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LUME-Lung 1: BIBF 1120 Plus Docetaxel as Compared to Placebo Plus Docetaxel in 2nd Line Non Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00805194
Recruitment Status : Completed
First Posted : December 9, 2008
Results First Posted : December 1, 2014
Last Update Posted : December 5, 2018
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 Carcinoma, Non-Small-Cell Lung
Interventions Drug: placebo plus docetaxel
Drug: BIBF 1120 plus docetaxel
Enrollment 1314
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h). Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Period Title: Overall Study
Started 655 [1] 659 [1]
Completed 6 5
Not Completed 649 654
Reason Not Completed
Progressive disease (modified RECIST)             404             435
Worsening or AE of underlying disease             64             70
Other AE             84             73
Protocol Violation             9             9
Lost to Follow-up             5             5
Withdrawal by Subject             60             42
Not treated             3             4
Reasons other than stated above             20             16
[1]
randomised patients
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel Total
Hide Arm/Group Description Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h). Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h). Total of all reporting groups
Overall Number of Baseline Participants 655 659 1314
Hide Baseline Analysis Population Description
Randomised Set (RS)- Includes all randomised patients, whether patients had received study treatment or not
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 655 participants 659 participants 1314 participants
59.7  (9.7) 59.8  (9.0) 59.7  (9.3)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 655 participants 659 participants 1314 participants
Female
179
  27.3%
180
  27.3%
359
  27.3%
Male
476
  72.7%
479
  72.7%
955
  72.7%
Tumour histology  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 655 participants 659 participants 1314 participants
Adenocarcinoma
322
  49.2%
336
  51.0%
658
  50.1%
Squamous cell carcinoma
276
  42.1%
279
  42.3%
555
  42.2%
Other
57
   8.7%
44
   6.7%
101
   7.7%
Number of patients with adenocarcinoma and time since first line therapy in categories   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 322 participants 336 participants 658 participants
<9 month
206
  64.0%
199
  59.2%
405
  61.6%
>=9 month
112
  34.8%
134
  39.9%
246
  37.4%
Missing
4
   1.2%
3
   0.9%
7
   1.1%
[1]
Measure Analysis Population Description: Randomised patients with adenocarcinoma and time since first line therapy.
1.Primary Outcome
Title Progression Free Survival (PFS) as Assessed by Central Independent Review
Hide Description

Progression Free Survival (PFS) as assessed by central independent review according to the modified Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) . Progression free survival (PFS) is defined as the duration of time from date of randomisation to date of progression or death (whatever occurs earlier).

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Time Frame From randomisation until cut-off date 2 November 2010 (when 713 PFS events were observed)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 565 569
Median (Inter-Quartile Range)
Unit of Measure: months
3.4
(1.5 to 5.7)
2.7
(1.4 to 4.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nintedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments HR, Confidence Interval (CI) and p-value obtained from the proportional hazards model stratified by baseline ECOG PS (0 vs 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0019
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.68 to 0.92
Estimation Comments Hazard Ratio (HR) below 1 favors nintedanib
2.Secondary Outcome
Title Overall Survival (Key Secondary Endpoint)
Hide Description

Overall Survival (OS) defined as the duration from randomisation to death (irrespective of the reason of death). Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

A fixed-sequence-testing was implemented for key secondary endpoint if both the primary and the follow-up analysis showed a treatment benefit (P<0.05) of nintedanib over placebo. In this case, the OS would be tested using hierarchical testing of statistical hypotheses in (1) patients with adenocarcinoma and <9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been.

Time Frame From randomisation until cut-off date 15 February 2013 (approximately 48 months or 1151 deaths among all patients )
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 655 659
Median (Inter-Quartile Range)
Unit of Measure: months
Adenocarcinoma and <9 months Number Analyzed 206 participants 199 participants
10.9
(5.1 to 21.9)
7.9
(4.5 to 14.5)
Adenocarcinoma Number Analyzed 322 participants 336 participants
12.6
(5.5 to 24.2)
10.3
(5.5 to 19.9)
All patients Number Analyzed 655 participants 659 participants
10.1
(5.0 to 19.4)
9.1
(4.8 to 17.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nintedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments

Hierarchical testing was tested in a fixed sequence of statistical hypotheses in (1) patients with adenocarcinoma and <9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been rejected.

Overall survival for patients with adenocarcinoma and <9 months since start of first line therapy.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0073
Comments HR, CI and p-value obtained from the prop. hazards model stratified by baseline ECOG PS (0 vs 1 - one pat. had 2), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.60 to 0.92
Estimation Comments

The overall alpha level followed a Lan-DeMets spending function with O’Brien-Fleming shape parameter to preserve an overall 2-sided alpha level of 0.05.

HR below 1 favors nintedanib

Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nintedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments

Hierarchical testing was tested in a fixed sequence of statistical hypotheses in (1) patients with adenocarcinoma and <9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been rejected.

Overall survival for patients with adenocarcinoma.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0359
Comments HR, CI and p-value obtained from the prop. hazards model stratified by baseline ECOG PS (0 vs 1 - one pat. had 2), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.70 to 0.99
Estimation Comments

The overall alpha level followed a Lan-DeMets spending function with O’Brien-Fleming shape parameter to preserve an overall 2-sided alpha level of 0.05.

