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BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)

Primary Purpose

Carcinoma, Non-Small-Cell Lung, Adenocarcinoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Gemcitabine+Cisplatin
BIBW 2992
Sponsored by
Boehringer Ingelheim
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Carcinoma, Non-Small-Cell Lung

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria:

  1. pathologically confirmed diagnosis of stage IIIB or stage IV adenocarcinoma of the Lung
  2. EGFR(Epidermal Growth Factor Receptor) mutation detected by central laboratory analysis of tumor biopsy material
  3. Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST)1.1
  4. Eastern Cooperative Oncology Group (ECOG) score of 0 or 1.
  5. Age>=18 years
  6. life expectancy of at least three months
  7. Written informed consent that is consistent with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guidelines.

Exclusion criteria:

  1. Prior chemotherapy for relapsed and/or metastatic NSCLC.
  2. Prior treatment with EGFR targeting small molecules or antibodies.
  3. Radiotherapy or surgery(other than biopsy) within 4 weeks prior to randomization
  4. Active brain metastases
  5. Any other current malignancy or malignancy diagnosed within the past 5 years
  6. Known pre-existing interstitial lung disease
  7. Significant or recent acute gastrointestinal disorders with diarrhoea as a a major symptoms.
  8. History or presence of clinically relevant cardiovascular abnormalities
  9. Cardiac left ventricular function with resting ejection fraction of less than 50%.
  10. Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
  11. Absolute neutrophil count(ANC)<1500/mm3
  12. Platelet count<100,000/mm3
  13. Creatinine clearance<60ml/min or serum creatinine>1.5 times Upper Limit of Normal (ULN).
  14. Bilirubin>1.5 times ULN
  15. Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) > 3 times ULN
  16. Women of childbearing potential, or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial
  17. Pregnancy of breast-feeding
  18. Patients unable to comply with the protocol
  19. Active hepatitis B infection, active hepatitis C infection or known HIV(Human Immunodeficiency Virus) carrier.
  20. Known or suspected active drug or alcohol abuse.
  21. requirement for treatment with any of the prohibited concomitant medications listed in section 4.2.2
  22. Any contraindications for therapy with gemcitabine/cisplatin
  23. Known hypersensitivity to BIBW2992 or the excipient of any of the trial drugs
  24. Use of any investigational drug within 4 weeks of randomization.

Sites / Locations

  • Beijing Chao-Yang Hospital
  • 307 Hospital of PLA
  • Peking Union Medical College Hospital
  • Beijing Chest Hospital
  • First Hospital of Jilin University
  • Xiangya Hospital, Central South University
  • Hunan Province Tumor Hospital
  • West China Hospital
  • Fujian Provincial Tumor Hospital
  • Guangdong General Hospital
  • Guangzhou Institute of Respiratory Disease
  • NanFang Hosptial
  • The Third Affiliated Hospital of Harbin Medical University
  • Zhejiang Cancer Hospital
  • Hubei Cancer Hospital
  • Yunnan Provincial Tumor Hospital
  • Lin Yi Tumor Hospital
  • The Affiliated Cancer Hospital, Guangxi Medical University
  • the 81th Hospital of PLA
  • Jiangsu Cancer Hospital
  • The affiliated hospital of medicalcollege qingdao university
  • Shanghai Changzheng Hospital
  • Shanghai Chest Hospital
  • Zhongshan Hospital Fudan University
  • Shanghai Pulmonary Hospital
  • Changhai Hospital
  • The First Hospital of Chinese Medical University
  • Hebei Provincial Tumor Hospital
  • Tangdu Hospital
  • Northern Jiangsu People's Hospital
  • Kosin University Gospel Hospital
  • Chungbuk National University Hospital
  • Yeungnam University Medical Center
  • Konkuk University Medical Center
  • Korea University Guro Hospital
  • Songklanagarind Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm A BIBW 2992

Arm B Chemotherapy

Arm Description

Patients receive a tablet of BIBW 2992 daily until progression or unacceptable toxicity

Patients receive Gemcitabine and Cisplatin, maximum is 6 courses

Outcomes

Primary Outcome Measures

Progression-free Survival
The primary endpoint was progression-free survival (PFS) as assessed by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Progression-free survival was defined as the time from randomisation to disease progression or death whichever occurs earlier. A pre-defined set of censoring rules were used for patients who did not have a PFS. Only data collected up until the analysis cut-off date (27 December 2013) were considered. Median time results from unstratified Kaplan-Meier estimates.

