TriangleNCT01121393 · CITED IN SOURCE DOCUMENTS
BIBW 2992 (Afatinib) vs Gemcitabine-cisplatin in 1st Line Non-small Cell Lung Cancer (NSCLC)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2018-12-14
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
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-free Survival
Objective Response (OR)
Disease Control (DC)
Overall Survival (OS)
Time to Objective Response (OR)
Duration of Objective Response
Duration of Disease Control
Tumour Shrinkage
Change From Baseline in Body Weight
Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Health Related Quality of Life (HRQOL): Time of Deterioration in Coughing
Health Related Quality of Life (HRQOL): Time of Deterioration in Dyspnoea
Health Related Quality of Life (HRQOL): Time of Deterioration in Pain
Pharmacokinetics of Afatinib at Day 22
Pharmacokinetics of Afatinib at Day 29
Pharmacokinetics of Afatinib at Day 43
Safety of Afatinib as Indicated by Intensity and Incidence of Adverse Events
Changes in Safety Laboratory Parameters
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- 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.
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Patients receive a tablet of BIBW 2992 daily until progression or unacceptable toxicity
- intervention Names
- Drug: BIBW 2992
- label
- Arm A BIBW 2992
- type
- EXPERIMENTAL
- description
- Patients receive Gemcitabine and Cisplatin, maximum is 6 courses
- intervention Names
- Drug: Gemcitabine+Cisplatin
- label
- Arm B Chemotherapy
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- Arm B Chemotherapy
- description
- Gemcitabine d1,8, Cisplatin d1, 21 days as a course, up to 6 courses.
- name
- Gemcitabine+Cisplatin
- type
- DRUG
- arm Group Labels
- Arm A BIBW 2992
- 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.
- name
- BIBW 2992
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 364
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- 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.
- measure
- Progression-free Survival
- 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 Outcomes
- 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.)
- measure
- Objective Response (OR)
- 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
- 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.
- measure
- Disease Control (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
- 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.
- measure
- Overall Survival (OS)
- time Frame
- From randomisation up to 374 weeks
- 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.
- measure
- Time to Objective Response (OR)
- 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
- 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.
- measure
- Duration of Objective Response
- 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
- 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.
- measure
- Duration of Disease Control
- 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
- 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.
- measure
- Tumour Shrinkage
- 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
- description
- The change from baseline to the lowest and the last body weight recorded or during the the study.
- measure
- Change From Baseline in Body Weight
- time Frame
- Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
- 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; 1. Restricted in physically strenuous activity, but ambulatory and able to carry out light or sedentary work; 2. Ambulatory (\>50 percent of waking hours), capable of all selfcare, unable to carry out any work activities; 3. Capable of only limited self care, confined to bed or chair more then 50 percent of waking hours; 4. Completely disabled, cannot carry on any selfcare, totally confined to bed or chair; 5. Dead
- measure
- Change From Baseline in Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
- time Frame
- Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
- 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.
- measure
- Health Related Quality of Life (HRQOL): Time of Deterioration in Coughing
- time Frame
- Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
- 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.
- measure
- Health Related Quality of Life (HRQOL): Time of Deterioration in Dyspnoea
- time Frame
- Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
- 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.
- measure
- Health Related Quality of Life (HRQOL): Time of Deterioration in Pain
- time Frame
- Baseline and throughout the study (every 3 weeks) until progression or death (whichever occurs first) up to 374 weeks.
Full 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
Source references
- references
- 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.
- pmid
- 30584317
- type
- DERIVED
- 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.
- pmid
- 29653820
- type
- DERIVED
- 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.
- pmid
- 27601237
- type
- DERIVED
- 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.
- pmid
- 26823294
- type
- DERIVED
- 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.
- pmid
- 26051236
- type
- DERIVED
- 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.
- pmid
- 25589191
- type
- DERIVED
- 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.
- pmid
- 24439929
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice