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

September 25, 2017 updated by: Boehringer Ingelheim

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.

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

125

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Wien, Austria
        • 1199.37.43001 Boehringer Ingelheim Investigational Site
      • Wien, Austria
        • 1199.37.43002 Boehringer Ingelheim Investigational Site
  • France
      • Paris, France
        • 1199.37.33001 Boehringer Ingelheim Investigational Site
      • Paris, France
        • 1199.37.33002 Boehringer Ingelheim Investigational Site
  • Germany
      • Berlin, Germany
        • 1199.37.49008 Boehringer Ingelheim Investigational Site
      • Erlangen, Germany
        • 1199.37.49009 Boehringer Ingelheim Investigational Site
      • Freiburg, Germany
        • 1199.37.49002 Boehringer Ingelheim Investigational Site
      • Hannover, Germany
        • 1199.37.49001 Boehringer Ingelheim Investigational Site
      • Heidelberg, Germany
        • 1199.37.49010 Boehringer Ingelheim Investigational Site
      • Jena, Germany
        • 1199.37.49005 Boehringer Ingelheim Investigational Site
      • Magdeburg, Germany
        • 1199.37.49004 Boehringer Ingelheim Investigational Site
      • München, Germany
        • 1199.37.49003 Boehringer Ingelheim Investigational Site
      • Tübingen, Germany
        • 1199.37.49006 Boehringer Ingelheim Investigational Site
  • Hungary
      • Debrecen, Hungary
        • 1199.37.36001 Boehringer Ingelheim Investigational Site
  • Netherlands
      • Leiden, Netherlands
        • 1199.37.31002 Boehringer Ingelheim Investigational Site
      • Utrecht, Netherlands
        • 1199.37.31001 Boehringer Ingelheim Investigational Site
  • Poland
      • Olsztyn, Poland
        • 1199.37.48002 Boehringer Ingelheim Investigational Site
      • Warsaw, Poland
        • 1199.37.48003 Boehringer Ingelheim Investigational Site
      • Warszawa, Poland
        • 1199.37.48001 Boehringer Ingelheim Investigational Site
  • Romania
      • Bucharest, Romania
        • 1199.37.40002 Boehringer Ingelheim Investigational Site
      • Cluj-Napoca, Romania
        • 1199.37.40003 Boehringer Ingelheim Investigational Site
  • United Kingdom
      • Edgbaston, Birmingham, United Kingdom
        • 1199.37.44001 Boehringer Ingelheim Investigational Site
      • Glasgow, United Kingdom
        • 1199.37.44005 Boehringer Ingelheim Investigational Site
      • Liverpool, United Kingdom
        • 1199.37.44008 Boehringer Ingelheim Investigational Site
      • London, United Kingdom
        • 1199.37.44002 Boehringer Ingelheim Investigational Site
      • London, United Kingdom
        • 1199.37.44003 Boehringer Ingelheim Investigational Site
      • Manchester, United Kingdom
        • 1199.37.44006 Boehringer Ingelheim Investigational Site
      • Nottingham, United Kingdom
        • 1199.37.44004 Boehringer Ingelheim Investigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Sorafenib
Drug: Sorafenib
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose in Phase I
Time Frame: 4 weeks
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
Time to Progression (TTP) in Phase II
Time Frame: From randomization until data cut-off (15 July 2014); Up to 1031 days
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Dose Limiting Toxicity in Phase I
Time Frame: 4 weeks
Number of patients with dose limiting toxicity are presented
4 weeks
Objective Tumour Response by RECIST
Time Frame: From randomization until data cut-off (15 July 2014); Up to 1031 days

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
Progression Free Survival (PFS)
Time Frame: From randomization until data cut-off (15 July 2014); Up to 1031 days
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
Overall Survival
Time Frame: From randomization until data cut-off (15 July 2014); Up to 1031 days
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Boehringer Ingelheim

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 22, 2009

Primary Completion (ACTUAL)

July 14, 2014

Study Completion (ACTUAL)

October 12, 2016

Study Registration Dates

First Submitted

October 12, 2009

First Submitted That Met QC Criteria

October 28, 2009

First Posted (ESTIMATE)

October 29, 2009

Study Record Updates

Last Update Posted (ACTUAL)

October 26, 2017

Last Update Submitted That Met QC Criteria

September 25, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1199.37
  • 2009-011925-14 (EUDRACT_NUMBER: EudraCT)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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