Secondary Outcome Measures

Objective Response (OR)
OR is defined as a best overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1 and will be presented as the percentage of patients with OR. CR is defined as the disappearance of all target lesions and non-target lesions and no new lesions. PR is defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD, non-Progressive Disease or non evaluation of all non-target lesions and no new lesions. (Exact 95% Confidence interval by Clopper and Pearson.)
Disease Control (DC)
DC is defined as a patient with objective response (OR) or stable disease (SD) assessed by central independent review according to RECIST version 1.1 and will be presented as the percentage of patients with DC.
Overall Survival (OS)
OS is defined as the time from randomisation to death. For patients who had not died until 7 December 2017, the date they were last known to be alive was derived from patient status records, the trial completion record, radiological imaging assessments, the study treatment termination record, and the randomisation date. Median time results from unstratified Kaplan-Meier estimates.
Time to Objective Response (OR)
OR is defined as a best of overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1. For patients with an objective response, time to objective response was defined as the time from randomisation to the first objective response. Outcome data are the percentage of patients with OR by each scheduled tumour assessment.
Duration of Objective Response
OR is defined as a best of overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1. For patients with an objective response, duration of objective response was defined as the time from the first objective response to disease progression or death whichever occurs earlier. A pre-defined set of censoring rules were used for patients who did not progress/die. The Median values are Kaplan-Meier estimates.
Duration of Disease Control
For patients with disease control, duration of disease control was defined as the time from randomisation to progression or death whichever occurs first. A pre-defined set of censoring rules were used for patients who did not progress/die. The Median values are Kaplan-Meier estimates.
Tumour Shrinkage
Tumour shrinkage is calculated as the minimum post-baseline sum of longest diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) (SLD), as assessed by central independent review. The mean of these minimum values are presented after adjusting for baseline sum of longest diameters and EGFR mutation category. Only data collected up until the analysis cut-off date (27 Dec 2013) were considered. A negative value means the smallest post-baseline SLD was smaller than baseline (decreased since baseline); a positive value means tumor size increased since baseline. The means are adjusted for baseline sum of lesions and EGFR mutation category.
Change From Baseline in Body Weight
The change from baseline to the lowest and the last body weight recorded or during the the study.
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
The last ECOG performance score category recorded during the study. Outcome data are the percentage of patients with an shift of ECOG performance status from baseline to the last ECOG performance status. 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; Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work; Ambulatory (>50 percent of waking hours), capable of all selfcare, unable to carry out any work activities; Capable of only limited self care, confined to bed or chair more then 50 percent of waking hours; Completely disabled, cannot carry on any selfcare, totally confined to bed or chair; Dead
Health Related Quality of Life (HRQOL): Time of Deterioration in Coughing
HRQOL as measured by standardised questionnaires (EuropeanOrganisation for Research and Treatment of Cancer (EORTC)) quality of life questionaires (OLQ-C30) and its lung cancer module (QLQ-LC13). Analysis for cough: QLQ-LC13, question 1. Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. The median is Kaplan-Meier estimates.
Health Related Quality of Life (HRQOL): Time of Deterioration in Dyspnoea
HRQOL as measured by OLQ-C30 and its lung cancer module (QLQ-LC13). Analysis for dyspnoea: composite of QLQ-LC13, questions 3 to 5; individual item from QLQ-C30, question 8. Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. The median is Kaplan-Meier estimates.
Health Related Quality of Life (HRQOL): Time of Deterioration in Pain
HRQOL as measured by OLQ-C30 and its lung cancer module QLQ-LC13. Analysis for pain: composite of QLQ-C30, questions 9 and 19; individual items from QLQ-LC13, questions 10, 11 and 12. Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. The median is Kaplan-Meier estimates.
Pharmacokinetics of Afatinib at Day 22
Outcome data are the trough plasma concentrations of afatinib at day 22 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the Pharmacokinetics (PK) assessment period).
Pharmacokinetics of Afatinib at Day 29
Outcome data are the trough plasma concentrations of afatinib at day 29 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the PK assessment period).
Pharmacokinetics of Afatinib at Day 43
Outcome data are the trough plasma concentrations of afatinib at day 43 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the PK assessment period).
Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events
Safety of Afatinib as indicated by intensity and incidence of adverse events graded according to the US National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Presented as the percentage of patients with an Adverse Events during the on-treatment period by highest CTCAE grade.
Changes in Safety Laboratory Parameters
Outcome data presented are the percentage of patients by worst CTCAE grade (only Grades 2 to 4 presented) on treatment for the following laboratory parameters: Potassium, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Creatine and Creatine Kinase. For Potassium; only CTCAE grades resulting from hypokalemia (low values) are presented.

Full Information

First Posted
April 21, 2010
Last Updated
December 13, 2018
Sponsor
Boehringer Ingelheim
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1. Study Identification

Unique Protocol Identification Number
NCT01121393
Brief Title
BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)
Official Title
LUX-Lung 6: A Randomized, Open-label, Phase III Study of BIBW 2992 Versus Chemotherapy as First-line Treatment for Patients With Stage IIIB or IV Adenocarcinoma of the Lung Harbouring an EGFR Activating Mutation
Study Type
Interventional

2. Study Status

Record Verification Date
December 2018
Overall Recruitment Status
Completed
Study Start Date
April 19, 2010 (Actual)
Primary Completion Date
November 23, 2017 (Actual)
Study Completion Date
November 26, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Boehringer Ingelheim

4. Oversight

5. Study Description

Brief Summary
To investigate the efficacy and safety of BIBW 2992 compared to standard first-line chemotherapy in patients with stage IIIB or IV adenocarcinoma of the lung harbouring an EGFR activating mutation

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non-Small-Cell Lung, Adenocarcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
364 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A BIBW 2992
Arm Type
Experimental
Arm Description
Patients receive a tablet of BIBW 2992 daily until progression or unacceptable toxicity
Arm Title
Arm B Chemotherapy
Arm Type
Active Comparator
Arm Description
Patients receive Gemcitabine and Cisplatin, maximum is 6 courses
Intervention Type
Drug
Intervention Name(s)
Gemcitabine+Cisplatin
Intervention Description
Gemcitabine d1,8, Cisplatin d1, 21 days as a course, up to 6 courses.
Intervention Type
Drug
Intervention Name(s)
BIBW 2992
Intervention Description
starting dose is 40 mg, in the event of no or minimal drug-related adverse events after one course, the dose will be increased to 50mg. in the event of certain drug related Adverse Event (AE), dose reduction will be increments of 10 mg, with the lowest dose being 20mg.
Primary Outcome Measure Information:
Title
Progression-free Survival
Description
The primary endpoint was progression-free survival (PFS) as assessed by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Progression-free survival was defined as the time from randomisation to disease progression or death whichever occurs earlier. A pre-defined set of censoring rules were used for patients who did not have a PFS. Only data collected up until the analysis cut-off date (27 December 2013) were considered. Median time results from unstratified Kaplan-Meier estimates.
Time Frame
Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 168
Secondary Outcome Measure Information:
Title
Objective Response (OR)
Description
OR is defined as a best overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1 and will be presented as the percentage of patients with OR. CR is defined as the disappearance of all target lesions and non-target lesions and no new lesions. PR is defined as at least a 30% decrease in the sum of longest diameter (LD) of target lesions taking as reference the baseline sum LD, non-Progressive Disease or non evaluation of all non-target lesions and no new lesions. (Exact 95% Confidence interval by Clopper and Pearson.)
Time Frame
Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374
Title
Disease Control (DC)
Description
DC is defined as a patient with objective response (OR) or stable disease (SD) assessed by central independent review according to RECIST version 1.1 and will be presented as the percentage of patients with DC.
Time Frame
Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374
Title
Overall Survival (OS)
Description
OS is defined as the time from randomisation to death. For patients who had not died until 7 December 2017, the date they were last known to be alive was derived from patient status records, the trial completion record, radiological imaging assessments, the study treatment termination record, and the randomisation date. Median time results from unstratified Kaplan-Meier estimates.
Time Frame
From randomisation up to 374 weeks
Title
Time to Objective Response (OR)
Description
