Status:
TERMINATED
Sorafenib PK in Patients With Advanced HCC and Child-Pugh B
Lead Sponsor:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Collaborating Sponsors:
Erasmus Medical Center
Conditions:
BCLC Stage C HCC
CP-B Liver Cirrhosis
Eligibility:
All Genders
18+ years
Phase:
PHASE2
Brief 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 h...
Detailed Description
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 ...
Eligibility Criteria
Inclusion
- Male or female, 18 years of age or older
- Diagnosis of HCC: diagnosis based on the following criteria:
- 1 radiologic technique: Focal lesion \>1 cm with arterial hypervascularization in 4-phase CT or dynamic contrast enhanced MRI OR
- 2 coincidental dynamic radiologic techniques (CT or MRI) in case one imaging technique is non-conclusive and lesion \> 1 cm OR
- biopsy proven HCC
- Patients with advanced HCC - BCLC stage C
- Cancer related symptoms (symptomatic tumors, ECOG Performance status 1-2), macrovascular invasion (either segmental or portal invasion) or extrahepatic spread (lymph node involvement or distant metastases)
- Not eligible for TACE (; i.e. diffuse tumors, tumors larger than 5 cm)
- Not eligible for curative resection or RFA
- Patients with CP-B liver cirrhosis (CP-B score 7 or 8)
- Capable of giving written informed consent
- History of organ transplant (including prior liver transplantation) is allowed
- HIV, congenital immune defect, any immunosuppressive therapy for autoimmune disease (rheumatoid arthritis) is allowed
Exclusion
- Subjects will not be enrolled in the study if any of the following criteria apply:
- CP-B9 liver cirrhosis
- CP-C liver cirrhosis
- Mental conditions rendering the subject incapable to understand the nature, scope, and consequences of the trial
- Concurrent antitumoral treatment for HCC or other malignancies
- Not eligible for sorafenib treatment
- Bilirubin \> 51 micromol/L
- If female, pregnant or breast feeding (females of child-bearing potential must use adequate contraception and must have a negative pregnancy test performed within 7 days prior to inclusion into this study)
- If male, not using adequate birth control measures
- One or more of the following: - WBC \<2,500 cells/mm3, - ANC \<1,500 cells/mm3, - platelets \<50,000/mm3,
- ECOG performance status \>2
- Patients with known GFR \<30 mL/min/1.73m2
- Significant cardiovascular disease; e.g., myocardial infarction within 6 months of inclusion, chronic heart failure (New York Heart Association class III or IV), unstable coronary artery disease
- Uncontrolled hypertension i.e. systolic blood pressure \> 150 mm Hg and/or diastolic blood pressure \> 90 mm Hg despite optimal medical management (2 classes of antihypertensive drugs)
- History of hemorrhage / bleeding events of grade 3 or worse within 30 days before inclusion into this study
- Previous variceal bleeding within the past 3 months
- Additional exclusion criteria for cocktail test
- Consumption of grapefruit or grapefruit juice and/or kumquats, pummelos, exotic citrus fruit (i.e., star fruit, bitter melon) or grapefruit hybrids from seven days prior to the first dose of cocktail.
- Use of herbal medicine or medication that induce or inhibit CYP3A4/5, CYP2C9, CYP2D6, CYP1A2 and CYP2C19
- Use of omeprazole, warfarin, metoprolol, caffeine or midazolam (=medication of the probe cocktail)
- Concurrent anticoagulant therapy
Key Trial Info
Start Date :
May 1 2014
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
March 1 2017
Estimated Enrollment :
5 Patients enrolled
Trial Details
Trial ID
NCT04051853
Start Date
May 1 2014
End Date
March 1 2017
Last Update
August 21 2019
Active Locations (1)
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1
Academic Medical Center
Amsterdam, Netherlands, 1105 AZ