BIBW 2992 (Afatinib) in Head & Neck Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00514943
First received: August 9, 2007
Last updated: September 30, 2014
Last verified: September 2014
Results First Received: August 8, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Head and Neck Neoplasms
Carcinoma, Squamous Cell
Interventions: Drug: BIBW 2992
Drug: Cetuximab

  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
Open-label randomized, cross-over study. 124 patients were randomised. 3 patients were not treated, 1 in Afatinib arm and 2 in Cetuximab arm.

Reporting Groups
  Description
Afatinib 50 mg / Cetuximab 250mg/m2 Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
Cetuximab 250 mg/m2 / Afatinib 50 mg Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2

Participant Flow for 2 periods

Period 1:   Stage 1
    Afatinib 50 mg / Cetuximab 250mg/m2     Cetuximab 250 mg/m2 / Afatinib 50 mg  
STARTED     62 [1]   62 [2]
COMPLETED     32     36  
NOT COMPLETED     30     26  
Progressive disease                 4                 8  
Other Adverse Event                 16                 6  
Not treated                 1                 2  
Patient refused to continue study meds                 8                 3  
Other than stated above                 1                 7  
[1] 1 randomized patient was not treated
[2] 2 randomized patients were not treated

Period 2:   Stage 2
    Afatinib 50 mg / Cetuximab 250mg/m2     Cetuximab 250 mg/m2 / Afatinib 50 mg  
STARTED     32     36  
COMPLETED     0     0  
NOT COMPLETED     32     36  
Progressive disease                 27                 24  
Other Adverse Event                 3                 10  
Patient refused to continue study meds                 2                 0  
Other than stated above                 0                 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.
No text entered.

Reporting Groups
  Description
Afatinib 50 mg / Cetuximab 250mg/m2 Patients were randomized to Afatinib monotherapy 50mg once daily (q.d.) in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Cetuximab 250 mg/m2 given as 400mg/m2 once in the first week (load) followed by 250mg/m2 weekly thereafter in Stage 2.
Cetuximab 250 mg/m2 / Afatinib 50 mg Patients were randomized to Cetuximab 250 mg/m2 received 400mg/m2 once in the first week followed by 250 mg/m2 weekly thereafter in Stage 1 and if the patients had disease progression or intolerable AEs were crossed over to Afatinib 50 mg once daily (q.d.) for Stage 2
Total Total of all reporting groups

Baseline Measures
    Afatinib 50 mg / Cetuximab 250mg/m2     Cetuximab 250 mg/m2 / Afatinib 50 mg     Total  
Number of Participants  
[units: participants]
  62     62     124  
Age  
[units: years]
Mean ± Standard Deviation
  57.9  ± 9.4     58.8  ± 8.7     58.3  ± 9.0  
Gender  
[units: Number of participants]
     
Female     7     10     17  
Male     55     52     107  
Study-Specific Measure  
[units: Number of participants]
     
Yes     42     41     83  
No     20     21     41  
Study-Specific Measure [1]
[units: millimeters]
Mean ± Standard Deviation
  71.4  ± 44.6     65.4  ± 44.2     68.4  ± 44.3  
[1] Baseline measures were available for only 61 patients in the Afatinib/Cetuximab group and only 60 patients in the Cetuximab/Afatinib group



  Outcome Measures
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1.  Primary:   Tumor Shrinkage Before Crossover (Stage 1) of the Trial as Per Investigator Assessment   [ Time Frame: From randomization until start of Stage 2 treatment, or within 28 days after the termination of Stage 1. ]

2.  Secondary:   Tumor Shrinkage After Crossover (Stage 2) as Per Investigator Assessments   [ Time Frame: From baseline assessed prior to first dose of Stage 2 study medication to 28 days after termination of Stage 2 treatment. ]

3.  Secondary:   Best RECIST Assessment as Per Investigator Assessment for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).   [ Time Frame: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment ]

