Sorafenib in Treating Patients With Metastatic or Unresectable Kidney Cancer
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor.
PURPOSE: This phase II trial is studying the side effects and how well sorafenib works in treating patients with metastatic or unresectable kidney cancer.
Drug: sorafenib tosylate
Other: flow cytometry
Other: laboratory biomarker analysis
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Sorafenib in Patients With Metastatic Renal Cell Carcinoma|
- Toxicity of intrapatient dose escalation of sorafenib tosylate [ Time Frame: Study completion ] [ Designated as safety issue: Yes ]To evaluate the toxicity of dose escalating sorafenib, an estimation of the percentage of patients who are unable to tolerate those escalated doses will be made. Patients will be dose escalated every 4 weeks until a maximum dose of 800 mg BID is reached.
- Response Rate [ Time Frame: from the start of the treatment until disease progression/recurrence ] [ Designated as safety issue: No ]The proportion of subjects with an objective response of complete or partial based on the RECIST Criteria
- Time to progression [ Time Frame: from the start of study treatment to disease progression or death ] [ Designated as safety issue: No ]Time to progression survival will be defined as the number of days from the day the subject was consented to the day the subject experiences an event of disease progression, or to the date of death if disease progression is not reached.
- Overall survival [ Time Frame: From start of study treatment until death ] [ Designated as safety issue: No ]Time to death for a given subject will be defined as the number of days from the day the subject was consented to the date of the subject's death.
|Study Start Date:||March 2007|
|Estimated Study Completion Date:||January 2015|
|Primary Completion Date:||October 2009 (Final data collection date for primary outcome measure)|
Drug: sorafenib tosylate
initial dose of Sorafenib will be administered orally with a dose of 400 mg twice a day, daily.Intrapatient dose escalation will occur providing no dose limiting toxicity (Grade 3 or 4) is observed. Dose level 2 600mg. Dose level 2 800mgOther: flow cytometry
15 ml of blood drawn for flow cytometry of T4/T8, NK, CD25+, and Fox p3 testing obtained at baseline and on days 28, 56, 84, and 112Other: laboratory biomarker analysis
15 ml of plasma and urine for storage and future determination of VEGF concentration will be obtained at baseline.10 ml of plasma and urine for storage and future determination of VEGF concentration will be obtained on days 28, 56, 84 and 112
- Evaluate the safety and toxicity of dose escalating sorafenib tosylate in patients with metastatic or unresectable renal cell carcinoma.
- Determine tumor response in these patients.
- Determine time to progression in these patients.
- Determine overall survival of these patients.
- Collect data on angiogenesis inhibition induced by sorafenib tosylate.
- Collect data on immunomodulatory effects of sorafenib tosylate.
OUTLINE: This is an open-label study.
Patients receive oral sorafenib tosylate twice daily on days 1-28. Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.
Patients receive escalating doses of sorafenib tosylate (in the absence of grade 3 or 4 dose-limiting toxicity) until a pre-determined dose is reached.
Blood and urine samples are collected at baseline and periodically during study for VEGF level determination. Blood samples are analyzed for T4/T8, NK, CD25+, and Fox p3 by flow cytometry. Tumor tissue blocks or unstained slides are obtained for chemistry staining of VEGF.
|United States, Nebraska|
|UNMC Eppley Cancer Center at the University of Nebraska Medical Center|
|Omaha, Nebraska, United States, 68198-6805|
|Principal Investigator:||Ralph Hauke, MD||University of Nebraska|