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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01004003
First received: October 12, 2009
Last updated: August 25, 2015
Last verified: August 2015
  Purpose

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


Condition Intervention Phase
Carcinoma, Hepatocellular
Drug: Sorafenib
Drug: BIBF 1120
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Maximum Tolerated Dose in Phase I [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    The MTD was defined as the highest dose studied for which the incidence of DLTs was 0/3 or less than 2/6 patients during the first treatment course.

  • Time to Progression (TTP) in Phase II [ Time Frame: From randomization until data cut-off (15 July 2014); Up to 1031 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Incidence of Dose Limiting Toxicity in Phase I [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    Number of patients with dose limiting toxicity are presented

  • Objective Tumour Response by RECIST [ Time Frame: From randomization until data cut-off (15 July 2014); Up to 1031 days ] [ Designated as safety issue: No ]

    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.


  • Progression Free Survival (PFS) [ Time Frame: From randomization until data cut-off (15 July 2014); Up to 1031 days ] [ Designated as safety issue: No ]
    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.

  • Overall Survival [ Time Frame: From randomization until data cut-off (15 July 2014); Up to 1031 days ] [ Designated as safety issue: No ]
    Overall survival was defined as the duration from date of randomisation to the date of death.


Enrollment: 125
Study Start Date: October 2009
Estimated Study Completion Date: October 2015
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BIBF 1120
Phase I dose escalation and phase II using dose determined in phase I ( 200 mg BID)
Drug: BIBF 1120
Dose escalated in phase I until MTD or adjusted by investigator, dose in phase II part based on phase I data
Active Comparator: Sorafenib Drug: Sorafenib

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • Histologically or cytologically confirmed diagnosis of hepatocellular carcinoma (HCC) not amenable tocurative surgery or loco-regional therapy (RFA, 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 carcinmoa (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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01004003

Locations
Austria
1199.37.43001 Boehringer Ingelheim Investigational Site
Wien, Austria
1199.37.43002 Boehringer Ingelheim Investigational Site
Wien, Austria
France
1199.37.33001 Boehringer Ingelheim Investigational Site
Paris, France
1199.37.33002 Boehringer Ingelheim Investigational Site
Paris, France
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, Germany
Hungary
1199.37.36001 Boehringer Ingelheim Investigational Site
Debrecen, Hungary
Netherlands
1199.37.31002 Boehringer Ingelheim Investigational Site
Leiden, Netherlands
1199.37.31001 Boehringer Ingelheim Investigational Site
Utrecht, Netherlands
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, Poland
Romania
1199.37.40002 Boehringer Ingelheim Investigational Site
Bucharest, Romania
1199.37.40003 Boehringer Ingelheim Investigational Site
Cluj-Napoca, Romania
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, United Kingdom
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided

Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01004003     History of Changes
Other Study ID Numbers: 1199.37, 2009-011925-14
Study First Received: October 12, 2009
Results First Received: July 9, 2015
Last Updated: August 25, 2015
Health Authority: Austria: Medicines and Medical Devices Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Netherlands: Central Committee Research Involving Human Subjects
Poland: Registration Medicinal Product Medical Device Biocidal Product
Romania: National Medicines Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Adenocarcinoma
Digestive System Diseases
Digestive System Neoplasms
Liver Diseases
Liver Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Nintedanib
Sorafenib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on September 01, 2015