Histologically or cytologically confirmed hepatocellular carcinoma not amenable to local therapy with adequate renal, hematological and liver paramenters with Child-Pugh score 7 or less, in 1st line systemic therapy. Note for phase II only liver function group I patients with Child Pugh A will be enrolled MedDRA version: 16.1 Level: LLT Classification code 10049010 Term: Carcinoma hepatocellular Sys
Conditions
Interventions
Product Code: BIBF 1120
Pharmaceutical Form: Capsule, soft
Current Sponsor code: BIBF 1120
Concentration unit: mg milligram(s)
Concentra
Sponsors
Boehringer Ingelheim
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. HCC, either histologically/cytologically confirmed diagnosis or clinically diagnosis by AASLD criteria, which is not amenable to local therapy (RFA, PEI, RT, TACE) 2. Age 18 years or older 3. ECOG performance score of 2 or less 4. Child-Pugh score A (score 5-6) 5. At least one measurable lesion according to RECIST 1.0 (this criterion is limited to phase II only) 6. 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) 7. Time interval from last local therapy more than 4 weeks prior to start of study treatment 8. Written informed consent consistent with ICH-GCP and local legislation Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Prior systemic therapy for metastatic/unresectable HCC (for phase II) 2. More then one line of prior systemic therapy for metastatic/unresectable HCC (for phase I) 3. Fibrolamellar HCC 4. Uncontrolled or refractory ascites by adequate medical therapy 5. Bilirubin greater than 1.5 times ULN 6. AST or ALT greater than 2 times ULN 7. Hepatic encephalopathy more than grade 1 according to Child-Pugh criteria 8. Prothrombin time international normalized ratio greater than 2.3, or prothrombin time more than 6 seconds prolonged than control 9. Absolute neutrophil count less than 1000/µL 10. Platelet count less than 60000/µL 11. Hemoglobin less than 9 g/dL 12. Serum creatinine greater than 1.5 times ULN 13. Proteinuria of CTCAE grade 2 or greater 14. Variceal bleeding within 6 months prior to start of study treatment 15. History of major thrombotic (except portal vein thrombosis) or clinically relevant major bleeding event in the past 6 months 16. Known inherited predisposition to bleeding or thrombosis 17. 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 > NYHA II, serious cardiac arrhythmia, pericardial effusion) 18. 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) 19. Last administration of systemic treatment for HCC within 4 weeks prior to start of study treatment or no recovery from any treatment related toxicity 20. Major surgery within 4 weeks prior to start of study treatment 21. Treatment with other investigational drugs concomitantly with this trial (except for present trial drug) 22. 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 23. 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, condomes for participating males) during the trial and for at least twelve months after end of active therapy 24. Current alcohol abuse or drug abuse that would limit patient ability to comply with protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I part of study: To identify the maximum tolerated dose (MTD) of BIBF 1120 in terms of drug-related adverse events in HCC patients. Phase II of study: To evaluate the efficacy of BIBF 1120 in HCC patients without prior systemic treatment as compared to Sorafenib. ;Secondary Objective: To explore the relationship between pharmacokinetics of BIBF 1120 and liver function assessed by AST, ALT, and bilirubin values as well as by Child-Pugh classification at the study baseline.; Primary end point(s): The primary endpoint of the phase I part is the MTD of BIBF 1120 for HCC patients. The primary endpoint of the phase II part is time-to-progression defined as the time from randomization to disease progression according to RECIST ; Timepoint(s) of evaluation of this end point: May 2011 Apr 2014 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Incidence of DLTs -Objective RECIST 1.0 tumour response -Progression free survival by RECIST 1.0 -Overall survival ;Timepoint(s) of evaluation of this end point: Jul 2014 | — |
Countries
Austria, Germany, Hungary, Netherlands, Slovakia, United Kingdom
Contacts
Public ContactQRPE PSC CT Information Disclosure
Boehringer Ingelheim Pharma GmbH & Co. KG
Outcome results
None listed