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LUX-Head&Neck 2: A Phase III Trial of Afatinib (BIBW 2992) Versus Placebo for the Treatment of Head and Neck Squamous Cell Cancer After Treatment With Chemo-radiotherapy

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ClinicalTrials.gov Identifier: NCT01345669
Recruitment Status : Terminated
First Posted : May 2, 2011
Results First Posted : October 23, 2017
Last Update Posted : December 7, 2017
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double;   Primary Purpose: Treatment
Condition Head and Neck Neoplasms
Interventions Drug: Placebo
Drug: Afatinib
Enrollment 617
Recruitment Details  
Pre-assignment Details This was a randomised, placebo-controlled, double-blind, parallel arms, multinational phase III trial in which patients were randomised 2:1 to Afatinib or Placebo.
Arm/Group Title Afatinib (BIBW 2992) Placebo
Hide Arm/Group Description Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Period Title: Overall Study
Started 411 206
Completed 124 87
Not Completed 287 119
Reason Not Completed
Primary tumour recurrence             53             32
Second primary tumour             4             3
Adverse Event             63             9
Protocol Violation             3             1
Lost to Follow-up             1             1
Withdrawal by Subject             52             13
Other Reasons             111             60
Arm/Group Title Afatinib (BIBW 2992) Placebo Total
Hide Arm/Group Description Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. Total of all reporting groups
Overall Number of Baseline Participants 411 206 617
Hide Baseline Analysis Population Description
Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 411 participants 206 participants 617 participants
58.3  (8.23) 57.3  (8.64) 58.0  (8.38)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 411 participants 206 participants 617 participants
Female
61
  14.8%
28
  13.6%
89
  14.4%
Male
350
  85.2%
178
  86.4%
528
  85.6%
1.Primary Outcome
Title Disease Free Survival (DFS)
Hide Description Disease Free Survival defined as the time from randomisation until documented tumour recurrence/ second primary tumour (SPT) or death from any cause, whichever occurred first.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised)
Arm/Group Title Afatinib (BIBW 2992) Placebo
Hide Arm/Group Description:
Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 411 206
Median (Inter-Quartile Range)
Unit of Measure: Months
43.40 [1] 
(16.82 to NA)
NA [2] 
(16.69 to NA)
[1]
Non calculable because the 75th percentile hasn't been reached
[2]
Non calculable because the median hasn't been reached
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Placebo
Comments DFS was analysed using a stratified log-rank test with nodal status (N0- N2a vs. N2b-N3) and Eastern Cooperative Oncology Group (ECOG) performance status (0 vs. 1) being the stratification factors.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4806
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.126
Confidence Interval (2-Sided) 95%
0.809 to 1.569
Estimation Comments Hazard ratio (Afatinib vs. Placebo) from Cox proportional hazards model stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).
2.Secondary Outcome
Title Disease Free Survival (DFS) Rate at 2 Years
Hide Description Disease Free Survival (DFS) rate at 2 years. Probability of being disease free at 2 years in percentage is provided based on Kaplan-Meier method.
Time Frame Up to 2 years
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set, the number of patients from the randomized set those are disease free (or DFS) at 2 years.
Arm/Group Title Afatinib (BIBW 2992) Placebo
Hide Arm/Group Description:
Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 117 76
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Probability (%)
67.2
(61.2 to 72.5)
73.5
(66.0 to 79.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Placebo
Comments Kaplan-Meier (KM) curves were calculated for each treatment group, separately, and the estimates of DFS probabilities from the curves and 95% Confidence interval (CI) (using the Greenwood standard error estimate) were tabulated
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1610
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in Kaplan-Meier estimates
Estimated Value -6.27
Confidence Interval (2-Sided) 95%
-15.04 to 2.50
Estimation Comments Difference in Kaplan-Meier estimates of Afatinib vs. Placebo is provided.
