Drug Monitoring of Sorafenib in Patients With Advanced Hepatocellular Carcinoma (DOSE-HEP)

Inclusion Criteria:

• ECOG ≤ 2
• Histologically or cytologically diagnosed hepatocellular carcinoma, or diagnosis on at least one cross-sectional imaging with the characteristic appearance of HCC (i.e. liver lesion with arterial enhancement and portal venous washout)
• Decision to treat with single agent sorafenib at 400mg bid (dose reductions or interruptions are permitted if side effects occur during treatment)
• No prior systemic chemotherapy or targeted therapy
• Child-Pugh liver function class A or B
• At least one untreated target lesion that can be measured in one dimension according to RECIST
• Adequate organ functions

Exclusion Criteria:

• Prior systemic chemotherapy or molecularly targeted therapy
• Concurrent active malignancy
• Concomitant strong CYP3A4 induced or inhibitor at a therapeutic dose (see section 6.4.1)
• Medical or psychiatric conditions that compromise the patient's ability to give informed consent
• Hypertension that cannot be controlled by medications (> 150/100 mmHg despite optimal medical therapy)
• History of, or known brain metastases (skull metastases allowed), carcinomatous meningitis, or leptomenigeal disease
• Major surgery (e.g. open abdominal therapy, pelvic, thoracic, orthopaedic or neurosurgery) within 4 weeks of the date of first dose
• Local-regional treatment (i.e. percutaneous and trans-arterial procedures) within 4 weeks. Restaging CT or MRI scan must be repeated at least 4 weeks after local-regional treatment and within 3 weeks before the date of first dose
• For patients treated with Yttrium (90Y) radiotherapy, a washout period of 2 months is required.
• Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the investigator's opinion makes it undesirable for the patient to participate in the study or which would jeopardize compliance with the protocol
• Pregnancy or breast feeding