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Trial record 1 of 1 for:    NCT00949650
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BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation

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ClinicalTrials.gov Identifier: NCT00949650
Recruitment Status : Completed
First Posted : July 30, 2009
Results First Posted : November 19, 2013
Last Update Posted : April 6, 2018
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Carcinoma, Non-Small-Cell Lung
Adenocarcinoma
Interventions Drug: Pemetrexed
Drug: BIBW 2992
Drug: Cisplatin
Enrollment 345
Recruitment Details  
Pre-assignment Details Two-arm, randomised (2:1 ratio), open-label, active-controlled, parallel-group comparison. 345 patients were randomised, 5 patients were not treated: 4 patients were not eligible for treatment and 1 patient in the chemotherapy arm refused to take study medication.
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Hide Arm/Group Description Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily. Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles.
Period Title: Overall Study
Started 230 [1] 115 [1]
Completed 0 [2] 0
Not Completed 230 115
Reason Not Completed
Progressive disease             188             19
Completed 6 courses of chemotherapy             0             60
Other Adverse Event (AE)             28             17
Protocol Violation             1             4
Refusal to continue medication             7             11
Not treated             1             4
Other not specified above             5             0
[1]
Treated patients.
[2]
On treatment at the cut-off date 17MAR2017.
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy Total
Hide Arm/Group Description Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily. Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles. Total of all reporting groups
Overall Number of Baseline Participants 230 115 345
Hide Baseline Analysis Population Description
Randomised Set (RS): The randomised set includes all patients who were randomised to receive treatment, whether treated or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 230 participants 115 participants 345 participants
60.5  (10.1) 59.9  (10.0) 60.3  (10.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants 115 participants 345 participants
Female
147
  63.9%
77
  67.0%
224
  64.9%
Male
83
  36.1%
38
  33.0%
121
  35.1%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 230 participants 115 participants 345 participants
Asian 166 83 249
Non-Asian 64 32 96
[1]
Measure Description: Race (Asian/non-Asian) was a stratification factor.
Epidermal Growth Factor Receptor (EGFR) mutation group   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 230 participants 115 participants 345 participants
EGFR mutation category: L858R 91 47 138
EGFR mutation category: Deletion Exon 19 112 57 169
EGFR mutation category: Other 27 11 38
[1]
Measure Description: EGFR mutation group (L858R/Deletion Exon 19/Other) was a stratification factor.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 230 participants 115 participants 345 participants
ECOG PS 0 (baseline) 92 41 133
ECOG PS 1 (baseline) 138 73 211
ECOG PS 2 (baseline) 0 1 1
[1]
Measure Description:

ECOG PS measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction.

  1. Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work.
  2. Ambulatory (>50 percent of waking hours), capable of all self-care, unable to carry out any work activities.
  3. Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours.
  4. Completely disabled, cannot carry on any self-care, totally confined to bed or chair.
  5. Dead.
1.Primary Outcome
Title Progression-Free Survival (PFS) Time
Hide Description PFS was defined as time from randomisation to disease progression or death whichever occured first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.
Time Frame Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set (RS)
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Hide Arm/Group Description:
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles.
Overall Number of Participants Analyzed 230 115
Median (95% Confidence Interval)
Unit of Measure: Months.
11.17
(9.63 to 13.70)
6.90
(5.39 to 8.25)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments Two-sided p-value from log-rank test stratified by EGFR mutation group and race.
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Regression, Cox
Comments Cox Proportional Hazard (PH) regression stratified by epidermal growth factor receptor (EGFR) mutation group and race.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.576
Confidence Interval 95%
0.426 to 0.778
Estimation Comments Afatinib 40 mg versus Pemetrexed/Cisplatin Chemotherapy.
2.Secondary Outcome
Title Percentage of Patients With Objective Response (OR)
Hide Description OR was defined as Complete Response (CR) or Partial Response (PR). Assessed by central independent review according to RECIST 1.1.
Time Frame Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Hide Outcome Measure Data
Hide Analysis Population Description
RS.
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Hide Arm/Group Description:
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles.
Overall Number of Participants Analyzed 230 115
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of patients with OR.
56.5
(49.8 to 63.0)
22.6
(15.3 to 31.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression stratified for EGFR mutation group and race.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.802
Confidence Interval 95%
2.855 to 8.075
Estimation Comments Afatinib 40 mg-Pemetrexed/Cisplatin Chemotherapy.
