Phase II Trial of Gemcitabine, Carboplatin, and Bevacizumab in Chemotherapy Naive Patients With Advanced/Metastatic Urothelial Carcinoma

Inclusion Criteria:

- Histologic documentation: diagnosis of transitional cell carcinoma of the
bladder,urethra, ureter, or renal pelvis.

- Unresectable or metastatic disease

- Ineligible for cisplatin (or incurable with cisplatin)

- ≥ 4 weeks since prior RT

- Karnofsky Performance Status ≥ 60%

- Age ≥ 18 years of age

- Required Initial Laboratory Values: Absolute neutrophil count ≥ 1.2 x 109/L;
Platelets ≥ 100 x 109/L; Bilirubin ≤ 1.5 times the upper limit of normal (x ULN) for
the institution; Aspartate transaminase (AST) and alanine transaminase(ALT) ≤ 3.0 x
ULN;Serum creatinine < 2.0 or calculated creatinine clearance (CrCl) ≥ 30 mL/min

Exclusion Criteria:

- Prior treatment with systemic chemotherapy (prior intravesical therapy is permitted)

- Current, recent (within 4 weeks of the first infusion of this study), or planned
participation in an experimental drug study other than a Genentech-sponsored
bevacizumab cancer study

- Blood pressure of >150/100 mmHg

- Unstable angina

- New York Heart Association (NYHA) Grade II or greater congestive heart failure

- History of myocardial infarction within 6 months

- History of stroke within 6 months

- Clinically significant peripheral vascular disease

- Evidence of bleeding diathesis or coagulopathy

- Presence of central nervous system or brain metastases

- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
prior to Day 0

- Anticipation of need for major surgical procedure during the course of the study

- Minor surgical procedures such as fine needle aspirations or core biopsies within 7
days prior to Day 0

- Pregnant (positive pregnancy test) or lactating

- Albuminuria as demonstrated by a urinary albumin of greater or = to 1.0 g/24 hr at
screening

- History of abdominal fistula, gastrointestinal perforation, or intra abdominal
abscess within 6 months prior to Day 0

- Serious, non-healing wound, ulcer, or bone fracture

- Inability to comply with study and/or follow-up procedures

- History of persistent gross hematuria