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
Results First Received: July 9, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Carcinoma, Hepatocellular
Interventions: Drug: Sorafenib
Drug: BIBF 1120

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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Reporting Groups
  Description
Phase 1 Group 1, 100mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 100 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the maximal tolerated dose (MTD). Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST (aspartate aminotransferase ) and ALT (alanine transaminase) ≤2 times the upper limit of normal (ULN).
Phase I Group 1, 150mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 150 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
Phase I Group 1, 200mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
Phase I Group 2, 50mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 50 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
Phase I Group 2, 100mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 100 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
Phase I Group 2, 150mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 150 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
Phase I Group 2, 200mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
Phase II, 200 mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
Phase II, 400 mg Sorafenib Bid Oral administration of Sorafenib 400 mg film coated tablets twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).

Participant Flow:   Overall Study
    Phase 1 Group 1, 100mg Nintedanib Bid     Phase I Group 1, 150mg Nintedanib Bid     Phase I Group 1, 200mg Nintedanib Bid     Phase I Group 2, 50mg Nintedanib Bid     Phase I Group 2, 100mg Nintedanib Bid     Phase I Group 2, 150mg Nintedanib Bid     Phase I Group 2, 200mg Nintedanib Bid     Phase II, 200 mg Nintedanib Bid     Phase II, 400 mg Sorafenib Bid  
STARTED     6     3     4     3     4     4     8     62     31  
COMPLETED     0     0     0     0     0     0     0     2 [1]   1 [1]
NOT COMPLETED     6     3     4     3     4     4     8     60     30  
Progressive disease                 2                 1                 1                 0                 2                 1                 1                 39                 22  
Adverse Event                 4                 2                 3                 3                 2                 2                 7                 21                 6  
Refused to continue taking trial med.                 0                 0                 0                 0                 0                 0                 0                 0                 2  
Other reason not defined above                 0                 0                 0                 0                 0                 1                 0                 0                 0  
[1] On-treatment at analysis cut-off date (15 July 2014).



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Treated set which included all patients who received at least one single dose of trial medication.

Reporting Groups
  Description
Phase 1 Group 1, 100mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 100 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the maximal tolerated dose (MTD). Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST (aspartate aminotransferase ) and ALT (alanine transaminase) ≤2 times the upper limit of normal (ULN).
Phase I Group 1, 150mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 150 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
Phase I Group 1, 200mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 1 patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
Phase I Group 2, 50mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 50 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
Phase I Group 2, 100mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 100 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
Phase I Group 2, 150mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 150 mg soft gelatine capsules twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
Phase I Group 2, 200mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase I: A standard 3+3 dose escalation part to determine the MTD. Group 2 patients had a baseline Child-Pugh score of 7, or AST or ALT >2 to ≤5 times ULN.
Phase II, 200 mg Nintedanib Bid Oral administration of Nintedanib (BIBF 1120) 200 mg soft gelatine capsules (two capsules of 100mg) twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
Phase II, 400 mg Sorafenib Bid Oral administration of Sorafenib 400 mg film coated tablets twice daily (bid). Phase II: Patients were randomly assigned to open-label treatment with nintedanib or sorafenib. Patients were stratified for macrovascular invasion (MVI) and/or extra-hepatic spread (EHS). Patients had a baseline Child-Pugh score of 5 or 6, and AST and ALT ≤2 times the upper limit of normal (ULN).
Total Total of all reporting groups

Baseline Measures
    Phase 1 Group 1, 100mg Nintedanib Bid     Phase I Group 1, 150mg Nintedanib Bid     Phase I Group 1, 200mg Nintedanib Bid     Phase I Group 2, 50mg Nintedanib Bid     Phase I Group 2, 100mg Nintedanib Bid     Phase I Group 2, 150mg Nintedanib Bid     Phase I Group 2, 200mg Nintedanib Bid     Phase II, 200 mg Nintedanib Bid     Phase II, 400 mg Sorafenib Bid     Total  
Number of Participants  
[units: participants]
  6     3     4     3     4     4     8     62     31     125  
Age  
[units: Years]
Mean (Standard Deviation)
  69.7  (6.8)     65.0  (7.8)     66.5  (4.0)     72.3  (11.7)     56.3  (6.4)     59.3  (13.9)     57.0  (11.0)     65.4  (10.0)     63.1  (11.8)     64.2  (10.5)  
Gender  
[units: Participants]
                   
Female     1     1     0     0     0     1     2     14     5     24  
Male     5     2     4     3     4     3     6     48     26     101  



  Outcome Measures
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1.  Primary:   Maximum Tolerated Dose in Phase I   [ Time Frame: 4 weeks ]

2.  Primary:   Time to Progression (TTP) in Phase II   [ Time Frame: From randomization until data cut-off (15 July 2014); Up to 1031 days ]

3.  Secondary:   Incidence of Dose Limiting Toxicity in Phase I   [ Time Frame: 4 weeks ]

4.  Secondary:   Objective Tumour Response by RECIST   [ Time Frame: From randomization until data cut-off (15 July 2014); Up to 1031 days ]

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

6.  Secondary:   Overall Survival   [ Time Frame: From randomization until data cut-off (15 July 2014); Up to 1031 days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Boehringer Ingelheim Call Center
Organization: Boehringer Ingelheim
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


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