1. To optimize sorafenib treatment in patients with HCC and CP-B liver cirrhosis by exploration of sorafenib exposure, its variability and predictive factors .Secondary:2. To assess the relation between sorafenib exposure and both toxicity and…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Hepatobiliary neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Exposure and intra- and inter-patient variability in exposure to sorafenib
and its metabolites
2. Identification of predictive factors for sorafenib exposure, i.e. bilirubin,
CYP3A4 activity
Secondary outcome
3. Correlation between sorafenib exposure and adverse events and progression
free survival
4. Difference in exposure to 5 CYP probe drugs following administration of an
oral cocktail of these agents after 4 weeks of sorafenib treatment in
comparison with exposure to these cocktail probe drugs before initiation of
sorafenib (substudy in 15 patients)
Background summary
Sorafenib has proven efficacy in advanced hepatocellular carcinoma (HCC). Most
patients with HCC have impaired liver function due to underlying liver
cirrhosis. The severity of liver cirrhosis might have implications on sorafenib
metabolism. To date, no data showing unequivocal activity and tolerability of
sorafenib in patients with moderate cirrhosis (Child-Pugh (CP)-B) have been
published.
To specifically address this issue, this study aims to explore population
pharmacokinetics of sorafenib and to explore the relationship between sorafenib
exposure and its efficacy and toxicity in CP-B patients with irresectable HCC.
Study objective
1. To optimize sorafenib treatment in patients with HCC and CP-B liver
cirrhosis by exploration of sorafenib exposure, its variability and predictive
factors .
Secondary:
2. To assess the relation between sorafenib exposure and both toxicity and
efficacy
3. To assess possible interaction between sorafenib and other CYP enzyme
activity
Study design
This is a prospective, open-label, national, multicenter observational study to
investigate the tolerability, pharmacokinetics and clinical activity of
sorafenib and its metabolites in patients with HCC and CP-B liver cirrhosis
Intervention
-
Study burden and risks
Enrolled patients will be admitted in the hospital for tree 8h visits for
pharmacokinetic (PK) sampling of sorafenib and midazolam or the drug cocktail
(used for CYP phenotyping). All PK blood samples will be drawn via an
intravenous catheter. The total amount of blood taken will be ca 70 ml. The
risks of these procedures are low.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
advanced hepatocelllar carcinoma (HCC) - BCLC stage C
Child Pugh(CP)-B liver cirrhosis (CP-B score 7 or 8)
Exclusion criteria
Child Pugh-B9 liver cirrhosis
Child Pugh-C liver cirrhosis
Concurrent antitumoral treatment for HCC or other malignancies
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL48419.018.14 |