Trial of Gemcitabine, Carboplatin, and Sorafenib in Chemotherapy-naive Patients With Advanced/Metastatic Bladder Carcinoma

Inclusion Criteria

• Histologic documentation of diagnosis of transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis
• Unresectable, locally advanced or metastatic disease
• CrCl ≥ 60 ml/min or serum creatinine 9.0 g/dl
• Absolute neutrophil count (ANC) ≥ 1,500/mm3
• Platelet count ≥ 100,000/mm3
• Total bilirubin ≤ 1.5 times ULN
• ALT and AST ≤ 2.5 times the ULN ( ≤ 5 x ULN for patients with liver involvement)
• INR 12 months have lapsed)
• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study
• Cardiac disease: Congestive heart failure > class II NYHA. Patients must not have unstable angina (anginal symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months.
• History of stroke within six months
• Clinically significant peripheral vascular disease
• Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
• Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.
• Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic pressure > 90 mmHg, despite optimal medical management.
• Sorafenib is contraindicated in patients with known severe hypersensitivity to sorafenib or any of the excipients.
• Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.
• Active clinically serious infection > CTCAE Grade 2.
• Thrombolytic or embolic events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months
• Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of study drug
• Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of study drug
• Evidence or history of bleeding diathesis or coagulopathy
• Major surgery, significant traumatic injury within 4 weeks of first study drug
• Use of St. John's Wort or rifampin (rifampicin)
• Known or suspected allergy to sorafenib or any agent given in the course of this trial
• Any condition that impairs patient's ability to swallow whole pills
• Any malabsorption problem
• Anticipation of need for major surgical procedure during the course of the study
• Pregnant (positive pregnancy test) or lactating
• 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