HR below 1 favors nintedanib

Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Nintedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments

Hierarchical testing was tested in a fixed sequence of statistical hypotheses in (1) patients with adenocarcinoma and <9 months since start of first-line therapy, (2) patients with adenocarcinoma, and (3) all patients. Each hypothesis could be only tested at the pre-specified alpha level if the previous null hypothesis in the testing sequence had been rejected.

Overall survival for all patients.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2720
Comments HR, CI and p-value obtained from the prop. hazards model stratified by baseline ECOG PS (0 vs 1 - one pat. had 2), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.94
Confidence Interval (2-Sided) 95%
0.83 to 1.05
Estimation Comments The overall alpha level followed a Lan-DeMets spending function with O’Brien-Fleming shape parameter to preserve an overall 2-sided alpha level of 0.05. HR below 1 favors nintedanib
3.Secondary Outcome
Title Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Central Independent Review
Hide Description

Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by central independent review according to the modified RECIST (version 1.0) criteria.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Time Frame From randomisation until cut-off date 15 February 2013
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 655 659
Median (Inter-Quartile Range)
Unit of Measure: months
3.5
(1.5 to 5.7)
2.7
(1.4 to 5.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nintedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0070
Comments HR, CI and p-value obtained from the proportional hazards model stratified by baseline ECOG PS (0 vs 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.75 to 0.96
Estimation Comments HR below 1 favors nintedanib
4.Secondary Outcome
Title Follow-up Analysis of Progression Free Survival (PFS) as Assessed by Investigator
Hide Description

Follow-up analysis was conducted at the time of overall survival analysis. Progression Free Survival (PFS) as assessed by investigator according to the modified RECIST (version 1.0) criteria.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Time Frame From randomisation until cut-off date 15 February 2013
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 655 659
Median (Inter-Quartile Range)
Unit of Measure: months
4.2
(2.1 to 7.1)
3.0
(1.4 to 5.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nintedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0012
Comments HR, CI and p-value obtained from the proportional hazards model stratified by baseline ECOG PS (0 vs 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.73 to 0.93
Estimation Comments HR below 1 favors nintedanib
5.Secondary Outcome
Title Objective Tumour Response
Hide Description

Confirmed objective response is defined as confirmed Complete Response (CR) and Partial Response (PR) and evaluated according to the modified RECIST criteria version 1.0.

As per RECIST v1.0, Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Time Frame From randomisation until cut-off date 15 February 2013
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 655 659
Measure Type: Number
Unit of Measure: % of participants
central independent reviewer 4.4 3.3
investigator assessment 10.4 7.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nintedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments Analysis based on the central independent review
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3067
Comments Odds ratio and p-value are obtained from logistic regression model adjusted for baseline ECOG PS (0 vs 1)
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.34
Confidence Interval (2-Sided) 95%
0.76 to 2.39
Estimation Comments An odds ratio >1 indicates a benefit to nintedanib
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nintedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments Analysis based on the investigator's assessment
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0761
Comments Odds ratio and p-value are obtained from logistic regression model adjusted for baseline ECOG PS (0 vs 1)
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.41
Confidence Interval (2-Sided) 95%
0.96 to 2.08
Estimation Comments An odds ratio >1 indicates a benefit to nintedanib
6.Secondary Outcome
Title Duration of Confirmed Objective Tumour Response
Hide Description

The duration of objective response is the time from first documented (CR) or (PR) to the time of progression or death and evaluated according to the modified RECIST criteria version 1.0.

As per RECIST v1.0, Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Time Frame From randomisation until cut-off date 15 February 2013
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 655 659
Median (Inter-Quartile Range)
Unit of Measure: months
central independent reviewer Number Analyzed 29 participants 22 participants
4.3
(3.0 to 5.7)
4.3
(2.8 to 8.5)
investigator assessment Number Analyzed 68 participants 50 participants
5.7
(4.1 to 10.0)
5.5
(3.9 to 9.6)
7.Secondary Outcome
Title Time to Confirmed Objective Tumour Response
Hide Description

Time to confirmed objective response is defined as time from randomisation to the date of first documented (CR) or (PR) and evaluated according to the modified RECIST criteria version 1.0.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Time Frame From randomisation until cut-off date 15 February 2013
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 655 659
Median (Inter-Quartile Range)
Unit of Measure: months
central independent reviewer Number Analyzed 29 participants 22 participants
1.5
(1.4 to 3.0)
2.9
(1.4 to 5.6)
investigator assessment Number Analyzed 68 participants 50 participants
2.6
(1.4 to 4.0)
2.7
(1.4 to 4.1)
8.Secondary Outcome
Title Disease Control
Hide Description

Disease control was defined as a best overall response of Complete Response (CR), Partial Response (PR), or Stable Disease (SD) and evaluated according to the modified RECIST criteria version 1.0.

