Clinical trial NCT01004003: Phase I/II Comparison of Efficacy and Safety of BIBF 1120 and Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Official title: A Multicenter, Open Label, Phase I /Randomised Phase II Study to Evaluate Safety, Pharmacokinetics and Efficacy of BIBF 1120 in Comparison With Oral Sorafenib for Advanced Hepatocellular Carcinoma Patients.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Carcinoma, Hepatocellular
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2009-10-29
Enrollment: 125
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Maximum Tolerated Dose in Phase I
timeFrame: 4 weeks
measure: Time to Progression (TTP) in Phase II
timeFrame: From randomization until data cut-off (15 July 2014); Up to 1031 days
Secondary outcomes:
measure: Incidence of Dose Limiting Toxicity in Phase I
timeFrame: 4 weeks
measure: Objective Tumour Response by RECIST
timeFrame: From randomization until data cut-off (15 July 2014); Up to 1031 days
measure: Progression Free Survival (PFS)
timeFrame: From randomization until data cut-off (15 July 2014); Up to 1031 days
measure: Overall Survival
timeFrame: From randomization until data cut-off (15 July 2014); Up to 1031 days
Other outcomes:
Locations:
city: Wien
country: Austria
facility: 1199.37.43001 Boehringer Ingelheim Investigational Site
city: Wien
country: Austria
facility: 1199.37.43002 Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1199.37.33001 Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1199.37.33002 Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: 1199.37.49008 Boehringer Ingelheim Investigational Site
city: Erlangen
country: Germany
facility: 1199.37.49009 Boehringer Ingelheim Investigational Site
city: Freiburg
country: Germany
facility: 1199.37.49002 Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: 1199.37.49001 Boehringer Ingelheim Investigational Site
city: Heidelberg
country: Germany
facility: 1199.37.49010 Boehringer Ingelheim Investigational Site
city: Jena
country: Germany
facility: 1199.37.49005 Boehringer Ingelheim Investigational Site
city: Magdeburg
country: Germany
facility: 1199.37.49004 Boehringer Ingelheim Investigational Site
city: München
country: Germany
facility: 1199.37.49003 Boehringer Ingelheim Investigational Site
city: Tübingen
country: Germany
facility: 1199.37.49006 Boehringer Ingelheim Investigational Site
city: Debrecen
country: Hungary
facility: 1199.37.36001 Boehringer Ingelheim Investigational Site
city: Leiden
country: Netherlands
facility: 1199.37.31002 Boehringer Ingelheim Investigational Site
city: Utrecht
country: Netherlands
facility: 1199.37.31001 Boehringer Ingelheim Investigational Site
city: Olsztyn
country: Poland
facility: 1199.37.48002 Boehringer Ingelheim Investigational Site
city: Warsaw
country: Poland
facility: 1199.37.48003 Boehringer Ingelheim Investigational Site
city: Warszawa
country: Poland
facility: 1199.37.48001 Boehringer Ingelheim Investigational Site
city: Bucharest
country: Romania
facility: 1199.37.40002 Boehringer Ingelheim Investigational Site
city: Cluj-Napoca
country: Romania
facility: 1199.37.40003 Boehringer Ingelheim Investigational Site
city: Edgbaston, Birmingham
country: United Kingdom
facility: 1199.37.44001 Boehringer Ingelheim Investigational Site
city: Glasgow
country: United Kingdom
facility: 1199.37.44005 Boehringer Ingelheim Investigational Site
city: Liverpool
country: United Kingdom
facility: 1199.37.44008 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1199.37.44002 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1199.37.44003 Boehringer Ingelheim Investigational Site
city: Manchester
country: United Kingdom
facility: 1199.37.44006 Boehringer Ingelheim Investigational Site
city: Nottingham
country: United Kingdom
facility: 1199.37.44004 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References: