Phase I Dose Escalation Study of Concomitant BIBF 1120 and BIBW 2992 in Patients With Advanced Solid Tumours.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00998296
First received: October 19, 2009
Last updated: February 6, 2015
Last verified: February 2015
Results First Received: November 14, 2014  
Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Neoplasms
Interventions: Drug: BIBW 2992
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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Results are based on the primary analysis.

Reporting Groups
  Description
Nintedanib 150 mg +Afatinib 30 mg - Continuously Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.)
Nintedanib 150 mg +Afatinib 40 mg - Continuously Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.)
Nintedanib 200 mg +Afatinib 10 mg - Continuously Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 10 mg was given continuously once daily (q.d.)
Nintedanib 200 mg +Afatinib 20 mg - Continuously Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 20 mg was given continuously once daily (q.d.)
Nintedanib 200 mg +Afatinib 30 mg - Continuously Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.)
Nintedanib 200 mg +Afatinib 40 mg - Continuously Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.)
Nintedanib 150 mg +Afatinib 40 mg - Intermittently Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week
Nintedanib 200 mg +Afatinib 30 mg - Intermittently Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given intermittently once daily (q.d.) every other week
Nintedanib 200 mg +Afatinib 40 mg - Intermittently Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week

Participant Flow:   Overall Study
    Nintedanib 150 mg +Afatinib 30 mg - Continuously     Nintedanib 150 mg +Afatinib 40 mg - Continuously     Nintedanib 200 mg +Afatinib 10 mg - Continuously     Nintedanib 200 mg +Afatinib 20 mg - Continuously     Nintedanib 200 mg +Afatinib 30 mg - Continuously     Nintedanib 200 mg +Afatinib 40 mg - Continuously     Nintedanib 150 mg +Afatinib 40 mg - Intermittently     Nintedanib 200 mg +Afatinib 30 mg - Intermittently     Nintedanib 200 mg +Afatinib 40 mg - Intermittently  
STARTED     6     3     3     3     8     3     7     6     6  
COMPLETED     6 [1]   2 [1]   3 [1]   3 [1]   6 [1]   3 [1]   6 [1]   4 [1]   4 [1]
NOT COMPLETED     0     1     0     0     2     0     1     2     2  
Progressive disease                 0                 1                 0                 0                 0                 0                 1                 0                 0  
Dose limiting or dose reducing toxicity                 0                 0                 0                 0                 1                 0                 0                 2                 2  
Other adverse event                 0                 0                 0                 0                 1                 0                 0                 0                 0  
[1] Did not discontinue treatment before or at Day 28



  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 (TS): A treated set (TS) was defined consisting of all patients who received at least one dose of nintedanib or afatinib during the study period.

Reporting Groups
  Description
Nintedanib 150 mg +Afatinib 30 mg - Continuously Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.)
Nintedanib 150 mg +Afatinib 40 mg - Continuously Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.)
Nintedanib 200 mg +Afatinib 10 mg - Continuously Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 10 mg was given continuously once daily (q.d.)
Nintedanib 200 mg +Afatinib 20 mg - Continuously Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 20 mg was given continuously once daily (q.d.)
Nintedanib 200 mg +Afatinib 30 mg - Continuously Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given continuously once daily (q.d.)
Nintedanib 200 mg +Afatinib 40 mg - Continuously Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given continuously once daily (q.d.)
Nintedanib 150 mg +Afatinib 40 mg - Intermittently Patients receiving oral administration of soft-gelatine capsule of Nintedanib 150 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week
Nintedanib 200 mg +Afatinib 30 mg - Intermittently Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 30 mg was given intermittently once daily (q.d.) every other week
Nintedanib 200 mg +Afatinib 40 mg - Intermittently Patients receiving oral administration of soft-gelatine capsule of Nintedanib 200 mg continuously twice daily (b.i.d.); concomitantly, film-coated tablet of Afatinib 40 mg was given intermittently once daily (q.d.) every other week
Total Total of all reporting groups

Baseline Measures
    Nintedanib 150 mg +Afatinib 30 mg - Continuously     Nintedanib 150 mg +Afatinib 40 mg - Continuously     Nintedanib 200 mg +Afatinib 10 mg - Continuously     Nintedanib 200 mg +Afatinib 20 mg - Continuously     Nintedanib 200 mg +Afatinib 30 mg - Continuously     Nintedanib 200 mg +Afatinib 40 mg - Continuously     Nintedanib 150 mg +Afatinib 40 mg - Intermittently     Nintedanib 200 mg +Afatinib 30 mg - Intermittently     Nintedanib 200 mg +Afatinib 40 mg - Intermittently     Total  
Number of Participants  
[units: participants]
  6     3     3     3     8     3     7     6     6     45  
Age  
[units: years]
Mean (Standard Deviation)
  53.7  (8.1)     51.7  (1.5)     46.7  (4.9)     53.3  (11.0)     51.5  (9.7)     44.3  (8.1)     64.9  (3.5)     52.2  (6.0)     63.3  (10.3)     54.9  (9.6)  
Gender  
[units: participants]
                   
Female     3     1     0     1     6     2     0     4     2     19  
Male     3     2     3     2     2     1     7     2     4     26  



  Outcome Measures
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1.  Primary:   Maximum Tolerated Dose (MTD) of Nintedanib and Afatinib Based on the Percentage of Participants Experienced Dose Limiting Toxicities   [ Time Frame: first treatment cycle, up to 28 days ]

2.  Secondary:   Overall Tumour Response Rate Assessed by the Investigator According to the Response Evaluation Criteria In Solid Tumours (RECIST) Version 1.1   [ Time Frame: Week 6 ]

3.  Secondary:   Incidence and Intensity of Adverse Events According to CTCAE (Common Toxicity Criteria Adverse Event) Version 3.0   [ Time Frame: First treatment administration until cut-off date of 16 November 2012 up to 267 days ]

4.  Secondary:   Changes in Safety Laboratory Parameters   [ Time Frame: First treatment administration until cut-off date of 16 November 2012, up to 267 days ]

5.  Secondary:   Cpre,ss,Norm (Dose Normalized Trough Plasma Concentration of Nintedanib at Steady State)   [ Time Frame: Day 8, Day 15, Day 22 and Day 28 ]

6.  Secondary:   Trough Plasma Concentration of Afatinib at Steady State   [ Time Frame: Day 7, Day 13, Day 15, Day 22, Day 27 and Day 28 ]


  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
Statistics of PK parameters are only estimated when at least 2/3 of the data are evaluable.


  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 Pharmaceuticals
phone: 1-800-243-0127
e-mail: clintriage.rdg@boehringer-ingelheim.com


No publications provided


Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00998296     History of Changes
Other Study ID Numbers: 1239.14, 2009-011321-14
Study First Received: October 19, 2009
Results First Received: November 14, 2014
Last Updated: February 6, 2015
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
United States: Food and Drug Administration