As per RECIST v1.0 for target lesions : Complete Response (CR), disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Time Frame From randomisation until cut-off date 15 February 2013
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 (with dose reduction to 60 mg/m2 if required) once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 655 659
Measure Type: Number
Unit of Measure: % of participants
central independent reviewer Number Analyzed 354 participants 272 participants
54.0 41.3
investigator assessment Number Analyzed 415 participants 339 participants
63.4 51.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nintedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments Analysis based on the central independent review
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Odds ratio and p-value are obtained from logistic regression model adjusted for baseline ECOG PS (0 vs 1)
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.68
Confidence Interval (2-Sided) 95%
1.35 to 2.09
Estimation Comments An odds ratio >1 indicates a benefit to nintedanib
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nintedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments Analysis based on investigator's assessment
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments Odds ratio and p-value are obtained from logistic regression model adjusted for baseline ECOG PS (0 vs 1)
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.64
Confidence Interval (2-Sided) 95%
1.31 to 2.05
Estimation Comments An odds ratio >1 indicates a benefit to nintedanib
9.Secondary Outcome
Title Duration of Disease Control
Hide Description

The duration of disease control was defined as the time from randomisation to the date of disease progression or death (which ever occurs first) for patients with disease control.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Time Frame From randomisation until cut-off date 15 February 2013
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 655 659
Median (Inter-Quartile Range)
Unit of Measure: months
central independent reviewer Number Analyzed 354 participants 272 participants
5.6
(4.1 to 7.1)
5.6
(4.0 to 8.2)
investigator assessment Number Analyzed 415 participants 339 participants
5.7
(4.2 to 8.4)
5.6
(4.1 to 8.5)
10.Secondary Outcome
Title Change From Baseline in Tumour Size
Hide Description

Percentage change from baseline in tumour size is defined as decrease in the sum of the longest diameter of the target lesion.

Presented means are in fact adjusted best means percentage changes generated from ANOVA model adjusted for baseline ECOG PS (0 vs. 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)

This endpoint was analysed based on the central independent reviewer as well as the investigator.

Time Frame From randomisation until cut-off date 15 February 2013
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised Set
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 655 659
Mean (95% Confidence Interval)
Unit of Measure: percentage of change in tumor size in mm
central independent reviewer Number Analyzed 582 participants 570 participants
-4.87
(-6.62 to -3.12)
0.58
(-1.19 to 2.35)
investigator assessment Number Analyzed 603 participants 596 participants
-10.34
(-12.58 to -8.11)
-2.14
(-4.39 to 0.10)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nintedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments Analysis based on the central independent review
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value generated from ANOVA model adjusted for baseline ECOG PS (0 vs. 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)
Method ANOVA
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nintedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments Analysis based on the investigator's assessment
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value generated from ANOVA model adjusted for baseline ECOG PS (0 vs. 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)
Method ANOVA
Comments [Not Specified]
11.Secondary Outcome
Title Clinical Improvement
Hide Description

Clinical improvement was defined as the time from randomisation to deterioration in body weight and/or Eastern Cooperative Oncology group performance score (ECOG PS) whichever occurred first.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve.

Time Frame From randomisation until cut-off date 15 February 2013
Hide Outcome Measure Data
Hide Analysis Population Description
Randomised set
Arm/Group Title Nitedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 655 659
Median (Inter-Quartile Range)
Unit of Measure: months
5.9
(2.1 to 22.7)
5.2
(2.1 to 19.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nitedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7282
Comments HR, CI and p-value obtained from the prop. hazards model stratified by baseline ECOG PS (0 vs 1 - one pat.had 2), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.87 to 1.21
Estimation Comments HR below 1 favors nintedanib
12.Secondary Outcome
Title Quality of Life (QoL)
Hide Description

Quality of life (QoL) was measured by standardised questionnaires (Health Status Self-Assessment Questionnaire (EQ-5D), EORTC Quality of life questionnaire - Core 30 (EORTC QLQ-C30), Quality of life questionnaire - lung cancer module (EORTC QLQ-LC13). The EORTC QLQ-C30 comprises of 30 questions, using both multi-item scales and single-item measures. EORTC LC-13 comprises of 13 questions incorporating 1 multi-item scale and a series of single items.

The following were the main points of interest:

Time to deterioration of cough (EORTC QLQ-LC13 question 1), Time to deterioration of dyspnoea (QLQ-LC13, composite of questions 3 to 5), Time to deterioration of pain (QLQ- C30, composite of questions 9 and 19).

Time to deterioration of cough, dyspnoea and pain was defined as the time to a 10-point increase from the baseline score.

Median, 25th and 75th percentiles are calculated from an unadjusted Kaplan-Meier curve