OR is defined as a best of overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1. For patients with an objective response, time to objective response was defined as the time from randomisation to the first objective response. Outcome data are the percentage of patients with OR by each scheduled tumour assessment.
Time Frame
Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374
Title
Duration of Objective Response
Description
OR is defined as a best of overall response of complete response (CR) or partial response (PR) assessed by central independent review according to RECIST version 1.1. For patients with an objective response, duration of objective response was defined as the time from the first objective response to disease progression or death whichever occurs earlier. A pre-defined set of censoring rules were used for patients who did not progress/die. The Median values are Kaplan-Meier estimates.
Time Frame
Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374
Title
Duration of Disease Control
Description
For patients with disease control, duration of disease control was defined as the time from randomisation to progression or death whichever occurs first. A pre-defined set of censoring rules were used for patients who did not progress/die. The Median values are Kaplan-Meier estimates.
Time Frame
Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374
Title
Tumour Shrinkage
Description
Tumour shrinkage is calculated as the minimum post-baseline sum of longest diameters of target lesions (longest for non-nodal lesions, short axis for nodal lesions) (SLD), as assessed by central independent review. The mean of these minimum values are presented after adjusting for baseline sum of longest diameters and EGFR mutation category. Only data collected up until the analysis cut-off date (27 Dec 2013) were considered. A negative value means the smallest post-baseline SLD was smaller than baseline (decreased since baseline); a positive value means tumor size increased since baseline. The means are adjusted for baseline sum of lesions and EGFR mutation category.
Time Frame
Tumour assessment were performed at screening, week 6, 12, 18, 24, 30, 36, 42, 48 and then every 12 weeks until progression or death whichever occurs first up to week 374
Title
Change From Baseline in Body Weight
Description
The change from baseline to the lowest and the last body weight recorded or during the the study.
Time Frame
Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
Title
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Description
The last ECOG performance score category recorded during the study. Outcome data are the percentage of patients with an shift of ECOG performance status from baseline to the last ECOG performance status. 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; Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work; Ambulatory (>50 percent of waking hours), capable of all selfcare, unable to carry out any work activities; Capable of only limited self care, confined to bed or chair more then 50 percent of waking hours; Completely disabled, cannot carry on any selfcare, totally confined to bed or chair; Dead
Time Frame
Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
Title
Health Related Quality of Life (HRQOL): Time of Deterioration in Coughing
Description
HRQOL as measured by standardised questionnaires (EuropeanOrganisation for Research and Treatment of Cancer (EORTC)) quality of life questionaires (OLQ-C30) and its lung cancer module (QLQ-LC13). Analysis for cough: QLQ-LC13, question 1. Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. The median is Kaplan-Meier estimates.
Time Frame
Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
Title
Health Related Quality of Life (HRQOL): Time of Deterioration in Dyspnoea
Description
HRQOL as measured by OLQ-C30 and its lung cancer module (QLQ-LC13). Analysis for dyspnoea: composite of QLQ-LC13, questions 3 to 5; individual item from QLQ-C30, question 8. Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. The median is Kaplan-Meier estimates.
Time Frame
Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
Title
Health Related Quality of Life (HRQOL): Time of Deterioration in Pain
Description
