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