3.Secondary Outcome
Title Percentage of Participants With Disease Control (DC)
Hide Description DC was defined as a patient with OR or Stable Disease (SD). Assessed by central independent review according to the RECIST 1.1.
Time Frame Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Hide Outcome Measure Data
Hide Analysis Population Description
RS.
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Hide Arm/Group Description:
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles.
Overall Number of Participants Analyzed 230 115
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants with DC.
90.4
(85.9 to 93.9)
80.9
(72.5 to 87.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0118
Comments [Not Specified]
Method Regression, Logistic
Comments Logistic regression stratified for EGFR mutation group and race.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 2.288
Confidence Interval 95%
1.202 to 4.356
Estimation Comments Afatinib 40 mg-Pemetrexed/Cisplatin Chemotherapy.
4.Secondary Outcome
Title Overall Survival (OS) Time
Hide Description OS was defined as time from randomisation to death.
Time Frame From randomisation to cut-off date (17MAR2017).
Hide Outcome Measure Data
Hide Analysis Population Description
RS.
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Hide Arm/Group Description:
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles.
Overall Number of Participants Analyzed 230 115
Median (95% Confidence Interval)
Unit of Measure: Months.
28.16
(24.64 to 33.58)
28.22
(20.73 to 33.22)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7916
Comments Two-sided p-value from log-rank test stratified by EGFR mutation group and race.
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3850
Comments [Not Specified]
Method Regression, Cox
Comments Cox PH regression stratified by EGFR mutation group and race.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.880
Confidence Interval 95%
0.660 to 1.174
Estimation Comments Afatinib 40 mg-Pemetrexed/Cisplatin Chemotherapy.
5.Secondary Outcome
Title Tumour Shrinkage
Hide Description Tumour shrinkage was calculated as the minimum Sum of Diameters (SoD) of target lesions from all post-baseline tumour assessments, as read by the central independent review. The mean of these minimum values were presented after adjusting for baseline SoD, EGFR mutation group and race.
Time Frame Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Hide Outcome Measure Data
Hide Analysis Population Description
RS. There were only 203 patients in the Afatinib 40 mg arm and 101 patients in the Pemetrexed/Cisplatin Chemotherapy with tumour measurements.
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Hide Arm/Group Description:
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles.
Overall Number of Participants Analyzed 203 101
Mean (Standard Error)
Unit of Measure: mm.
33.19  (1.12) 43.00  (1.59)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Adjusted for baseline SoD, EGFR mutation group and race.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -9.82
Confidence Interval 95%
-13.64 to -5.99
Estimation Comments Afatinib 40 mg-Pemetrexed/Cisplatin Chemotherapy.
6.Secondary Outcome
Title Change From Baseline in Body Weight
Hide Description Because the PFS was longer for patients in the Afatinib arm than for patients in the chemotherapy arm, the period of data collection for ECOG status and body weight continued for a longer time in the Afatinib arm.
Time Frame Baseline and throughout the trial until progression (every 3 weeks), up to 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
RS. Only patients with baseline and at least one post-baseline assessment were included.
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Hide Arm/Group Description:
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles.
Overall Number of Participants Analyzed 224 109
Mean (Standard Deviation)
Unit of Measure: Kg.
Change from baseline at lowest value -3.95  (3.91) -2.68  (2.90)
Change from baseline at last value -1.19  (5.36) -0.29  (4.02)
7.Secondary Outcome
Title Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Hide Description

ECOG PS measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction.

  1. Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work.
  2. Ambulatory (>50 percent of waking hours), capable of all self-care, unable to carry out any work activities.
  3. Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours.
  4. Completely disabled, cannot carry on any self-care, totally confined to bed or chair.
  5. Dead.
Time Frame Throughout the trial until progression (every 3 weeks), up to 28 months.
Hide Outcome Measure Data
Hide Analysis Population Description
RS. Only patients with baseline and at least one post-baseline assessment were included.
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Hide Arm/Group Description:
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles.
