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

Carcinoma, Hepatocellular Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01004003
• Other study ID #: 1199.37
• Secondary ID: 2009-011925-14
• Status: Completed
• Phase: Phase 2
• First received: October 12, 2009
• Last updated: September 25, 2017
• Start date: October 22, 2009
• Est. completion date: October 12, 2016

Study information

• Verified date: September 2017
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 125
• Est. completion date: October 12, 2016
• Est. primary completion date: July 14, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• Sorafenib

• BIBF 1120
Dose escalated in phase I until MTD or adjusted by investigator, dose in phase II part based on phase I data

Locations

Country	Name	City	State
Austria	1199.37.43001 Boehringer Ingelheim Investigational Site	Wien
Austria	1199.37.43002 Boehringer Ingelheim Investigational Site	Wien
France	1199.37.33001 Boehringer Ingelheim Investigational Site	Paris
France	1199.37.33002 Boehringer Ingelheim Investigational Site	Paris
Germany	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
Germany	1199.37.49001 Boehringer Ingelheim Investigational Site	Hannover
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
Hungary	1199.37.36001 Boehringer Ingelheim Investigational Site	Debrecen
Netherlands	1199.37.31002 Boehringer Ingelheim Investigational Site	Leiden
Netherlands	1199.37.31001 Boehringer Ingelheim Investigational Site	Utrecht
Poland	1199.37.48002 Boehringer Ingelheim Investigational Site	Olsztyn
Poland	1199.37.48003 Boehringer Ingelheim Investigational Site	Warsaw
Poland	1199.37.48001 Boehringer Ingelheim Investigational Site	Warszawa
Romania	1199.37.40002 Boehringer Ingelheim Investigational Site	Bucharest
Romania	1199.37.40003 Boehringer Ingelheim Investigational Site	Cluj-Napoca
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Austria,  France,  Germany,  Hungary,  Netherlands,  Poland,  Romania,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose in Phase I	The MTD was defined as the highest dose studied for which the incidence of dose limiting toxicities (DLTs) was 0/3 or less than 2/6 patients during the first treatment course.	4 weeks
Primary	Time to Progression (TTP) in Phase II	TTP according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 criteria based on central independent review. TTP RECIST 1.0 was defined as the time from randomisation to disease progression according to RECIST 1.0.	From randomization until data cut-off (15 July 2014); Up to 1031 days
Secondary	Incidence of Dose Limiting Toxicity in Phase I	Number of patients with dose limiting toxicity are presented	4 weeks
Secondary	Objective Tumour Response by RECIST	Objective RECIST 1.0 tumour response was defined as Complete Response (CR) or Partial Response (PR) and was derived from the patient's best objective RECIST 1.0 response based on central independent review.; 95% Confidence Interval presented below are computed by Clopper and Pearson method.	From randomization until data cut-off (15 July 2014); Up to 1031 days
Secondary	Progression Free Survival (PFS)	PFS by RECIST 1.0 was defined as the duration from date of randomisation to date of progression or death, whichever occurred earlier, based on central independent review.	From randomization until data cut-off (15 July 2014); Up to 1031 days
Secondary	Overall Survival	Overall survival was defined as the duration from date of randomisation to the date of death.	From randomization until data cut-off (15 July 2014); Up to 1031 days

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