3.Secondary Outcome
Title Percentage of Patient Deaths (Overall Survival (OS))
Hide Description Overall survival (OS), defined as the time from randomisation until death (regardless of cause). Due to the small event rate in both treatment arms caused by the early termination of the trial, the hazard estimate is not interpretable. Hence presented the total randomized and the percentage of patients died.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised)
Arm/Group Title Afatinib (BIBW 2992) Placebo
Hide Arm/Group Description:
Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 411 206
Measure Type: Number
Unit of Measure: Percentage of patients
15.1 11.2
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Placebo
Comments Hazard ratio from Cox proportional hazards model stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1301
Comments p-value (two-sided) from log-rank test stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.444
Confidence Interval (2-Sided) 95%
0.895 to 2.332
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Patients With Improved Health Related Quality of Life (HRQOL)
Hide Description HRQoL questionnaires focused on 3 scales: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Improvement was defined as a score that improved from baseline by at least 10 points (on the 0-100 point scale) at any time during the study. If a patient had not improved, worsening was defined as a 10-point worsening at any time during the study. Patients who had neither improved nor worsened were considered as stable. Percentages of patients with improvement in HRQoL are presented.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised)
Arm/Group Title Afatinib (BIBW 2992) Placebo
Hide Arm/Group Description:
Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 411 206
Measure Type: Number
Unit of Measure: Percentage of Patients
Swallowing (Q5-Q8 from QLQ-HN35) 34.8 27.2
Pain HN35 (Q1-Q4 from QLQ-HN35) 33.8 26.2
Global health status/QoL(Q29-Q30 from QLQ-C30) 33.6 38.3
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Placebo
Comments Odds ratio and p-value from logistic regression analysis of 'improved vs. not improved' stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3) for Swallowing (Q5-Q8 from QLQ-HN35).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0561
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.431
Confidence Interval (2-Sided) 95%
0.991 to 2.068
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Placebo
Comments Odds ratio and p-value from logistic regression analysis of 'improved vs. not improved' stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3) for Pain HN35 (Q1-Q4 from QLQ-HN35).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0523
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.446
Confidence Interval (2-Sided) 95%
0.996 to 2.098
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Placebo
Comments Odds ratio and p-value from logistic regression analysis of 'improved vs. not improved' stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3) for Global health status/QoL(Q29-Q30 from QLQ-C30).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2570
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.818
Confidence Interval (2-Sided) 95%
0.577 to 1.158
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time to Deterioration in Health Related Quality of Life (HRQOL)
Hide Description HRQoL questionnaires focused on 3 scales: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Time to deterioration was defined as the time from randomisation to the first 10-point worsening on the 0-100 point scale. Patients with no deterioration (including those with disease recurrence/SPT) were censored at the last available HRQoL assessment date. Patients with no post-baseline assessments were censored on the day of randomisation.
Time Frame Up to 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised)
Arm/Group Title Afatinib (BIBW 2992) Placebo
Hide Arm/Group Description:
Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 411 206
Median (Inter-Quartile Range)
Unit of Measure: Months
Swallowing
18.43 [1] 
(3.68 to NA)
31.44 [1] 
(3.78 to NA)
Pain HN35
12.06 [1] 
(1.91 to NA)
31.08 [1] 
(3.78 to NA)
Global health status/QoL
7.59 [1] 
(1.87 to NA)
25.79 [1] 
(6.21 to NA)
[1]
Non calculable because the 75th percentile hasn't been reached
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Placebo
Comments For swallowing scale; Hazard ratio from Cox proportional hazard model stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0591
Comments P-value from log-rank test stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.295
Confidence Interval (2-Sided) 95%
0.986 to 1.700
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Placebo
Comments For pain HN35 scale; Hazard ratio from Cox proportional hazard model stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0049
Comments P-value from log-rank test stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.456
Confidence Interval (2-Sided) 95%
1.113 to 1.905
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Placebo
Comments For global health status/QoL scale; Hazard ratio from Cox proportional hazard model stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments P-value from log-rank test stratified by baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.604
Confidence Interval (2-Sided) 95%
1.238 to 2.079
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Health Related Quality of Life (HRQOL) Scores Over Time
Hide Description HRQoL questionnaires focused on 3 scales: Pain scale from H&N35, Swallowing scale from H&N35 and Global health status/QoL scale from C30. Scoring of the symptom scales/items followed the European Organisation for Research and Treatment of Cancer (EORTC) scoring manual and a linear transformation of the scores to a 0-100 point scale. Higher values are better.
