Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-24 @ 5:43 PM
Ignite Modification Date:
2025-12-24 @ 5:43 PM
NCT ID:
NCT00767468
Brief Summary:
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 I trial is studying the side effects and best dose of sorafenib in treating patients with locally advanced or metastatic liver cancer and cirrhosis.
Detailed Description:
OBJECTIVES:
Primary
* To evaluate the pharmacokinetic parameters of sorafenib tosylate in patients with locally advanced or metastatic hepatocellular carcinoma and Child-Pugh B cirrhosis.
* To correlate the pharmacokinetic parameters of sorfenib tosylate with hepatic retention and clearance of technetium Tc 99m mebrofenin (MEB) and technetium Tc 99m sestamibi (MIBI).
Secondary
* To establish a tolerable dose of sorafenib tosylate based on degree of liver dysfunction (bilirubin ≤ 3 times upper limit of normal \[ULN\] or bilirubin \> 3 times but ≤ 6 times ULN).
* To correlate the pharmacokinetics MEB and MIBI with the dose-limiting toxicity of sorafenib tosylate.
* To explore whether increase in bilirubin consists primarily of conjugated or unconjugated bilirubin in response to sorafenib tosylate.
* To explore whether there is a correlation between increased bilirubin and decreased clearance of MEB and/or MIBI.
* To explore whether there is a correlation between survival and MRI characteristics associated with high tumor VEGF levels.
* To assess VEGF levels directly in available biopsy samples using IHC.
* To determine expression levels of hepatic transport proteins (i.e., OATPs, Pgp, or MRPs) that may correlate with clearance of sorafenib tosylate.
* To explore whether there is a correlation between survival and activation of the RAF/MEK/ERK pathway at baseline.
* To estimate median overall survival.
OUTLINE: This is a multicenter study. Patients are stratified according to degree of hepatic dysfunction (moderate \[bilirubin ≤ 3 times upper limit of normal (ULN)\] vs severe \[bilirubin \> 3 times but ≤ 6 times ULN\]).
Patients receive oral sorafenib tosylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Patients undergo hepatic scintigraphy with technetium Tc 99m mebrofinin (MEB) and technetium Tc 99m sestamibi (MIBI) at baseline. Blood and urine samples are collected periodically for pharmacokinetic studies.
After completion of study therapy, patients are followed at 3-4 weeks and then every 3 months thereafter.
Study:
NCT00767468
Study Brief:
Protocol Section:
NCT00767468