Overall Number of Participants Analyzed 228 111
Measure Type: Number
Unit of Measure: Participants
ECOG PS 0 (last value) 92 41
ECOG PS 1 (last value) 138 73
ECOG PS 2 (last value) 0 1
8.Secondary Outcome
Title Health Related Quality of Life (HRQOL): Time to Deterioration in Coughing
Hide Description HRQOL was measured by European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire C30 (QLQ-C30) and its lung cancer specific module LC13 (QLQ-LC13). Analysis for cough is based on QLQ-LC13 question 1. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.
Time Frame Throughout the trial until progression (every 3 weeks).
Hide Outcome Measure Data
Hide Analysis Population Description
RS.
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Hide Arm/Group Description:
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles.
Overall Number of Participants Analyzed 230 115
Median (95% Confidence Interval)
Unit of Measure: Months.
26.97 [1] 
(19.22 to NA)
8.02 [2] 
(4.44 to NA)
[1]
As only 82 patients (35.7 percent) in the Afatinib 40 mg deteriorated, the upper limit of Confidence Interval (CI) was not estimable.
[2]
As only 44 patients (38.3 percent) in the Pemetrexed/Cisplatin Chemotherapy deteriorated, the upper limit of the CI was not estimable.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0062
Comments Two-sided p-value from log-rank test stratified by EGFR mutation group and race.
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2133
Comments [Not Specified]
Method Regression, Cox
Comments Cox PH regression stratified by EGFR mutation group and race.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.589
Confidence Interval 95%
0.401 to 0.866
Estimation Comments Afatinib 40 mg vs. Pemetrexed/Cisplatin Chemotherapy, if HR<1 then favours Afatinib 40 mg.
9.Secondary Outcome
Title HRQOL: Time to Deterioration in Dyspnoea
Hide Description HRQOL was measured by EORTC QLQ-C30 and its lung cancer specific module QLQ-LC13. Analysis for dyspnoea is based on composite of QLQ-LC13 questions 3-5. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.
Time Frame Throughout the trial until progression (every 3 weeks).
Hide Outcome Measure Data
Hide Analysis Population Description
RS.
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Hide Arm/Group Description:
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles.
Overall Number of Participants Analyzed 230 115
Median (95% Confidence Interval)
Unit of Measure: Months.
10.41
(5.59 to 15.93)
2.86
(2.17 to 4.90)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0129
Comments Two-sided p-value from log-rank test stratified by EGFR mutation group and race.
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0078
Comments [Not Specified]
Method Regression, Cox
Comments Cox PH regression stratified by EGFR mutation group and race.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.680
Confidence Interval 95%
0.499 to 0.927
Estimation Comments Afatinib 40 mg vs. Pemetrexed/Cisplatin Chemotherapy, if HR<1 then favours Afatinib 40 mg.
10.Secondary Outcome
Title HRQOL: Time to Deterioration in Pain
Hide Description HRQOL was measured by EORTC QLQ-C30 and its lung cancer specific module QLQ-LC13. Analysis for pain is based on composite of QLQ-C30 questions 9 and 19. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.
Time Frame Throughout the trial until progression (every 3 weeks).
Hide Outcome Measure Data
Hide Analysis Population Description
RS.
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Hide Arm/Group Description:
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles.
Overall Number of Participants Analyzed 230 115
Median (95% Confidence Interval)
Unit of Measure: Months.
4.17
(2.79 to 5.59)
3.09
(2.17 to 3.98)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1882
Comments Two-sided p-value from log-rank test stratified by EGFR mutation group and race.
Method Log Rank
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Afatinib 40 mg, Pemetrexed/Cisplatin Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0427
Comments [Not Specified]
Method Regression, Cox
Comments Cox PH regression stratified by EGFR mutation group and race.
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.826
Confidence Interval 95%
0.618 to 1.104
Estimation Comments Afatinib 40 mg vs. Pemetrexed/Cisplatin Chemotherapy, if HR<1 then favours Afatinib 40 mg.
11.Secondary Outcome
Title Trough Plasma Concentrations of Afatinib at Day 22
Hide Description Trough plasma concentrations of Afatinib at Day 22 (course 2, visit 1) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.
Time Frame Day 22.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the treated set with evaluable data and who had at least 1 valid Afatinib plasma concentration available on this time point.
Arm/Group Title Afatinib 20 mg Afatinib 30 mg Afatinib 40 mg Afatinib 50 mg
Hide Arm/Group Description:
Patients received Afatinib monotherapy 20 mg film-coated tablets orally once daily after a dose reduction.