Time Frame Baseline and 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set (RS): Included all patients who were randomised, regardless of taking investigational treatment (as randomised)
Arm/Group Title Afatinib (BIBW 2992) Placebo
Hide Arm/Group Description:
Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
Overall Number of Participants Analyzed 411 206
Least Squares Mean (Standard Error)
Unit of Measure: Unit on Scale
Swallowing 10.1  (1.00) 8.8  (1.12)
Pain HN35 13.1  (0.98) 9.9  (1.10)
Global health status/QoL 29.6  (2.23) 33.0  (2.28)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Placebo
Comments Scores (swallowing scale) over time were assessed using longitudinal mixed-effects growth curve models with the average profile over time for each endpoint described by a piecewise linear model adjusted for the fixed effects baseline ECOG performance score and nodal status.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2232
Comments [Not Specified]
Method Mixed Models Analysis
Comments Degrees of freedom calculated using the Kenward-Roger method.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
-0.81 to 3.45
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.08
Estimation Comments Afatinib minus Placebo mean adjusted for total with data for baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Placebo
Comments Scores (pain scale) over time were assessed using longitudinal mixed-effects growth curve models with the average profile over time for each endpoint described by a piecewise linear model adjusted for the fixed effects baseline ECOG performance score and nodal status.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0028
Comments [Not Specified]
Method Mixed Models Analysis
Comments Degrees of freedom calculated using the Kenward-Roger method.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 3.2
Confidence Interval (2-Sided) 95%
1.12 to 5.36
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.08
Estimation Comments Afatinib minus Placebo mean adjusted for total with data for baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Afatinib (BIBW 2992), Placebo
Comments Scores (global health/QoL) over time were assessed using longitudinal mixed-effects growth curve models with the average profile over time for each endpoint described by a piecewise linear model adjusted for the fixed effects baseline ECOG performance score and nodal status.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Mixed Models Analysis
Comments Degrees of freedom calculated using the Kenward-Roger method.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -3.4
Confidence Interval (2-Sided) 95%
-5.33 to -1.49
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.98
Estimation Comments Afatinib minus Placebo mean adjusted for total with data for baseline ECOG (0 or 1) and nodal status (N0-N2a or N2b-N3).
Time Frame From first drug administration until 4 weeks after the last drug administration, up to 84 weeks
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Afatinib (BIBW 2992) Placebo
Hide Arm/Group Description Patient received Afatinib film-coated tablets with starting dose 40 mg (milligram)/day and escalation to 50 mg/day and/or reduction to 40, 30 or 20 mg/day according to absence or presence of drug-related adverse events (AEs), orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal. Patient received placebo matching Afatinib film-coated tablets with matching Afatinib dosage regimen, orally, once daily for up to 80 weeks or until recurrence / occurrence of second primary tumour, unacceptable side effects, or other reason necessitating withdrawal.
