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

NCT ID: NCT01004003

Last Updated: 2017-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 125 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-22
• Study Completion Date: 2016-10-12

Brief 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

Conditions

Carcinoma, Hepatocellular

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BIBF 1120

Phase I dose escalation and phase II using dose determined in phase I ( 200 mg BID)

Group Type: EXPERIMENTAL

BIBF 1120

Intervention Type: DRUG

Dose escalated in phase I until MTD or adjusted by investigator, dose in phase II part based on phase I data

Sorafenib

Group Type: ACTIVE_COMPARATOR

Sorafenib

Intervention Type: DRUG

Interventions

Sorafenib

Intervention Type: DRUG

BIBF 1120

Dose escalated in phase I until MTD or adjusted by investigator, dose in phase II part based on phase I data

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

1199.37.43001 Boehringer Ingelheim Investigational Site

Vienna, , Austria

1199.37.43002 Boehringer Ingelheim Investigational Site

Vienna, , Austria

1199.37.33001 Boehringer Ingelheim Investigational Site

Paris, , France

1199.37.33002 Boehringer Ingelheim Investigational Site

Paris, , France

1199.37.49008 Boehringer Ingelheim Investigational Site

Berlin, , Germany

1199.37.49009 Boehringer Ingelheim Investigational Site

Erlangen, , Germany

1199.37.49002 Boehringer Ingelheim Investigational Site

Freiburg im Breisgau, , Germany

1199.37.49001 Boehringer Ingelheim Investigational Site

Hanover, , Germany

1199.37.49010 Boehringer Ingelheim Investigational Site

Heidelberg, , Germany

1199.37.49005 Boehringer Ingelheim Investigational Site

Jena, , Germany

1199.37.49004 Boehringer Ingelheim Investigational Site

Magdeburg, , Germany

1199.37.49003 Boehringer Ingelheim Investigational Site

München, , Germany

1199.37.49006 Boehringer Ingelheim Investigational Site

Tübingen, , Germany

1199.37.36001 Boehringer Ingelheim Investigational Site

Debrecen, , Hungary

1199.37.31002 Boehringer Ingelheim Investigational Site

Leiden, , Netherlands

1199.37.31001 Boehringer Ingelheim Investigational Site

Utrecht, , Netherlands

1199.37.48002 Boehringer Ingelheim Investigational Site

Olsztyn, , Poland

1199.37.48001 Boehringer Ingelheim Investigational Site

Warsaw, , Poland

1199.37.48003 Boehringer Ingelheim Investigational Site

Warsaw, , Poland

1199.37.40002 Boehringer Ingelheim Investigational Site

Bucharest, , Romania

1199.37.40003 Boehringer Ingelheim Investigational Site

Cluj-Napoca, , Romania

1199.37.44001 Boehringer Ingelheim Investigational Site

Edgbaston, Birmingham, , United Kingdom

1199.37.44005 Boehringer Ingelheim Investigational Site

Glasgow, , United Kingdom

1199.37.44008 Boehringer Ingelheim Investigational Site

Liverpool, , United Kingdom

1199.37.44002 Boehringer Ingelheim Investigational Site

London, , United Kingdom

1199.37.44003 Boehringer Ingelheim Investigational Site

London, , United Kingdom

1199.37.44006 Boehringer Ingelheim Investigational Site

Manchester, , United Kingdom

1199.37.44004 Boehringer Ingelheim Investigational Site

Nottingham, , United Kingdom

Countries

Slovakia; Austria; France; Germany; Hungary; Netherlands; Poland; Romania; United Kingdom

Other Identifiers

2009-011925-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1199.37

Identifier Type: -

Identifier Source: org_study_id