Patients received Afatinib monotherapy 30 mg film-coated tablets orally once daily after a dose reduction.
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Afatinib monotherapy 50 mg film-coated tablets orally once daily after a dose escalation.
Overall Number of Participants Analyzed 0 11 165 3
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL.
21.8
(36.6%)
28.0
(85.0%)
29.9
(46.1%)
12.Secondary Outcome
Title Trough Plasma Concentrations of Afatinib at Day 29
Hide Description Trough plasma concentrations of Afatinib at day 29 (course 2, visit 2) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.
Time Frame Day 29.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the treated set with evaluable data and who had at least 1 valid Afatinib plasma concentration available on this time point.
Arm/Group Title Afatinib 20 mg Afatinib 30 mg Afatinib 40 mg Afatinib 50 mg
Hide Arm/Group Description:
Patients received Afatinib monotherapy 20 mg film-coated tablets orally once daily after a dose reduction.
Patients received Afatinib monotherapy 30 mg film-coated tablets orally once daily after a dose reduction.
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Afatinib monotherapy 50 mg film-coated tablets orally once daily after a dose escalation.
Overall Number of Participants Analyzed 0 25 143 16
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL.
28.0
(82.4%)
25.8
(69.5%)
29.6
(79.2%)
13.Secondary Outcome
Title Trough Plasma Concentrations of Afatinib at Day 43
Hide Description Trough plasma concentrations of Afatinib at Day 43 (course 3, visit 1) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.
Time Frame Day 43.
Hide Outcome Measure Data
Hide Analysis Population Description
Patients from the treated set with evaluable data and who had at least 1 valid Afatinib plasma concentration available on this time point.
Arm/Group Title Afatinib 20 mg Afatinib 30 mg Afatinib 40 mg Afatinib 50 mg
Hide Arm/Group Description:
Patients received Afatinib monotherapy 20 mg film-coated tablets orally once daily after a dose reduction.
Patients received Afatinib monotherapy 30 mg film-coated tablets orally once daily after a dose reduction.
Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily.
Patients received Afatinib monotherapy 50 mg film-coated tablets orally once daily after a dose escalation.
Overall Number of Participants Analyzed 2 39 126 14
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL.
24.4
(260%)
24.7
(63.9%)
23.5
(66.2%)
27.5
(64.4%)
Time Frame First administration of trial medication until 28 days after last administration of trial medication.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Hide Arm/Group Description Patients received Afatinib monotherapy 40 mg film-coated tablets orally once daily. Patients received Pemetrexed 500 mg/m^2 lyophilised powder as intravenous infusion after Cisplatin 75 mg/m^2 solution for infusion as intravenous infusion on Day 1 of each 21-day treatment course up to 6 cycles.
All-Cause Mortality
Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Hide Serious Adverse Events
Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   72/229 (31.44%)   25/111 (22.52%) 
Blood and lymphatic system disorders     
Anaemia  1  0/229 (0.00%)  2/111 (1.80%) 