All-Cause Mortality
Afatinib (BIBW 2992) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Afatinib (BIBW 2992) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   80/411 (19.46%)   51/206 (24.76%) 
Blood and lymphatic system disorders     
Anaemia  1  4/411 (0.97%)  2/206 (0.97%) 
Cardiac disorders     
Acute coronary syndrome  1  0/411 (0.00%)  1/206 (0.49%) 
Aortic valve stenosis  1  0/411 (0.00%)  1/206 (0.49%) 
Arrhythmia  1  0/411 (0.00%)  2/206 (0.97%) 
Atrial flutter  1  1/411 (0.24%)  0/206 (0.00%) 
Cardiac arrest  1  1/411 (0.24%)  1/206 (0.49%) 
Cardiac failure congestive  1  0/411 (0.00%)  1/206 (0.49%) 
Cardio-respiratory arrest  1  1/411 (0.24%)  0/206 (0.00%) 
Ear and labyrinth disorders     
Deafness neurosensory  1  1/411 (0.24%)  0/206 (0.00%) 
Endocrine disorders     
Inappropriate antidiuretic hormone secretion  1  0/411 (0.00%)  1/206 (0.49%) 
Eye disorders     
Retinal tear  1  1/411 (0.24%)  0/206 (0.00%) 
Gastrointestinal disorders     
Colitis  1  0/411 (0.00%)  1/206 (0.49%) 
Diarrhoea  1  2/411 (0.49%)  0/206 (0.00%) 
Duodenal ulcer haemorrhage  1  1/411 (0.24%)  0/206 (0.00%) 
Dyspepsia  1  1/411 (0.24%)  0/206 (0.00%) 
Dysphagia  1  2/411 (0.49%)  1/206 (0.49%) 
Gastric perforation  1  1/411 (0.24%)  0/206 (0.00%) 
Gastrointestinal haemorrhage  1  1/411 (0.24%)  0/206 (0.00%) 
Glossitis  1  1/411 (0.24%)  0/206 (0.00%) 
Intestinal haemorrhage  1  1/411 (0.24%)  0/206 (0.00%) 
Large intestine polyp  1  0/411 (0.00%)  1/206 (0.49%) 
Melaena  1  1/411 (0.24%)  0/206 (0.00%) 
Nausea  1  1/411 (0.24%)  0/206 (0.00%) 
Oesophagitis  1  0/411 (0.00%)  1/206 (0.49%) 
Pancreatitis  1  1/411 (0.24%)  0/206 (0.00%) 
Pancreatitis acute  1  1/411 (0.24%)  1/206 (0.49%) 
Pancreatitis relapsing  1  1/411 (0.24%)  0/206 (0.00%) 
Stomatitis  1  1/411 (0.24%)  0/206 (0.00%) 
Vomiting  1  1/411 (0.24%)  0/206 (0.00%) 
General disorders     
Asthenia  1  0/411 (0.00%)  1/206 (0.49%) 
Death  1  1/411 (0.24%)  1/206 (0.49%) 
Disease recurrence  1  1/411 (0.24%)  0/206 (0.00%) 
Fatigue  1  0/411 (0.00%)  1/206 (0.49%) 
Impaired healing  1  0/411 (0.00%)  1/206 (0.49%) 
Malaise  1  1/411 (0.24%)  0/206 (0.00%) 
Mucosal inflammation  1  1/411 (0.24%)  0/206 (0.00%) 
Non-cardiac chest pain  1  1/411 (0.24%)  0/206 (0.00%) 
Oedema  1  0/411 (0.00%)  1/206 (0.49%) 
Pyrexia  1  1/411 (0.24%)  0/206 (0.00%) 
Sudden death  1  1/411 (0.24%)  0/206 (0.00%) 
Hepatobiliary disorders     
Bile duct stone  1  1/411 (0.24%)  0/206 (0.00%) 
Cholecystitis  1  1/411 (0.24%)  0/206 (0.00%) 
Cholelithiasis  1  1/411 (0.24%)  0/206 (0.00%) 
Hepatic failure  1  1/411 (0.24%)  0/206 (0.00%) 
Immune system disorders     
Hypersensitivity  1  1/411 (0.24%)  0/206 (0.00%) 
Sarcoidosis  1  0/411 (0.00%)  1/206 (0.49%) 
Infections and infestations     
