Trial of BIBW 2992 (Afatinib) + Cetuximab in Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT01090011
First received: March 10, 2010
Last updated: June 20, 2014
Last verified: June 2014
Results First Received: January 9, 2014  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Carcinoma, Non-Small-Cell Lung
Interventions: Drug: Cetuximab
Drug: BIBW 2992

  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
Enrolled:201 Entered and treated:171

Reporting Groups
  Description
Total All patients entered and treated. The objective of this study was to determine the maximum tolerated dose of Afatinib using a "3+3 Up-and-Down" trial design. Cohorts of three to six participants were entered (not randomized) sequentially into escalating dosage tiers of afatinib/cetuximab. The dose of cetuximab in successive cohorts was increased unless two or more of the six participants (of the current cohort) had dose limiting toxicity events.

Participant Flow:   Overall Study
    Total  
STARTED     171  
COMPLETED     20  
NOT COMPLETED     151  
Progressive disease                 114  
Adverse Event                 29  
Protocol Violation                 1  
Refusal to start/continue medication                 5  
Other reason not found above                 2  



  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

Reporting Groups
  Description
Total Patients All patients entered and treated. The objective of this study was to determine the maximum tolerated dose of Afatinib using a "3+3 Up-and-Down" trial design. Cohorts of three to six participants were entered (not randomized) sequentially into escalating dosage tiers of afatinib/cetuximab. The dose of cetuximab in successive cohorts was increased unless two or more of the six participants (of the current cohort) had dose limiting toxicity events.

Baseline Measures
    Total Patients  
Number of Participants  
[units: participants]
  171  
Age  
[units: years]
Mean ± Standard Deviation
  58.1  ± 10.5  
Gender  
[units: participants]
 
Female     119  
Male     52  



  Outcome Measures
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1.  Primary:   The Primary Endpoint is the Occurrence of Dose Limiting Toxicity (DLT).   [ Time Frame: from day 1 treatment until progression or undue toxicity, up to 28 days ]

2.  Secondary:   Highest CTCAE Grade   [ Time Frame: From Informed Consent Form to 28 days after discontinuation of drug intake up to 915 days ]

3.  Secondary:   Frequency of Patients [N(%)] With Possible Clinically Significant Abnormalities for Selected Laboratory Parameters   [ Time Frame: From Informed Consent Form to 28 days after discontinuation of drug intake up to 915 days ]

4.  Secondary:   Frequency (%) of Patients With Adverse Events Leading to Dose Reduction   [ Time Frame: From Informed Consent Form to 28 days after discontinuation of drug intake up to 915 days ]

5.  Secondary:   Frequency (%) of Patients With Adverse Events Leading to Treatment Discontinuation   [ Time Frame: From Informed Consent Form to 28 days after discontinuation of drug intake up to 915 days ]

6.  Secondary:   Frequency (%) of Patients With Adverse Events Leading to Death   [ Time Frame: From Informed Consent Form to 28 days after discontinuation of drug intake up to 915 days ]

7.  Secondary:   Frequency (%) of Patients With Related Serious Adverse Events   [ Time Frame: From Informed Consent Form to 28 days after discontinuation of drug intake up to 915 days ]

8.  Secondary:   Area Under the Concentration-time Curve (AUC) on Day 15 of Plasma Afatinib for the Combination Arm   [ Time Frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 ]

9.  Secondary:   Concentration of Afatinib in Plasma for the Combination Arm   [ Time Frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 ]

10.  Secondary:   Peak-trough Fluctuation (PTF)   [ Time Frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 ]

11.  Secondary:   t1/2,ss   [ Time Frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 ]

12.  Secondary:   MRTpo,ss   [ Time Frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 ]

13.  Secondary:   CL/F,ss,15   [ Time Frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 ]

14.  Secondary:   Vz/F,ss   [ Time Frame: Course 1, Visit 3 and 4, Day 15 and 16, Hours: -0:05,0,1,2,3,4,5,6,8, and 23:55 ]

15.  Secondary:   Predose Plasma Concentrations of Afatinib for the Combination Arm   [ Time Frame: Up to 57 days ]

16.  Secondary:   Disease Control (CR, PR and Stable Disease (SD) Determined by RECIST v1.1)   [ Time Frame: up to 116 weeks ]

17.  Secondary:   Objective Tumor Response (Complete Response [CR] and Partial Response [PR]) Determined by RECIST v1.1)   [ Time Frame: up to 116 weeks ]

18.  Secondary:   Duration of Objective Response (According to RECIST v1.1)   [ Time Frame: up to 116 weeks ]

19.  Secondary:   Duration of Disease Control (According to RECIST v1.1)   [ Time Frame: up to 116 weeks ]

20.  Secondary:   Progression-Free Survival (PFS) Time   [ Time Frame: up to 116 weeks ]


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


No publications provided


Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01090011     History of Changes
Other Study ID Numbers: 1200.71, 2009-015911-42
Study First Received: March 10, 2010
Results First Received: January 9, 2014
Last Updated: June 20, 2014
Health Authority: Netherlands: Central Committee Research Involving Human Subjects
United States: Food and Drug Administration