Time Frame From randomisation until cut-off date 15 February 2013
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Hide Analysis Population Description
Randomised set
Arm/Group Title Nitedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 655 659
Median (Inter-Quartile Range)
Unit of Measure: months
Time to deterioration of cough
4.3
(1.6 to 11.8)
3.5
(1.5 to 12.6)
Time to deterioration of dyspnoea
2.0
(0.8 to 4.2)
2.1
(0.8 to 4.5)
Time to deterioration of pain
2.8
(1.1 to 6.5)
2.6
(0.8 to 5.8)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Nitedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments Analysis evaluating the time to deterioration of cough
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1858
Comments HR, CI and p-value obtained from the prop. hazards model stratified by baseline ECOG PS (0 vs >=1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.77 to 1.05
Estimation Comments HR below 1 favors nintedanib
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Nitedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments Analysis evaluating the time to deterioration of dyspnoea
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5203
Comments HR, CI and p-value obtained from the prop. hazards model stratified by baseline ECOG PS (0 vs >=1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.91 to 1.20
Estimation Comments HR below 1 favors nintedanib
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Nitedanib Plus Docetaxel, Placebo Plus Docetaxel
Comments Analysis evaluating the time to deterioration of pain
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4373
Comments HR, CI and p-value obtained from the prop. hazards model stratified by baseline ECOG PS (0 vs >= 1), tumour histology (squamous vs non-squamous), brain metastases at baseline (yes vs no) and prior treatment with bevacizumab (yes vs no)
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.82 to 1.09
Estimation Comments HR below 1 favors nintedanib
13.Secondary Outcome
Title Dose Normalised Predose Plasma Concentration at Steady State (Cpre,ss,Norm) of Nintedanib and of Its Metabolites BIBF 1202 and BIBF 1202 Glucuronide
Hide Description Geometric mean of dose normalised predose plasma concentration (Cpre,ss,norm) of nintedanib and of its metabolites BIBF 1202 and BIBF 1202 glucuronide evaluated at steady state based on course 2 and 3. If only one value was available and valid, then this value was used for calculation of Cpre,ss,norm.
Time Frame Before the administration of nintedanib or placebo and between a window of 30 mins to an hour after administration of trial drug during Course 2 and between 1 and 3 hours after administration of trial drug during Course 3
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Hide Analysis Population Description
Pharmacokinetic set- all patients in the treated set who were documented to have received at least 1 dose of nintedanib and who had at least 1 valid drug plasma concentration available
Arm/Group Title Nitedanib 200 mg Bid Plus Docetaxel Nintedanib 150 Bid mg Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Nintedanib 150 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 454 38
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL/mg
nintedanib Number Analyzed 453 participants 38 participants
0.0707
(77.7%)
0.106
(52.6%)
metabolite BIBF 1202 Number Analyzed 454 participants 38 participants
0.0907
(127%)
0.190
(152%)
metabolite BIBF 1202 glucuronide Number Analyzed 429 participants 33 participants
1.04
(153%)
1.94
(135%)
14.Secondary Outcome
Title Incidence and Intensity of Adverse Events
Hide Description

Incidence and intensity of adverse events according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. The worst CTCAE grade per patient is reported and MedDRA version 15.1 used.

Serious signs and symptoms of progressive disease were reported as an adverse event in analysis of this endpoint.

Time Frame From the first drug administration until 28 days after the last drug administration, up to 42 months
Hide Outcome Measure Data
Hide Analysis Population Description
Treated set- all randomised patients who were documented to have taken at least 1 dose of study medication . Patients were allocated to the treatment groups according to the treatment actually received.
Arm/Group Title Nitedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description:
Nintedanib 200 mg twice daily administered orally in a form of a soft gelatin capsule plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
Overall Number of Participants Analyzed 652 655
Measure Type: Number
Unit of Measure: % of participants
Grade 1 5.7 8.2
Grade 2 16.6 20.5
Grade 3 21.2 21.2
Grade 4 33.7 31.3
Grade 5 16.4 11.8
Time Frame From the first drug administration until 28 days after the last drug administration, up to 42 months
Adverse Event Reporting Description Number of participants at risk corresponds to all randomised patients who were documented to have taken at least 1 dose of study medication. Patients were allocated to the treatment groups according to the treatment actually received.
 