Thrombocytopenia  1  0/229 (0.00%)  1/111 (0.90%) 
Cardiac disorders     
Atrial fibrillation  1  0/229 (0.00%)  1/111 (0.90%) 
Mitral valve incompetence  1  1/229 (0.44%)  0/111 (0.00%) 
Myocardial infarction  1  0/229 (0.00%)  1/111 (0.90%) 
Pericardial effusion  1  1/229 (0.44%)  0/111 (0.00%) 
Eye disorders     
Cataract  1  1/229 (0.44%)  0/111 (0.00%) 
Gastrointestinal disorders     
Abdominal discomfort  1  1/229 (0.44%)  0/111 (0.00%) 
Abdominal pain upper  1  1/229 (0.44%)  0/111 (0.00%) 
Diarrhoea  1  15/229 (6.55%)  0/111 (0.00%) 
Gastritis  1  1/229 (0.44%)  0/111 (0.00%) 
Gastrooesophageal reflux disease  1  1/229 (0.44%)  0/111 (0.00%) 
Haemorrhoids  1  1/229 (0.44%)  0/111 (0.00%) 
Nausea  1  0/229 (0.00%)  2/111 (1.80%) 
Pancreatitis acute  1  1/229 (0.44%)  0/111 (0.00%) 
Stomatitis  1  1/229 (0.44%)  1/111 (0.90%) 
Vomiting  1  11/229 (4.80%)  3/111 (2.70%) 
General disorders     
Abasia  1  0/229 (0.00%)  1/111 (0.90%) 
Asthenia  1  1/229 (0.44%)  2/111 (1.80%) 
Death  1  2/229 (0.87%)  1/111 (0.90%) 
Disease progression  1  2/229 (0.87%)  0/111 (0.00%) 
Fatigue  1  3/229 (1.31%)  1/111 (0.90%) 
General physical health deterioration  1  1/229 (0.44%)  1/111 (0.90%) 
Hernia  1  1/229 (0.44%)  0/111 (0.00%) 
Malaise  1  0/229 (0.00%)  1/111 (0.90%) 
Mucosal inflammation  1  2/229 (0.87%)  0/111 (0.00%) 
Pyrexia  1  2/229 (0.87%)  1/111 (0.90%) 
Hepatobiliary disorders     
Cholecystitis acute  1  2/229 (0.87%)  0/111 (0.00%) 
Jaundice  1  1/229 (0.44%)  0/111 (0.00%) 
Infections and infestations     
Cellulitis  1  1/229 (0.44%)  1/111 (0.90%) 
Device related infection  1  1/229 (0.44%)  0/111 (0.00%) 
Lower respiratory tract infection  1  2/229 (0.87%)  0/111 (0.00%) 
Lung infection  1  1/229 (0.44%)  0/111 (0.00%) 
Meningitis aseptic  1  1/229 (0.44%)  0/111 (0.00%) 
Meningoencephalitis herpetic  1  0/229 (0.00%)  1/111 (0.90%) 
Pneumonia  1  4/229 (1.75%)  1/111 (0.90%) 
Sepsis  1  1/229 (0.44%)  0/111 (0.00%) 
Upper respiratory tract infection  1  2/229 (0.87%)  0/111 (0.00%) 
Urinary tract infection  1  2/229 (0.87%)  0/111 (0.00%) 
Injury, poisoning and procedural complications     
Femur fracture  1  1/229 (0.44%)  0/111 (0.00%) 
Lower limb fracture  1  1/229 (0.44%)  0/111 (0.00%) 
Splenic rupture  1  1/229 (0.44%)  0/111 (0.00%) 
Synovial rupture  1  0/229 (0.00%)  1/111 (0.90%) 
Thoracic vertebral fracture  1  1/229 (0.44%)  0/111 (0.00%) 
Tibia fracture  1  1/229 (0.44%)  0/111 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  0/229 (0.00%)  1/111 (0.90%) 
Aspartate aminotransferase increased  1  0/229 (0.00%)  1/111 (0.90%) 
Blood sodium decreased  1  0/229 (0.00%)  1/111 (0.90%) 
Liver function test abnormal  1  1/229 (0.44%)  0/111 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  2/229 (0.87%)  0/111 (0.00%) 
Dehydration  1  3/229 (1.31%)  1/111 (0.90%) 
Diabetes with hyperosmolarity  1  0/229 (0.00%)  1/111 (0.90%) 
Hypokalaemia  1  4/229 (1.75%)  1/111 (0.90%) 
Hyponatraemia  1  1/229 (0.44%)  0/111 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  0/229 (0.00%)  1/111 (0.90%) 
Bone pain  1  1/229 (0.44%)  0/111 (0.00%) 
Muscular weakness  1  0/229 (0.00%)  1/111 (0.90%) 
Pain in extremity  1  1/229 (0.44%)  0/111 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Malignant neoplasm progression  1  3/229 (1.31%)  2/111 (1.80%) 
