Phase I/II Comparison of Efficacy and Safety of BIBF 1120 and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Inclusion criteria

• Histologically or cytologically confirmed diagnosis of hepatocellular carcinoma (HCC) not amenable to curative surgery or loco-regional therapy (RFA, percutaneous ethanol injection (PEI), TACE)
• Age 18 years or older
• Eastern Cooperative Oncology Group performance score of 2 or less
• Child-Pugh score A (score 5-6)
• At least one measurable lesion according to RECIST 1.0 (this criterion is limited to phase II only)
• In case a measurable lesion was previously treated by loco-regional therapy (RFA, PEI, TACE or RT) , this lesion must have to be documented as progression according to RECIST 1.0 by CT or MRI (this criterion is limited to phase II only).
• Time interval from last local therapy (e.g. radiofrequency ablation, percutaneous ethanol injection, radiotherapy, transarterial chemoembolization) more than 4 weeks prior to start of study treatment
• Written informed consent consistent with International Conference on Harmonisation/ Good Clinical Practice (ICH-GCP) and local legislation

Exclusion criteria

• Prior systemic therapy for HCC
• Fibrolamellar hepatocellular carcinoma (HCC)
• Bilirubin greater than 1.5 times ULN
• AST or ALT greater than 2 times ULN
• Uncontrolled or refractory ascites to adequate medical therapy
• Hepatic encephalopathy more than grade 1 according to Child-Pugh criteria
• Prothrombin time international normalized ratio greater than 2.3, or prothrombin time more than 6 seconds prolonged than control
• Absolute neutrophil count less than 1000 /µL
• Platelet count less than 60000 /µL
• Hemoglobin less than 9 g/dL
• Serum creatinine greater than 1.5 times Upper Limit of Normal (ULN)
• Proteinuria of Common Terminology Criteria for Adverse Events (CTCAE) grade 2 or greater
• Variceal bleeding within last 6 months prior to start of study treatment
• History of major thrombotic (except portal vein thrombosis) or clinically relevant major bleeding event in the past 6 months
• Known inherited predisposition to bleeding or thrombosis
• Significant cardiovascular diseases (i.e. hypertension not controlled by medical therapy, blood pressure > 150/90 mmHg), unstable angina, history of myocardial infarction within the past 6 months, congestive heart failure > class II according to New York Heart Association (NYHA), serious cardiac arrhythmia, pericardial effusion)
• Therapeutic anticoagulation (except low dose heparin and/or heparin flush as needed for maintenance of an indwelling intravenous device) or antiplatelet therapy (except for chronic low-dose therapy with acetylsalicylic acid =< 325mg per day)
• Major surgery within 4 weeks prior to start of study treatment
• Treatment with other investigational drugs or participation in another clinical trial within the past four weeks before start of therapy or concomitantly with this trial (except for present trial drug)
• Known serious illness or concomitant non-oncological disease such as neurologic, psychiatric, infectious disease or active ulcers (gastro-intestinal tract, skin) or laboratory abnormality that may increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study
• Patients who are sexually active and unwilling to use a medically acceptable method of contraception (e.g. such as implants, injectables, combined oral contraceptives, some intrauterine devices or vasectomized partner for participating females, condoms for participating males) during the trial and for at least twelve months after end of active therapy
• Current alcohol abuse or drug abuse that would limit pt ability to comply with protocol
• Symptomatic central nervous system (CNS) metastasis
• Life expectancy less than 12 weeks
• Patient unable to take oral medication