Arm/Group Title Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Hide Arm/Group Description Nintedanib 200 mg twice daily administered orally in the form of a soft gelatin capsule plus docetaxel 75 milligram (mg)/square meter (m2) once every 3 weeks administered via intravenous infusion over 1 hour (h). Placebo soft gelatin capsule matching that of nintedanib 2 times daily plus docetaxel 75 mg/m2 once every 3 weeks administered via intravenous infusion over 1 hour (h).
All-Cause Mortality
Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   107/652 (16.41%)   77/655 (11.76%) 
Hide Serious Adverse Events
Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   224/652 (34.36%)   206/655 (31.45%) 
Blood and lymphatic system disorders     
Anaemia  1  2/652 (0.31%)  6/655 (0.92%) 
Disseminated intravascular coagulation  1  1/652 (0.15%)  0/655 (0.00%) 
Febrile neutropenia  1  30/652 (4.60%)  19/655 (2.90%) 
Leukopenia  1  1/652 (0.15%)  2/655 (0.31%) 
Neutropenia  1  21/652 (3.22%)  21/655 (3.21%) 
Pancytopenia  1  2/652 (0.31%)  0/655 (0.00%) 
Thrombocytopenia  1  0/652 (0.00%)  2/655 (0.31%) 
Cardiac disorders     
Acute myocardial infarction  1  0/652 (0.00%)  1/655 (0.15%) 
Angina pectoris  1  0/652 (0.00%)  1/655 (0.15%) 
Atrial fibrillation  1  5/652 (0.77%)  2/655 (0.31%) 
Atrial flutter  1  1/652 (0.15%)  2/655 (0.31%) 
Atrioventricular block second degree  1  1/652 (0.15%)  0/655 (0.00%) 
Cardiac arrest  1  1/652 (0.15%)  0/655 (0.00%) 
Cardiac failure  1  0/652 (0.00%)  1/655 (0.15%) 
Cardiac failure acute  1  1/652 (0.15%)  2/655 (0.31%) 
Cardio-respiratory arrest  1  1/652 (0.15%)  2/655 (0.31%) 
Cardiopulmonary failure  1  1/652 (0.15%)  2/655 (0.31%) 
Coronary artery disease  1  0/652 (0.00%)  1/655 (0.15%) 
Myocardial infarction  1  1/652 (0.15%)  3/655 (0.46%) 
Pericardial effusion  1  4/652 (0.61%)  0/655 (0.00%) 
Pericarditis  1  1/652 (0.15%)  0/655 (0.00%) 
Tachyarrhythmia  1  2/652 (0.31%)  0/655 (0.00%) 
Ventricular arrhythmia  1  1/652 (0.15%)  0/655 (0.00%) 
Ear and labyrinth disorders     
Vertigo  1  0/652 (0.00%)  2/655 (0.31%) 
Eye disorders     
Diplopia  1  1/652 (0.15%)  0/655 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  2/652 (0.31%)  4/655 (0.61%) 
Abdominal pain upper  1  0/652 (0.00%)  2/655 (0.31%) 
Diarrhoea  1  16/652 (2.45%)  13/655 (1.98%) 
Diverticulum intestinal  1  1/652 (0.15%)  0/655 (0.00%) 
Duodenal ulcer haemorrhage  1  1/652 (0.15%)  0/655 (0.00%) 
Dysphagia  1  0/652 (0.00%)  2/655 (0.31%) 
Enteritis  1  1/652 (0.15%)  0/655 (0.00%) 
Gastric perforation  1  0/652 (0.00%)  1/655 (0.15%) 
Gastritis erosive  1  0/652 (0.00%)  1/655 (0.15%) 
Gastrointestinal necrosis  1  0/652 (0.00%)  1/655 (0.15%) 
Haematochezia  1  1/652 (0.15%)  0/655 (0.00%) 
Haemorrhoidal haemorrhage  1  0/652 (0.00%)  1/655 (0.15%) 
Intestinal obstruction  1  1/652 (0.15%)  0/655 (0.00%) 
Intestinal perforation  1  0/652 (0.00%)  1/655 (0.15%) 
Large intestine perforation  1  1/652 (0.15%)  1/655 (0.15%) 
Nausea  1  0/652 (0.00%)  1/655 (0.15%) 
Neutropenic colitis  1  1/652 (0.15%)  0/655 (0.00%) 
Pancreatitis  1  2/652 (0.31%)  0/655 (0.00%) 
Pancreatitis acute  1  1/652 (0.15%)  0/655 (0.00%) 
Stomatitis  1  1/652 (0.15%)  3/655 (0.46%) 
Vomiting  1  8/652 (1.23%)  7/655 (1.07%) 
General disorders     
Asthenia  1  7/652 (1.07%)  4/655 (0.61%) 
Chest discomfort  1  1/652 (0.15%)  1/655 (0.15%) 
Chest pain  1  7/652 (1.07%)  8/655 (1.22%) 
Condition aggravated  1  1/652 (0.15%)  0/655 (0.00%) 
Death  1  2/652 (0.31%)  1/655 (0.15%) 
Device occlusion  1  0/652 (0.00%)  1/655 (0.15%) 
Extravasation  1  0/652 (0.00%)  1/655 (0.15%) 
Fatigue  1  7/652 (1.07%)  1/655 (0.15%) 
Feeling abnormal  1  0/652 (0.00%)  1/655 (0.15%) 
General physical health deterioration  1  11/652 (1.69%)  8/655 (1.22%) 
Malaise  1  1/652 (0.15%)  0/655 (0.00%) 
Mucosal inflammation  1  1/652 (0.15%)  1/655 (0.15%) 
Multi-organ failure  1  2/652 (0.31%)  1/655 (0.15%) 
Oedema peripheral  1  1/652 (0.15%)  0/655 (0.00%) 
Organ failure  1  1/652 (0.15%)  0/655 (0.00%) 
Pain  1  1/652 (0.15%)  0/655 (0.00%) 