Metastases to central nervous system  1  3/229 (1.31%)  0/111 (0.00%) 
Metastases to lung  1  0/229 (0.00%)  1/111 (0.90%) 
Metastases to meninges  1  1/229 (0.44%)  0/111 (0.00%) 
Neoplasm progression  1  2/229 (0.87%)  0/111 (0.00%) 
Nervous system disorders     
Depressed level of consciousness  1  1/229 (0.44%)  0/111 (0.00%) 
Epilepsy  1  1/229 (0.44%)  0/111 (0.00%) 
Headache  1  1/229 (0.44%)  0/111 (0.00%) 
Intracranial pressure increased  1  1/229 (0.44%)  0/111 (0.00%) 
Loss of consciousness  1  1/229 (0.44%)  0/111 (0.00%) 
Partial seizures  1  1/229 (0.44%)  0/111 (0.00%) 
Seizure  1  3/229 (1.31%)  0/111 (0.00%) 
Syncope  1  0/229 (0.00%)  1/111 (0.90%) 
Psychiatric disorders     
Confusional state  1  3/229 (1.31%)  0/111 (0.00%) 
Schizophreniform disorder  1  0/229 (0.00%)  1/111 (0.90%) 
Renal and urinary disorders     
Acute kidney injury  1  0/229 (0.00%)  1/111 (0.90%) 
Acute prerenal failure  1  1/229 (0.44%)  1/111 (0.90%) 
Renal failure  1  1/229 (0.44%)  0/111 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  2/229 (0.87%)  0/111 (0.00%) 
Bronchospasm  1  0/229 (0.00%)  1/111 (0.90%) 
Dyspnoea  1  4/229 (1.75%)  2/111 (1.80%) 
Epistaxis  1  0/229 (0.00%)  1/111 (0.90%) 
Haemoptysis  1  1/229 (0.44%)  1/111 (0.90%) 
Interstitial lung disease  1  1/229 (0.44%)  0/111 (0.00%) 
Pleural effusion  1  2/229 (0.87%)  3/111 (2.70%) 
Pneumothorax  1  1/229 (0.44%)  1/111 (0.90%) 
Pulmonary artery thrombosis  1  0/229 (0.00%)  1/111 (0.90%) 
Pulmonary embolism  1  2/229 (0.87%)  1/111 (0.90%) 
Respiratory arrest  1  1/229 (0.44%)  0/111 (0.00%) 
Respiratory failure  1  1/229 (0.44%)  0/111 (0.00%) 
Skin and subcutaneous tissue disorders     
Dermatitis  1  1/229 (0.44%)  0/111 (0.00%) 
Vascular disorders     
Deep vein thrombosis  1  2/229 (0.87%)  0/111 (0.00%) 
Hypotension  1  1/229 (0.44%)  0/111 (0.00%) 
Superior vena cava syndrome  1  1/229 (0.44%)  0/111 (0.00%) 
Thrombosis  1  0/229 (0.00%)  1/111 (0.90%) 
Venous thrombosis  1  1/229 (0.44%)  1/111 (0.90%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Afatinib 40 mg Pemetrexed/Cisplatin Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   229/229 (100.00%)   108/111 (97.30%) 
Blood and lymphatic system disorders     
Anaemia  1  19/229 (8.30%)  29/111 (26.13%) 
Leukopenia  1  6/229 (2.62%)  21/111 (18.92%) 
Neutropenia  1  4/229 (1.75%)  35/111 (31.53%) 
Thrombocytopenia  1  1/229 (0.44%)  8/111 (7.21%) 
Eye disorders     
Dry eye  1  14/229 (6.11%)  0/111 (0.00%) 
Vision blurred  1  12/229 (5.24%)  2/111 (1.80%) 
Gastrointestinal disorders     
Abdominal pain  1  13/229 (5.68%)  5/111 (4.50%) 
Abdominal pain upper  1  15/229 (6.55%)  8/111 (7.21%) 
Cheilitis  1  22/229 (9.61%)  0/111 (0.00%) 
Constipation  1  37/229 (16.16%)  39/111 (35.14%) 
Diarrhoea  1  216/229 (94.32%)  25/111 (22.52%) 
Dyspepsia  1  21/229 (9.17%)  7/111 (6.31%) 
Mouth ulceration  1  24/229 (10.48%)  3/111 (2.70%) 
Nausea  1  65/229 (28.38%)  75/111 (67.57%) 
Stomatitis  1  88/229 (38.43%)  10/111 (9.01%) 
Vomiting  1  53/229 (23.14%)  50/111 (45.05%) 
General disorders     
Asthenia  1  16/229 (6.99%)  14/111 (12.61%) 
Chest pain  1  16/229 (6.99%)  14/111 (12.61%) 