Appendicitis perforated  1  0/411 (0.00%)  1/206 (0.49%) 
Carbuncle  1  1/411 (0.24%)  0/206 (0.00%) 
Cellulitis  1  2/411 (0.49%)  0/206 (0.00%) 
Cellulitis of male external genital organ  1  1/411 (0.24%)  0/206 (0.00%) 
Diverticulitis  1  0/411 (0.00%)  1/206 (0.49%) 
Erysipelas  1  1/411 (0.24%)  0/206 (0.00%) 
Groin infection  1  1/411 (0.24%)  0/206 (0.00%) 
Hepatitis E  1  0/411 (0.00%)  1/206 (0.49%) 
Infection  1  1/411 (0.24%)  0/206 (0.00%) 
Lung infection  1  1/411 (0.24%)  1/206 (0.49%) 
Oropharyngeal candidiasis  1  1/411 (0.24%)  0/206 (0.00%) 
Osteomyelitis  1  0/411 (0.00%)  1/206 (0.49%) 
Pneumonia  1  1/411 (0.24%)  5/206 (2.43%) 
Respiratory tract infection  1  0/411 (0.00%)  1/206 (0.49%) 
Septic shock  1  1/411 (0.24%)  1/206 (0.49%) 
Upper respiratory tract infection  1  1/411 (0.24%)  0/206 (0.00%) 
Urethritis  1  1/411 (0.24%)  0/206 (0.00%) 
Injury, poisoning and procedural complications     
Accident  1  0/411 (0.00%)  1/206 (0.49%) 
Accidental overdose  1  1/411 (0.24%)  0/206 (0.00%) 
Osteoradionecrosis  1  2/411 (0.49%)  0/206 (0.00%) 
Patella fracture  1  0/411 (0.00%)  1/206 (0.49%) 
Post procedural complication  1  0/411 (0.00%)  1/206 (0.49%) 
Post procedural haemorrhage  1  1/411 (0.24%)  0/206 (0.00%) 
Radiation fibrosis  1  1/411 (0.24%)  0/206 (0.00%) 
Radiation necrosis  1  1/411 (0.24%)  0/206 (0.00%) 
Vascular graft complication  1  0/411 (0.00%)  1/206 (0.49%) 
Investigations     
Aspartate aminotransferase increased  1  1/411 (0.24%)  0/206 (0.00%) 
Blood bilirubin increased  1  1/411 (0.24%)  0/206 (0.00%) 
Electrocardiogram QT prolonged  1  1/411 (0.24%)  0/206 (0.00%) 
Gamma-glutamyltransferase increased  1  1/411 (0.24%)  0/206 (0.00%) 
Weight decreased  1  1/411 (0.24%)  1/206 (0.49%) 
Metabolism and nutrition disorders     
Decreased appetite  1  3/411 (0.73%)  1/206 (0.49%) 
Dehydration  1  1/411 (0.24%)  1/206 (0.49%) 
Hypokalaemia  1  1/411 (0.24%)  0/206 (0.00%) 
Hyponatraemia  1  2/411 (0.49%)  0/206 (0.00%) 
Musculoskeletal and connective tissue disorders     
Groin pain  1  1/411 (0.24%)  0/206 (0.00%) 
Neck pain  1  1/411 (0.24%)  0/206 (0.00%) 
Osteonecrosis  1  0/411 (0.00%)  3/206 (1.46%) 
Osteonecrosis of jaw  1  0/411 (0.00%)  1/206 (0.49%) 
Scleroderma  1  2/411 (0.49%)  1/206 (0.49%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  3/411 (0.73%)  0/206 (0.00%) 
Colon cancer  1  0/411 (0.00%)  1/206 (0.49%) 
Lung neoplasm malignant  1  0/411 (0.00%)  1/206 (0.49%) 
Metastases to lung  1  2/411 (0.49%)  0/206 (0.00%) 
Metastases to lymph nodes  1  0/411 (0.00%)  1/206 (0.49%) 
Neoplasm recurrence  1  5/411 (1.22%)  3/206 (1.46%) 
Oesophageal carcinoma  1  0/411 (0.00%)  1/206 (0.49%) 
Oropharyngeal squamous cell carcinoma  1  2/411 (0.49%)  1/206 (0.49%) 