4.  Secondary:   Best RECIST Assessment as Per ICR for Stage 1 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment).   [ Time Frame: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment ]

5.  Secondary:   Best RECIST Assessment as Per Investigator Assessment for Stage 2 (as as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)   [ Time Frame: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment ]

6.  Secondary:   Best RECIST Assessment as Per ICR for Stage2 (as Confirmed Disease Control (Clinical Benefit) and Objective Response Are Simply Categories of RECIST Assessment)   [ Time Frame: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment ]

7.  Secondary:   Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 1   [ Time Frame: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment ]

8.  Secondary:   Best RECIST Assessment as Onset of Confirmed Objective Response as as Per ICR for Stage 1   [ Time Frame: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment ]

9.  Secondary:   Best RECIST Assessment as Onset of Confirmed Objective Response as Per Investigator Assessment for Stage 2   [ Time Frame: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment ]

10.  Secondary:   Best RECIST Assessment as Confirmed Duration of Objective Response and Disease Control as Per Investigator Assessment for Stage 1   [ Time Frame: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment ]

11.  Secondary:   Best RECIST Assessment as Confirmed Duration of Confirmed Objective Response and Disease Control as Per ICR for Stage 1   [ Time Frame: Response determined from randomization until patient started Stage 2 or within 28 days after termination of Stage 1 treatment ]

12.  Secondary:   Best RECIST Assessment as Confirmed Duration of Objective Response and Disease Control as Per Investigator Assessment for Stage 2   [ Time Frame: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment ]

13.  Secondary:   Best RECIST Assessment as Confirmed Duration of Disease Control as Per ICR for Stage 2   [ Time Frame: Response determined during Stage 2 or within 28 days after termination of Stage 2 treatment ]

14.  Secondary:   Progression Free Survival (PFS) Before Crossover Based on Investigator Assessment   [ Time Frame: From randomisation to disease progression in Stage 1 or death whichever occurred first before crossover. ]

15.  Secondary:   Progression Free Survival (PFS) After Crossover Based on Investigator Assessment   [ Time Frame: From first administration of study medication after cross over to disease progression in Stage 2 or death whichever came first after crossover. ]

16.  Secondary:   Overall Survival (OS)   [ Time Frame: From randomisation to data cut-off date. ]

17.  Secondary:   Time to Deterioration in HRQoL - Stage 1   [ Time Frame: From randomisation to deterioration in HRQoL scores before crossover. ]

18.  Secondary:   Patients With AEs Resulting in Diarrhea, Skin Rash, Dose Reduction, Treatment Discontinuation and Decreased Cardiac Left Ventricular Function   [ Time Frame: First administration of trial medication until 28 days after last drug administration ]

19.  Secondary:   Incidence and Intensity of Adverse Events With Grading According CTCAE   [ Time Frame: First administration of trial medication until 28 days after last drug administration ]

20.  Secondary:   Pre-dose Concentration of Afatinib in Plasma for Dose 40mg and 50mg at Steady State on Day 15 (Cpre,ss,15)   [ Time Frame: Day 15 ]

21.  Secondary:   Pre-dose Concentration of Afatinib in Plasma for Dose 40mg and 50mg at Steady State on Day 29 (Cpre,ss,29)   [ Time Frame: Day 29 ]

22.  Secondary:   Pre-dose Concentration of Afatinib in Plasma for Dose 40mg and 50mg at Steady State on Day 57 (Cpre,ss, 57)   [ Time Frame: Day 57 ]


  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: NCT00514943     History of Changes
Other Study ID Numbers: 1200.28, 2008-007097-38
Study First Received: August 9, 2007
Results First Received: August 8, 2013
Last Updated: September 30, 2014
Health Authority: Belgium: Federal Service Public Health, Food Chain Safety and Environment
France: Agence Francaise de Securite Sanitaire des Produits de Sante
Spain: Spanish Agency of Medicines
United States: Food and Drug Administration