Fatigue  1  45/229 (19.65%)  39/111 (35.14%) 
Malaise  1  7/229 (3.06%)  6/111 (5.41%) 
Mucosal inflammation  1  67/229 (29.26%)  5/111 (4.50%) 
Oedema  1  7/229 (3.06%)  13/111 (11.71%) 
Oedema peripheral  1  17/229 (7.42%)  8/111 (7.21%) 
Pyrexia  1  28/229 (12.23%)  6/111 (5.41%) 
Infections and infestations     
Conjunctivitis  1  28/229 (12.23%)  3/111 (2.70%) 
Cystitis  1  15/229 (6.55%)  1/111 (0.90%) 
Folliculitis  1  12/229 (5.24%)  0/111 (0.00%) 
Nasopharyngitis  1  39/229 (17.03%)  9/111 (8.11%) 
Paronychia  1  132/229 (57.64%)  0/111 (0.00%) 
Upper respiratory tract infection  1  29/229 (12.66%)  4/111 (3.60%) 
Urinary tract infection  1  19/229 (8.30%)  5/111 (4.50%) 
Investigations     
Alanine aminotransferase increased  1  27/229 (11.79%)  3/111 (2.70%) 
Aspartate aminotransferase increased  1  22/229 (9.61%)  1/111 (0.90%) 
Blood creatinine increased  1  5/229 (2.18%)  10/111 (9.01%) 
Haemoglobin decreased  1  3/229 (1.31%)  13/111 (11.71%) 
Neutrophil count decreased  1  1/229 (0.44%)  8/111 (7.21%) 
Weight decreased  1  44/229 (19.21%)  16/111 (14.41%) 
Metabolism and nutrition disorders     
Decreased appetite  1  70/229 (30.57%)  61/111 (54.95%) 
Hypokalaemia  1  21/229 (9.17%)  4/111 (3.60%) 
Hyponatraemia  1  4/229 (1.75%)  6/111 (5.41%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  21/229 (9.17%)  6/111 (5.41%) 
Back pain  1  37/229 (16.16%)  13/111 (11.71%) 
Muscle spasms  1  20/229 (8.73%)  0/111 (0.00%) 
Musculoskeletal pain  1  21/229 (9.17%)  2/111 (1.80%) 
Myalgia  1  12/229 (5.24%)  1/111 (0.90%) 
Pain in extremity  1  20/229 (8.73%)  4/111 (3.60%) 
Nervous system disorders     
Dizziness  1  28/229 (12.23%)  12/111 (10.81%) 
Dysgeusia  1  18/229 (7.86%)  9/111 (8.11%) 
Headache  1  37/229 (16.16%)  19/111 (17.12%) 
Psychiatric disorders     
Insomnia  1  37/229 (16.16%)  10/111 (9.01%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  39/229 (17.03%)  21/111 (18.92%) 
Dyspnoea  1  18/229 (7.86%)  12/111 (10.81%) 
Epistaxis  1  41/229 (17.90%)  1/111 (0.90%) 
Hiccups  1  5/229 (2.18%)  10/111 (9.01%) 
Nasal inflammation  1  15/229 (6.55%)  0/111 (0.00%) 
Oropharyngeal pain  1  13/229 (5.68%)  3/111 (2.70%) 
Rhinorrhoea  1  16/229 (6.99%)  7/111 (6.31%) 
Skin and subcutaneous tissue disorders     
Acne  1  52/229 (22.71%)  0/111 (0.00%) 
Alopecia  1  30/229 (13.10%)  20/111 (18.02%) 
Dermatitis acneiform  1  32/229 (13.97%)  0/111 (0.00%) 
Dry skin  1  72/229 (31.44%)  2/111 (1.80%) 
Nail disorder  1  14/229 (6.11%)  0/111 (0.00%) 
Palmar-plantar erythrodysaesthesia syndrome  1  19/229 (8.30%)  0/111 (0.00%) 
Pruritus  1  50/229 (21.83%)  1/111 (0.90%) 
Rash  1  145/229 (63.32%)  11/111 (9.91%) 
Skin exfoliation  1  13/229 (5.68%)  0/111 (0.00%) 
Skin fissures  1  16/229 (6.99%)  0/111 (0.00%) 
Vascular disorders     
Hypertension  1  14/229 (6.11%)  14/111 (12.61%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 19.1
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
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00949650    
Other Study ID Numbers: 1200.32
2008-005615-18 ( EudraCT Number )
First Submitted: July 29, 2009
First Posted: July 30, 2009
Results First Submitted: August 8, 2013
Results First Posted: November 19, 2013
Last Update Posted: April 6, 2018