Phase I/II Comparison of Efficacy and Safety of BIBF 1120 and Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Condition: Carcinoma, Hepatocellular
MeSH terms: Carcinoma; Carcinoma, Hepatocellular
Intervention: Sorafenib; BIBF 1120
Intervention description: Dose escalated in phase I until MTD or adjusted by investigator, dose in phase II part based on phase I data
Intervention MeSH terms: Sorafenib; Nintedanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 125.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The study aim is to determine maximally tolerated dose (MTD) of BIBF 1120 in HCC
      (hepatocellular cancer) and compare efficacy of BIBF 1120 to Sorafenib in HCC patients
    

Eligibility criteria:

        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