Recurrent cancer  1  1/411 (0.24%)  0/206 (0.00%) 
Squamous cell carcinoma of skin  1  1/411 (0.24%)  0/206 (0.00%) 
Nervous system disorders     
Carotid artery thrombosis  1  1/411 (0.24%)  0/206 (0.00%) 
Cerebrovascular accident  1  2/411 (0.49%)  0/206 (0.00%) 
Ischaemic stroke  1  1/411 (0.24%)  1/206 (0.49%) 
Migraine  1  1/411 (0.24%)  0/206 (0.00%) 
Partial seizures with secondary generalisation  1  1/411 (0.24%)  0/206 (0.00%) 
Presyncope  1  0/411 (0.00%)  1/206 (0.49%) 
Sciatica  1  0/411 (0.00%)  1/206 (0.49%) 
Spinal cord compression  1  1/411 (0.24%)  0/206 (0.00%) 
Syncope  1  0/411 (0.00%)  1/206 (0.49%) 
Wernicke's encephalopathy  1  1/411 (0.24%)  0/206 (0.00%) 
Product Issues     
Device occlusion  1  1/411 (0.24%)  0/206 (0.00%) 
Renal and urinary disorders     
Acute kidney injury  1  2/411 (0.49%)  0/206 (0.00%) 
Renal failure  1  1/411 (0.24%)  0/206 (0.00%) 
Renal impairment  1  1/411 (0.24%)  0/206 (0.00%) 
Urinary retention  1  0/411 (0.00%)  1/206 (0.49%) 
Reproductive system and breast disorders     
Balanoposthitis  1  1/411 (0.24%)  0/206 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Aspiration  1  1/411 (0.24%)  0/206 (0.00%) 
Cough  1  0/411 (0.00%)  1/206 (0.49%) 
Dyspnoea  1  2/411 (0.49%)  3/206 (1.46%) 
Interstitial lung disease  1  3/411 (0.73%)  0/206 (0.00%) 
Laryngeal dyspnoea  1  0/411 (0.00%)  1/206 (0.49%) 
Laryngeal oedema  1  8/411 (1.95%)  8/206 (3.88%) 
Laryngeal stenosis  1  1/411 (0.24%)  0/206 (0.00%) 
Pneumonitis  1  1/411 (0.24%)  0/206 (0.00%) 
Pneumothorax  1  2/411 (0.49%)  0/206 (0.00%) 
Pneumothorax spontaneous  1  0/411 (0.00%)  1/206 (0.49%) 
Pulmonary alveolar haemorrhage  1  0/411 (0.00%)  1/206 (0.49%) 
Pulmonary hypertension  1  1/411 (0.24%)  0/206 (0.00%) 
Respiratory arrest  1  1/411 (0.24%)  0/206 (0.00%) 
Respiratory failure  1  1/411 (0.24%)  0/206 (0.00%) 
Respiratory tract oedema  1  1/411 (0.24%)  0/206 (0.00%) 
Tracheal stenosis  1  0/411 (0.00%)  1/206 (0.49%) 
Skin and subcutaneous tissue disorders     
Dermatitis exfoliative  1  1/411 (0.24%)  0/206 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  1/411 (0.24%)  0/206 (0.00%) 
Hypotension  1  0/411 (0.00%)  1/206 (0.49%) 
Peripheral ischaemia  1  1/411 (0.24%)  1/206 (0.49%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Afatinib (BIBW 2992) Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   407/411 (99.03%)   169/206 (82.04%) 
Blood and lymphatic system disorders     
Anaemia  1  23/411 (5.60%)  7/206 (3.40%) 
Gastrointestinal disorders     
Abdominal pain  1  21/411 (5.11%)  6/206 (2.91%) 
Cheilitis  1  22/411 (5.35%)  1/206 (0.49%) 
Constipation  1  33/411 (8.03%)  20/206 (9.71%) 
Diarrhoea  1  335/411 (81.51%)  41/206 (19.90%) 
Dry mouth  1  55/411 (13.38%)  25/206 (12.14%) 