Performance status decreased  1  1/652 (0.15%)  0/655 (0.00%) 
Pyrexia  1  7/652 (1.07%)  9/655 (1.37%) 
Hepatobiliary disorders     
Bile duct obstruction  1  1/652 (0.15%)  1/655 (0.15%) 
Cholecystocholangitis  1  1/652 (0.15%)  0/655 (0.00%) 
Cholestasis  1  2/652 (0.31%)  1/655 (0.15%) 
Hepatic failure  1  1/652 (0.15%)  0/655 (0.00%) 
Hepatic function abnormal  1  1/652 (0.15%)  0/655 (0.00%) 
Jaundice cholestatic  1  1/652 (0.15%)  0/655 (0.00%) 
Immune system disorders     
Drug hypersensitivity  1  2/652 (0.31%)  2/655 (0.31%) 
Hypersensitivity  1  0/652 (0.00%)  3/655 (0.46%) 
Infections and infestations     
Abscess rupture  1  1/652 (0.15%)  0/655 (0.00%) 
Appendicitis  1  0/652 (0.00%)  1/655 (0.15%) 
Bronchitis  1  1/652 (0.15%)  4/655 (0.61%) 
Bronchopneumonia  1  0/652 (0.00%)  1/655 (0.15%) 
Cellulitis  1  1/652 (0.15%)  0/655 (0.00%) 
Empyema  1  1/652 (0.15%)  1/655 (0.15%) 
Erysipelas  1  1/652 (0.15%)  0/655 (0.00%) 
Febrile infection  1  0/652 (0.00%)  1/655 (0.15%) 
Folliculitis  1  1/652 (0.15%)  0/655 (0.00%) 
Gastroenteritis  1  0/652 (0.00%)  2/655 (0.31%) 
Gastrointestinal infection  1  1/652 (0.15%)  0/655 (0.00%) 
H1N1 influenza  1  0/652 (0.00%)  1/655 (0.15%) 
Infection  1  0/652 (0.00%)  2/655 (0.31%) 
Infectious pleural effusion  1  2/652 (0.31%)  1/655 (0.15%) 
Influenza  1  1/652 (0.15%)  0/655 (0.00%) 
Laryngitis  1  1/652 (0.15%)  0/655 (0.00%) 
Lower respiratory tract infection  1  4/652 (0.61%)  3/655 (0.46%) 
Lung abscess  1  1/652 (0.15%)  0/655 (0.00%) 
Lung infection  1  1/652 (0.15%)  0/655 (0.00%) 
Neutropenic infection  1  1/652 (0.15%)  0/655 (0.00%) 
Neutropenic sepsis  1  0/652 (0.00%)  1/655 (0.15%) 
Opportunistic infection  1  0/652 (0.00%)  1/655 (0.15%) 
Oral candidiasis  1  1/652 (0.15%)  0/655 (0.00%) 
Perirectal abscess  1  1/652 (0.15%)  0/655 (0.00%) 
Pharyngitis  1  2/652 (0.31%)  0/655 (0.00%) 
Pneumonia  1  17/652 (2.61%)  26/655 (3.97%) 
Pulmonary tuberculosis  1  0/652 (0.00%)  1/655 (0.15%) 
Respiratory tract infection  1  1/652 (0.15%)  3/655 (0.46%) 
Respiratory tract infection bacterial  1  0/652 (0.00%)  1/655 (0.15%) 
Sepsis  1  7/652 (1.07%)  3/655 (0.46%) 
Septic shock  1  2/652 (0.31%)  0/655 (0.00%) 
Streptococcal infection  1  0/652 (0.00%)  1/655 (0.15%) 
Tuberculosis  1  1/652 (0.15%)  0/655 (0.00%) 
Upper respiratory tract infection  1  1/652 (0.15%)  3/655 (0.46%) 
Urinary tract infection  1  1/652 (0.15%)  2/655 (0.31%) 
Injury, poisoning and procedural complications     
Acetabulum fracture  1  0/652 (0.00%)  1/655 (0.15%) 
Alcohol poisoning  1  0/652 (0.00%)  1/655 (0.15%) 
Femoral neck fracture  1  1/652 (0.15%)  0/655 (0.00%) 
Humerus fracture  1  0/652 (0.00%)  1/655 (0.15%) 
Post procedural haemorrhage  1  0/652 (0.00%)  1/655 (0.15%) 
Spinal compression fracture  1  1/652 (0.15%)  0/655 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  2/652 (0.31%)  0/655 (0.00%) 
Aspartate aminotransferase increased  1  2/652 (0.31%)  0/655 (0.00%) 
Blood creatinine increased  1  1/652 (0.15%)  1/655 (0.15%) 
Haemoglobin decreased  1  3/652 (0.46%)  2/655 (0.31%) 
Hepatic enzyme increased  1  1/652 (0.15%)  0/655 (0.00%) 
Liver function test abnormal  1  0/652 (0.00%)  1/655 (0.15%) 
Neutrophil count decreased  1  6/652 (0.92%)  3/655 (0.46%) 
Weight decreased  1  0/652 (0.00%)  1/655 (0.15%) 
White blood cell count decreased  1  3/652 (0.46%)  2/655 (0.31%) 
Metabolism and nutrition disorders     
Decreased appetite  1  1/652 (0.15%)  1/655 (0.15%) 
Dehydration  1  5/652 (0.77%)  1/655 (0.15%) 
Hypercalcaemia  1  1/652 (0.15%)  0/655 (0.00%) 
Hyperglycaemia  1  1/652 (0.15%)  1/655 (0.15%) 
Hyperuricaemia  1  1/652 (0.15%)  0/655 (0.00%) 
Hypoalbuminaemia  1  1/652 (0.15%)  0/655 (0.00%) 
Hypoglycaemia  1  1/652 (0.15%)  0/655 (0.00%) 
Hypokalaemia  1  1/652 (0.15%)  2/655 (0.31%) 
Hyponatraemia  1  4/652 (0.61%)  0/655 (0.00%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/652 (0.15%)  0/655 (0.00%) 
Bone pain  1  0/652 (0.00%)  2/655 (0.31%) 
Flank pain  1  1/652 (0.15%)  0/655 (0.00%) 
