Gemcitabine and Split-dose Cisplatin (GC) Plus Sorafenib in Chemotherapy-naïve Patients With Locally Advanced or Metastatic Urothelial Carcinoma

Inclusion Criteria:

• Patients must have measurable or evaluable urothelial cancer.

  • Measurable disease includes unresectable or metastatic urothelial tract tumors that are unidimensionally measurable by xray,CT/MRI scan or physical examination.
  • Evaluable disease is restricted to patients with unresectable primary bladder tumors which can be evaluated for response by cystoscopy.
• Pathologic confirmation by the Department of Pathology at MSKCC.
• Karnofsky Performance Status (KPS) ≥60%.
• Adequate marrow function defined as granulocytes ≥ 1500 cells/mm 3 , platelets ≥ 100,000 cells/mm 3 , and hemoglobin ≥ 8.0 g/dl.
• Serum creatinine < 2.0 mg/dl
• 24-hour urine sample demonstrating creatinine clearance ≥ 60 ml/min/1.73m2 or calculated creatinine clearance ≥ 60 ml/min/1.73m 2 using the formula: Jeliffe Equation: estimated creatinine clearance = 98 x (0.8 [age(yrs) 20]/Serum Creatinine (mg/dL) x (0.9 if Female))

• Adequate hepatic function defined as:

  • Total Bilirubin < or = to 1.5 x ULN
  • AST and ALT < or = to 3.0 x ULN (< or = to 5.0 x ULN is acceptable if liver has tumor involvement)
• Normal coagulation profile including PT/INR and PTT, unless patient is receiving anticoagulation therapy with agents such as warfarin or heparin.
• Age ≥ 18 years
• Informed consent
• Women of childbearing potential must have a negative pregnancy test.
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.
• Patients are encouraged to continue barrier method contraception for two years or longer after treatment.

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.
• Blood Pressure of > 150/100 mm Hg.
• Irradiation within 4 weeks of start of protocol.
• Evidence of another active cancer, except for nonmelanoma skin carcinoma, insitu carcinoma of the cervix curatively treated, and adenocarcinoma of the prostate that has been surgically treated with a post-treatment PSA that is nondetectable.
• Significant cardiovascular disease including congestive heart failure (New York Heart Association Class II or higher) or active angina pectoris.
• History of a myocardial infarction within 6 months.
• History of a stroke or transient ischemic attack 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.
• Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to Day 0.
• History of abdominal fistula, gastrointestinal perforation, or intraabdominal abscess within 6 months prior to Day 0.
• Serious nonhealing wound, ulcer, or bone fracture.
• History of persistent gross hematuria.
• Uncontrolled infection.
• Hypersensitivity to sorafenib, or any component of the formulation.
• Pregnant (positive pregnancy test) or lactating.
• Inability to comply with the study and/or followup procedures.