HRQOL as measured by OLQ-C30 and its lung cancer module QLQ-LC13. Analysis for pain: composite of QLQ-C30, questions 9 and 19; individual items from QLQ-LC13, questions 10, 11 and 12. Time to deterioration was defined as the time from randomisation to a score increase (i.e. worsened) of at least 10 points from baseline (0 to 100 point scale). Patients without deterioration (including those with disease progression) were censored at the date of the last available HRQOL assessment; patients without post-baseline assessments were censored at the date of randomisation. Patients were considered as having deteriorated at the time of death. The median is Kaplan-Meier estimates.
Time Frame
Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
Title
Pharmacokinetics of Afatinib at Day 22
Description
Outcome data are the trough plasma concentrations of afatinib at day 22 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the Pharmacokinetics (PK) assessment period).
Time Frame
Day 22 (course 2, visit 1)
Title
Pharmacokinetics of Afatinib at Day 29
Description
Outcome data are the trough plasma concentrations of afatinib at day 29 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the PK assessment period).
Time Frame
Day 29 (course 2, visit 2)
Title
Pharmacokinetics of Afatinib at Day 43
Description
Outcome data are the trough plasma concentrations of afatinib at day 43 after multiple daily dosing of 40mg afatinib and after dose escalation to 50mg or dose reduction to 30mg afatinib (no patient dose reduced to 20mg during the PK assessment period).
Time Frame
Day 43 (course 3, visit 1)
Title
Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events
Description
Safety of Afatinib as indicated by intensity and incidence of adverse events graded according to the US National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Presented as the percentage of patients with an Adverse Events during the on-treatment period by highest CTCAE grade.
Time Frame
From first administration of study medication up to 28 days after the last administration of study medication up to 374 weeks.
Title
Changes in Safety Laboratory Parameters
Description
Outcome data presented are the percentage of patients by worst CTCAE grade (only Grades 2 to 4 presented) on treatment for the following laboratory parameters: Potassium, Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Creatine and Creatine Kinase. For Potassium; only CTCAE grades resulting from hypokalemia (low values) are presented.
Time Frame
From first administration of study medication up to 28 days after the last administration of study medication up to 374 weeks.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria: pathologically confirmed diagnosis of stage IIIB or stage IV adenocarcinoma of the Lung EGFR(Epidermal Growth Factor Receptor) mutation detected by central laboratory analysis of tumor biopsy material Measurable disease according to Response Evaluation Criteria in Solid Tumours (RECIST)1.1 Eastern Cooperative Oncology Group (ECOG) score of 0 or 1. Age>=18 years life expectancy of at least three months Written informed consent that is consistent with International Conference on Harmonisation-Good Clinical Practice (ICH-GCP) guidelines. Exclusion criteria: Prior chemotherapy for relapsed and/or metastatic NSCLC. Prior treatment with EGFR targeting small molecules or antibodies. Radiotherapy or surgery(other than biopsy) within 4 weeks prior to randomization Active brain metastases Any other current malignancy or malignancy diagnosed within the past 5 years Known pre-existing interstitial lung disease Significant or recent acute gastrointestinal disorders with diarrhoea as a a major symptoms. History or presence of clinically relevant cardiovascular abnormalities Cardiac left ventricular function with resting ejection fraction of less than 50%. Any other concomitant serious illness or organ system dysfunction which in the opinion of the investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug. Absolute neutrophil count(ANC)<1500/mm3 Platelet count<100,000/mm3 Creatinine clearance<60ml/min or serum creatinine>1.5 times Upper Limit of Normal (ULN). Bilirubin>1.5 times ULN Aspartate Amino Transferase (AST) or Alanine Amino Transferase (ALT) > 3 times ULN Women of childbearing potential, or men