Haemarthrosis  1  0/652 (0.00%)  1/655 (0.15%) 
Muscular weakness  1  2/652 (0.31%)  0/655 (0.00%) 
Musculoskeletal chest pain  1  1/652 (0.15%)  0/655 (0.00%) 
Myalgia  1  0/652 (0.00%)  1/655 (0.15%) 
Pain in extremity  1  1/652 (0.15%)  1/655 (0.15%) 
Pathological fracture  1  1/652 (0.15%)  1/655 (0.15%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Hepatic cancer metastatic  1  1/652 (0.15%)  0/655 (0.00%) 
Malignant neoplasm progression  1  25/652 (3.83%)  17/655 (2.60%) 
Metastases to central nervous system  1  2/652 (0.31%)  2/655 (0.31%) 
Metastases to chest wall  1  1/652 (0.15%)  0/655 (0.00%) 
Metastases to kidney  1  0/652 (0.00%)  1/655 (0.15%) 
Metastases to meninges  1  3/652 (0.46%)  0/655 (0.00%) 
Metastases to skin  1  0/652 (0.00%)  1/655 (0.15%) 
Metastatic neoplasm  1  0/652 (0.00%)  1/655 (0.15%) 
Metastatic pain  1  0/652 (0.00%)  1/655 (0.15%) 
Tumour necrosis  1  0/652 (0.00%)  1/655 (0.15%) 
Tumour pain  1  1/652 (0.15%)  2/655 (0.31%) 
Nervous system disorders     
Aphasia  1  0/652 (0.00%)  1/655 (0.15%) 
Brain oedema  1  1/652 (0.15%)  2/655 (0.31%) 
Cerebral infarction  1  1/652 (0.15%)  0/655 (0.00%) 
Cerebrovascular accident  1  0/652 (0.00%)  2/655 (0.31%) 
Cognitive disorder  1  1/652 (0.15%)  0/655 (0.00%) 
Coma  1  1/652 (0.15%)  0/655 (0.00%) 
Convulsion  1  4/652 (0.61%)  0/655 (0.00%) 
Depressed level of consciousness  1  0/652 (0.00%)  1/655 (0.15%) 
Diplegia  1  1/652 (0.15%)  0/655 (0.00%) 
Dizziness  1  1/652 (0.15%)  2/655 (0.31%) 
Encephalopathy  1  0/652 (0.00%)  1/655 (0.15%) 
Epiduritis  1  0/652 (0.00%)  1/655 (0.15%) 
Facial paresis  1  1/652 (0.15%)  0/655 (0.00%) 
Headache  1  0/652 (0.00%)  1/655 (0.15%) 
Hemiplegia  1  0/652 (0.00%)  1/655 (0.15%) 
Hypoaesthesia  1  0/652 (0.00%)  1/655 (0.15%) 
Intracranial pressure increased  1  1/652 (0.15%)  2/655 (0.31%) 
Ischaemic stroke  1  1/652 (0.15%)  0/655 (0.00%) 
Lethargy  1  1/652 (0.15%)  0/655 (0.00%) 
Loss of consciousness  1  2/652 (0.31%)  0/655 (0.00%) 
Monoparesis  1  0/652 (0.00%)  1/655 (0.15%) 
Nervous system disorder  1  0/652 (0.00%)  1/655 (0.15%) 
Neuralgia  1  1/652 (0.15%)  0/655 (0.00%) 
Neuropathy peripheral  1  1/652 (0.15%)  0/655 (0.00%) 
Paraesthesia  1  1/652 (0.15%)  0/655 (0.00%) 
Paraparesis  1  0/652 (0.00%)  1/655 (0.15%) 
Restless legs syndrome  1  0/652 (0.00%)  1/655 (0.15%) 
Spinal cord compression  1  0/652 (0.00%)  2/655 (0.31%) 
Syncope  1  1/652 (0.15%)  2/655 (0.31%) 
Transient ischaemic attack  1  1/652 (0.15%)  2/655 (0.31%) 
Psychiatric disorders     
Confusional state  1  0/652 (0.00%)  2/655 (0.31%) 
Depression  1  4/652 (0.61%)  0/655 (0.00%) 
Disorientation  1  0/652 (0.00%)  3/655 (0.46%) 
Mental disorder due to a general medical condition  1  1/652 (0.15%)  1/655 (0.15%) 
Panic attack  1  1/652 (0.15%)  0/655 (0.00%) 
Personality change  1  1/652 (0.15%)  0/655 (0.00%) 
Psychotic disorder  1  0/652 (0.00%)  1/655 (0.15%) 
Renal and urinary disorders     
Bladder perforation  1  1/652 (0.15%)  0/655 (0.00%) 
Haematuria  1  1/652 (0.15%)  0/655 (0.00%) 
Renal failure acute  1  1/652 (0.15%)  1/655 (0.15%) 
Urinary incontinence  1  1/652 (0.15%)  0/655 (0.00%) 
Urinary retention  1  0/652 (0.00%)  2/655 (0.31%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  2/652 (0.31%)  0/655 (0.00%) 
Acute respiratory failure  1  3/652 (0.46%)  1/655 (0.15%) 
Alveolitis  1  1/652 (0.15%)  0/655 (0.00%) 
Atelectasis  1  2/652 (0.31%)  1/655 (0.15%) 
Bronchial haemorrhage  1  1/652 (0.15%)  0/655 (0.00%) 
Bronchial secretion retention  1  0/652 (0.00%)  1/655 (0.15%) 
Bronchostenosis  1  1/652 (0.15%)  1/655 (0.15%) 
Chronic obstructive pulmonary disease  1  1/652 (0.15%)  2/655 (0.31%) 
Cough  1  3/652 (0.46%)  2/655 (0.31%) 
Dysphonia  1  1/652 (0.15%)  0/655 (0.00%) 
Dyspnoea  1  24/652 (3.68%)  30/655 (4.58%) 
Haemoptysis  1  6/652 (0.92%)  7/655 (1.07%) 
Hypoxia  1  1/652 (0.15%)  0/655 (0.00%) 
Interstitial lung disease  1  1/652 (0.15%)  0/655 (0.00%) 
Lung disorder  1  1/652 (0.15%)  1/655 (0.15%) 
Lung infiltration  1  0/652 (0.00%)  1/655 (0.15%) 
