetic resonance imaging
[MRI]/computed tomography [CT]) is not required

- No current congestive heart failure; New York Heart Association (NYHA) class II, III
or IV

- Patients with history of hypertension must be well controlled (< 150/90) on a regimen
of anti-hypertensive therapy

- Patients on full-dose anticoagulants must be on a stable dose of warfarin and have an
in-range international normalized ratio (INR) (usually between 2 and 3) or be on a
stable dose of low molecular weight (LMW) heparin; patients receiving anti-platelet
agents are also eligible; in addition, patients who are on daily prophylactic aspirin
or anticoagulation for atrial fibrillation are eligible

- No significant history of bleeding events or gastrointestinal (GI) perforation

- Patients with a history of a significant bleeding episode (e.g. hemoptysis,
upper or lower GI bleeding, grade 3 or 4 gross hematuria unable to be controlled
by trans-urethral resection of the bladder tumor) within 6 months of
registration are not eligible

- Patients with a history of GI perforation within 12 months of registration are
not eligible

- Patients with a history of peritoneal carcinomatosis are not eligible

- No arterial thrombotic events within 6 months of registration, including transient
ischemic attack (TIA), cerebrovascular accident (CVA), peripheral arterial thrombus,
unstable angina or angina requiring surgical or medical intervention in the past 6
months, or myocardial infarction (MI); patients with clinically significant
peripheral artery disease (i.e., claudication on less than one block) are ineligible

- Patients who have experienced a deep venous thrombosis or pulmonary embolus within
the past 6 months must be on stable therapeutic anticoagulation to be enrolled to
this study

- No serious or non-healing wound, ulcer, or bone fracture

- No sensory or motor peripheral neuropathy >= grade 2

- Patients with known hypersensitivity to Chinese hamster ovary cell products or other
recombinant human antibodies are not eligible

- Patients that are pregnant or nursing are not eligible; women of child bearing
potential must have a negative serum or urine pregnancy test (minimum sensitivity 25
IU/L or equivalent units of human chorionic gonadotropin [HCG]) within 72 hours prior
to registration

- For women of child-bearing potential with an elevated beta-HCG that is believed
to be related to cancer and not pregnancy, a negative trans-vaginal ultrasound
and gynecological examination are required

- Women of child-bearing potential include any female who has experienced menarche
and who has not undergone surgical sterilization (hysterectomy, bilateral tubal
ligation or bilateral oophorectomy) or is not postmenopausal [defined as
amenorrhea >= 12 consecutive months; or women on hormone replacement therapy
[HRT] with documented serum follicle stimulating hormone [FSH] level >
35mIU/mL); even women who are using oral, implanted or injectable contraceptive
hormones or mechanical products such as an intrauterine device or barrier
methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing
abstinence or where partner is sterile (e.g., vasectomy), should be considered
to be of child bearing potential

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 OR Karnofsky PS
>= 80

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Calculated or measured creatinine clearance >= 50 mL/minute

- Bilirubin =< 1.25 times upper limit of normal (ULN) (for patients with Gilbert's
Disease, =< 2.5 X ULN is allowed)

- Aspartate aminotransferase (AST) =< 2.0 times ULN

- Urine protein to creatinine ratio < 1.0 OR urine protein =< 1+ OR 24-hour urine
protein =< 1 gram