who are able to father a child, unwilling to use a medically acceptable method of contraception during the trial Pregnancy of breast-feeding Patients unable to comply with the protocol Active hepatitis B infection, active hepatitis C infection or known HIV(Human Immunodeficiency Virus) carrier. Known or suspected active drug or alcohol abuse. requirement for treatment with any of the prohibited concomitant medications listed in section 4.2.2 Any contraindications for therapy with gemcitabine/cisplatin Known hypersensitivity to BIBW2992 or the excipient of any of the trial drugs Use of any investigational drug within 4 weeks of randomization.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Boehringer Ingelheim
Organizational Affiliation
Boehringer Ingelheim
Official's Role
Study Chair
Facility Information:
Facility Name
Beijing Chao-Yang Hospital
City
Beijing
ZIP/Postal Code
100020
Country
China
Facility Name
307 Hospital of PLA
City
Beijing
ZIP/Postal Code
100071
Country
China
Facility Name
Peking Union Medical College Hospital
City
Beijing
ZIP/Postal Code
100730
Country
China
Facility Name
Beijing Chest Hospital
City
Beijing
ZIP/Postal Code
101149
Country
China
Facility Name
First Hospital of Jilin University
City
Changchun
ZIP/Postal Code
130021
Country
China
Facility Name
Xiangya Hospital, Central South University
City
Changsha
ZIP/Postal Code
410008
Country
China
Facility Name
Hunan Province Tumor Hospital
City
Changsha
Country
China
Facility Name
West China Hospital
City
Chengdu
ZIP/Postal Code
610041
Country
China
Facility Name
Fujian Provincial Tumor Hospital
City
Fuzhou
ZIP/Postal Code
350014
Country
China
Facility Name
Guangdong General Hospital
City
Guangzhou
ZIP/Postal Code
510080
Country
China
Facility Name
Guangzhou Institute of Respiratory Disease
City
Guangzhou
ZIP/Postal Code
510120
Country
China
Facility Name
NanFang Hosptial
City
Guangzhou
ZIP/Postal Code
510515
Country
China
Facility Name
The Third Affiliated Hospital of Harbin Medical University
City
Haerbin
ZIP/Postal Code
150081
Country
China
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
ZIP/Postal Code
310022
Country
China
Facility Name
Hubei Cancer Hospital
City
HongShan
Country
China
Facility Name
Yunnan Provincial Tumor Hospital
City
Kunming
ZIP/Postal Code
650118
Country
China
Facility Name
Lin Yi Tumor Hospital
City
Linyi
ZIP/Postal Code
276001
Country
China
Facility Name
The Affiliated Cancer Hospital, Guangxi Medical University
City
Nan Ning
Country
China
Facility Name
the 81th Hospital of PLA
City
Nanjing
ZIP/Postal Code
210002
Country
China
Facility Name
Jiangsu Cancer Hospital
City
Nanjing
ZIP/Postal Code
210009
Country
China
Facility Name
The affiliated hospital of medicalcollege qingdao university
City
Qingdao
ZIP/Postal Code
266101
Country
China
Facility Name
Shanghai Changzheng Hospital
City
Shanghai
ZIP/Postal Code
200003
Country
China
Facility Name
Shanghai Chest Hospital
City
Shanghai
ZIP/Postal Code
200030
Country
China
Facility Name
Zhongshan Hospital Fudan University
City
Shanghai
ZIP/Postal Code
200032
Country
China
Facility Name
Shanghai Pulmonary Hospital
City
Shanghai
ZIP/Postal Code
200433
Country
China
Facility Name
Changhai Hospital
City
Shanghai
ZIP/Postal Code
200443
Country
China
Facility Name
The First Hospital of Chinese Medical University
City
Shenyang
ZIP/Postal Code
110001
Country
China
Facility Name
Hebei Provincial Tumor Hospital
City
Shijiazhuang
Country
China
Facility Name
Tangdu Hospital
City
Xi'An
ZIP/Postal Code
710038
Country
China
Facility Name
Northern Jiangsu People's Hospital
City
Yangzhou
ZIP/Postal Code
225001
Country
China
Facility Name
Kosin University Gospel Hospital
City
Busan
ZIP/Postal Code
602-702
Country
Korea, Republic of
Facility Name
Chungbuk National University Hospital
City
Cheongju
ZIP/Postal Code
361711
Country
Korea, Republic of
Facility Name
Yeungnam University Medical Center
City
Daegu
ZIP/Postal Code
705-717
Country
Korea, Republic of
Facility Name
Konkuk University Medical Center
City
Seoul
ZIP/Postal Code
143-729
Country
Korea, Republic of
Facility Name
Korea University Guro Hospital
City
Seoul
ZIP/Postal Code
152-703
Country
Korea, Republic of
Facility Name
Songklanagarind Hospital
City
Songkla
ZIP/Postal Code
90110
Country
Thailand