Obstructive airways disorder  1  1/652 (0.15%)  0/655 (0.00%) 
Oropharyngeal pain  1  0/652 (0.00%)  1/655 (0.15%) 
Pleural effusion  1  8/652 (1.23%)  8/655 (1.22%) 
Pleuritic pain  1  1/652 (0.15%)  0/655 (0.00%) 
Pneumonitis  1  1/652 (0.15%)  0/655 (0.00%) 
Pneumothorax  1  3/652 (0.46%)  1/655 (0.15%) 
Pulmonary embolism  1  4/652 (0.61%)  6/655 (0.92%) 
Pulmonary fibrosis  1  1/652 (0.15%)  0/655 (0.00%) 
Pulmonary haemorrhage  1  5/652 (0.77%)  3/655 (0.46%) 
Respiratory depression  1  0/652 (0.00%)  1/655 (0.15%) 
Respiratory failure  1  8/652 (1.23%)  2/655 (0.31%) 
Stridor  1  0/652 (0.00%)  1/655 (0.15%) 
Tracheal stenosis  1  0/652 (0.00%)  1/655 (0.15%) 
Vascular disorders     
Circulatory collapse  1  0/652 (0.00%)  1/655 (0.15%) 
Deep vein thrombosis  1  3/652 (0.46%)  1/655 (0.15%) 
Haemorrhage  1  1/652 (0.15%)  2/655 (0.31%) 
Hypotension  1  3/652 (0.46%)  1/655 (0.15%) 
Peripheral ischaemia  1  0/652 (0.00%)  1/655 (0.15%) 
Subclavian artery thrombosis  1  0/652 (0.00%)  1/655 (0.15%) 
Superior vena cava syndrome  1  1/652 (0.15%)  1/655 (0.15%) 
Thrombosis  1  0/652 (0.00%)  1/655 (0.15%) 
Venous thrombosis  1  1/652 (0.15%)  0/655 (0.00%) 
Venous thrombosis limb  1  1/652 (0.15%)  0/655 (0.00%) 
1
Term from vocabulary, MedDRA 15.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Nintedanib Plus Docetaxel Placebo Plus Docetaxel
Affected / at Risk (%) Affected / at Risk (%)
Total   569/652 (87.27%)   547/655 (83.51%) 
Blood and lymphatic system disorders     
Anaemia  1  33/652 (5.06%)  43/655 (6.56%) 
Neutropenia  1  69/652 (10.58%)  73/655 (11.15%) 
Gastrointestinal disorders     
Abdominal pain  1  35/652 (5.37%)  37/655 (5.65%) 
Constipation  1  35/652 (5.37%)  76/655 (11.60%) 
Diarrhoea  1  260/652 (39.88%)  130/655 (19.85%) 
Nausea  1  158/652 (24.23%)  117/655 (17.86%) 
Stomatitis  1  62/652 (9.51%)  54/655 (8.24%) 
Vomiting  1  102/652 (15.64%)  54/655 (8.24%) 
General disorders     
Asthenia  1  51/652 (7.82%)  60/655 (9.16%) 
Chest pain  1  49/652 (7.52%)  54/655 (8.24%) 
Fatigue  1  191/652 (29.29%)  175/655 (26.72%) 
Oedema peripheral  1  35/652 (5.37%)  42/655 (6.41%) 
Pyrexia  1  76/652 (11.66%)  89/655 (13.59%) 
Investigations     
Alanine aminotransferase increased  1  184/652 (28.22%)  55/655 (8.40%) 
Aspartate aminotransferase increased  1  145/652 (22.24%)  43/655 (6.56%) 
Blood alkaline phosphatase increased  1  38/652 (5.83%)  9/655 (1.37%) 
Haemoglobin decreased  1  70/652 (10.74%)  77/655 (11.76%) 
Neutrophil count decreased  1  236/652 (36.20%)  232/655 (35.42%) 
White blood cell count decreased  1  157/652 (24.08%)  158/655 (24.12%) 
Metabolism and nutrition disorders     
Decreased appetite  1  144/652 (22.09%)  101/655 (15.42%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  40/652 (6.13%)  46/655 (7.02%) 
Back pain  1  26/652 (3.99%)  44/655 (6.72%) 
Myalgia  1  40/652 (6.13%)  45/655 (6.87%) 
Pain in extremity  1  31/652 (4.75%)  41/655 (6.26%) 
Nervous system disorders     
Dizziness  1  31/652 (4.75%)  34/655 (5.19%) 
Dysgeusia  1  31/652 (4.75%)  34/655 (5.19%) 
Headache  1  39/652 (5.98%)  42/655 (6.41%) 
Peripheral sensory neuropathy  1  40/652 (6.13%)  47/655 (7.18%) 
Psychiatric disorders     
Insomnia  1  31/652 (4.75%)  38/655 (5.80%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  96/652 (14.72%)  108/655 (16.49%) 
Dyspnoea  1  100/652 (15.34%)  80/655 (12.21%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  107/652 (16.41%)  119/655 (18.17%) 
1
Term from vocabulary, MedDRA 15.1
Indicates events were collected by systematic assessment
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 Pharmaceuticals
Phone: 1-800-243-0127
EMail: clintriage.rdg@boehringer-ingelheim.com
Layout table for additonal information
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00805194    
Other Study ID Numbers: 1199.13
2007-004803-36 ( EudraCT Number )
First Submitted: December 8, 2008
First Posted: December 9, 2008
Results First Submitted: November 14, 2014
Results First Posted: December 1, 2014
Last Update Posted: December 5, 2018