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Sorafenib PK in Patients With Advanced HCC and Child-Pugh B

NCT04051853 · Status: TERMINATED · Phase: PHASE2 · Type: INTERVENTIONAL · Enrollment: 5

Last updated 2019-08-21

No results posted yet for this study

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.

Conditions

  • BCLC Stage C HCC
  • CP-B Liver Cirrhosis

Interventions

DRUG

Sorafenib

Patients will receive sorafenib at a starting dose of 200 mg twice daily. In the absence of toxicity dosage will be gradually escalated up to 400 mg BID.

OTHER

Midazolam clearance test

Before start of treatment patients receive a single oral dose of midazolam to phenotype CYP3A4 activity. Blood samples will be taken at several time points to measure sorafenib and midazolam concentrations.

OTHER

CYP cocktail clearance test

In a subgroup of 15 patients (in the Academic Medical Center Amsterdam), this test will be replaced by an oral cocktail of subclinical doses of caffeine, midazolam, omeprazole, warfarin and metoprolol and will be repeated after 4 weeks of treatment to assess the influence of sorafenib on cytochrome P450 (CYP) 1A2, 3A4, 2C19, 2C9 and 2D6 activity, respectively.

Sponsors & Collaborators

  • Erasmus Medical Center

    collaborator OTHER

  • Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

    lead OTHER

Principal Investigators

  • Heinz-Josef Klümpen, MD PhD · Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  • Ferry ALM Eskens, MD PhD · Erasmus MC Cancer Institute, Rotterdam

  • R. Bart Takkenberg, MD PhD · Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  • Ron Mathot, PharmD PhD · Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

  • Hans Romijn, MD PhD · Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study Design

Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2014-05-31
Primary Completion
2017-03-31
Completion
2017-03-31

Countries

  • Netherlands

Study Locations

More Related Trials

Entities

Drugs
Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT04051853 on ClinicalTrials.gov