12. IPD Sharing Statement

Citations:
PubMed Identifier
30584317
Citation
Wu YL, Xu CR, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Marten A, Fan J, Peil B, Zhou C. Afatinib versus gemcitabine/cisplatin for first-line treatment of Chinese patients with advanced non-small-cell lung cancer harboring EGFR mutations: subgroup analysis of the LUX-Lung 6 trial. Onco Targets Ther. 2018 Nov 30;11:8575-8587. doi: 10.2147/OTT.S160358. eCollection 2018.
Results Reference
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PubMed Identifier
29653820
Citation
Wu YL, Sequist LV, Tan EH, Geater SL, Orlov S, Zhang L, Lee KH, Tsai CM, Kato T, Barrios CH, Schuler M, Hirsh V, Yamamoto N, O'Byrne K, Boyer M, Mok T, Peil B, Marten A, Chih-Hsin Yang J, Paz-Ares L, Park K. Afatinib as First-line Treatment of Older Patients With EGFR Mutation-Positive Non-Small-Cell Lung Cancer: Subgroup Analyses of the LUX-Lung 3, LUX-Lung 6, and LUX-Lung 7 Trials. Clin Lung Cancer. 2018 Jul;19(4):e465-e479. doi: 10.1016/j.cllc.2018.03.009. Epub 2018 Mar 17.
Results Reference
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PubMed Identifier
27601237
Citation
Yang JC, Sequist LV, Zhou C, Schuler M, Geater SL, Mok T, Hu CP, Yamamoto N, Feng J, O'Byrne K, Lu S, Hirsh V, Huang Y, Sebastian M, Okamoto I, Dickgreber N, Shah R, Marten A, Massey D, Wind S, Wu YL. Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials. Ann Oncol. 2016 Nov;27(11):2103-2110. doi: 10.1093/annonc/mdw322. Epub 2016 Sep 6.
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PubMed Identifier
26823294
Citation
Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-Line Afatinib versus Chemotherapy in Patients with Non-Small Cell Lung Cancer and Common Epidermal Growth Factor Receptor Gene Mutations and Brain Metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. doi: 10.1016/j.jtho.2015.11.014. Epub 2016 Jan 25.
Results Reference
derived
PubMed Identifier
26051236
Citation
Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. doi: 10.1016/S1470-2045(15)00026-1. Epub 2015 Jun 4.
Results Reference
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PubMed Identifier
25589191
Citation
Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. doi: 10.1016/S1470-2045(14)71173-8. Epub 2015 Jan 12.
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PubMed Identifier
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Citation
Wu YL, Zhou C, Hu CP, Feng J, Lu S, Huang Y, Li W, Hou M, Shi JH, Lee KY, Xu CR, Massey D, Kim M, Shi Y, Geater SL. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Feb;15(2):213-22. doi: 10.1016/S1470-2045(13)70604-1. Epub 2014 Jan 15.
Results Reference
derived
Links:
URL
http://trials.boehringer-ingelheim.com
Description
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BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)

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