Dyspepsia  1  42/411 (10.22%)  10/206 (4.85%) 
Dysphagia  1  48/411 (11.68%)  21/206 (10.19%) 
Gastrooesophageal reflux disease  1  23/411 (5.60%)  2/206 (0.97%) 
Nausea  1  43/411 (10.46%)  24/206 (11.65%) 
Oral pain  1  23/411 (5.60%)  6/206 (2.91%) 
Stomatitis  1  107/411 (26.03%)  12/206 (5.83%) 
Vomiting  1  40/411 (9.73%)  20/206 (9.71%) 
General disorders     
Asthenia  1  43/411 (10.46%)  23/206 (11.17%) 
Fatigue  1  61/411 (14.84%)  21/206 (10.19%) 
Mucosal inflammation  1  126/411 (30.66%)  17/206 (8.25%) 
Pyrexia  1  29/411 (7.06%)  7/206 (3.40%) 
Infections and infestations     
Conjunctivitis  1  21/411 (5.11%)  2/206 (0.97%) 
Nasopharyngitis  1  22/411 (5.35%)  18/206 (8.74%) 
Paronychia  1  85/411 (20.68%)  4/206 (1.94%) 
Upper respiratory tract infection  1  19/411 (4.62%)  15/206 (7.28%) 
Investigations     
Weight decreased  1  67/411 (16.30%)  19/206 (9.22%) 
Metabolism and nutrition disorders     
Decreased appetite  1  74/411 (18.00%)  23/206 (11.17%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  13/411 (3.16%)  17/206 (8.25%) 
Muscle spasms  1  26/411 (6.33%)  9/206 (4.37%) 
Neck pain  1  11/411 (2.68%)  11/206 (5.34%) 
Nervous system disorders     
Dizziness  1  11/411 (2.68%)  13/206 (6.31%) 
Dysgeusia  1  34/411 (8.27%)  10/206 (4.85%) 
Headache  1  18/411 (4.38%)  12/206 (5.83%) 
Psychiatric disorders     
Anxiety  1  10/411 (2.43%)  12/206 (5.83%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  35/411 (8.52%)  30/206 (14.56%) 
Dysphonia  1  22/411 (5.35%)  17/206 (8.25%) 
Epistaxis  1  54/411 (13.14%)  3/206 (1.46%) 
Oropharyngeal pain  1  27/411 (6.57%)  14/206 (6.80%) 
Skin and subcutaneous tissue disorders     
Acne  1  22/411 (5.35%)  2/206 (0.97%) 
Dermatitis acneiform  1  112/411 (27.25%)  6/206 (2.91%) 
Dry skin  1  76/411 (18.49%)  16/206 (7.77%) 
Erythema  1  28/411 (6.81%)  5/206 (2.43%) 
Palmar-plantar erythrodysaesthesia syndrome  1  30/411 (7.30%)  0/206 (0.00%) 
Pruritus  1  58/411 (14.11%)  13/206 (6.31%) 
Rash  1  188/411 (45.74%)  34/206 (16.50%) 
Skin fissures  1  40/411 (9.73%)  1/206 (0.49%) 
Vascular disorders     
Hypertension  1  18/411 (4.38%)  12/206 (5.83%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.0
The trial was stopped prematurely due to futility.
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.
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Boehringer Ingelheim, Call Center
Organization: Boehringer Ingelheim
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT01345669    
Other Study ID Numbers: 1200.131
2011-000392-14 ( EudraCT Number: EudraCT )
First Submitted: April 28, 2011
First Posted: May 2, 2011
Results First Submitted: August 17, 2017
Results First Posted: October 23, 2017
Last Update Posted: December 7, 2017