Carcinoma, Non-Small-Cell LungPhase 3NCT00949650
BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation
A Phase 3 study testing Pemetrexed, BIBW 2992 and Cisplatin in people with Carcinoma, Non-Small-Cell Lung and Adenocarcinoma, run by Boehringer Ingelheim at 133 sites in 25 countries.
Trial summary
This randomised, open label phase III trial will be performed in patients with adenocarcinoma of the lung with tumours harbouring an Epidermal Growth Factor Receptor activating mutation. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung, Adenocarcinoma
- What is being tested?
- Pemetrexed, BIBW 2992 and Cisplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 345 participants
- Where
- 133 sitesin 25 countries
- Study dates
- 14 Aug 2009to 16 Mar 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed diagnosis of Stage IIIB (with cytologically proven pleural effusion or pericardial effusion) or Stage IV adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
- Epidermal Growth Factor Receptor mutation detected by central laboratory analysis of tumour biopsy material.
- Measurable disease according to RECIST 1.1.
- Eastern Cooperative Oncology Group 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 guidelines.
Who cannot join
- Prior chemotherapy for relapsed and/or metastatic NSCLC. Neoadjuvant/adjuvant chemotherapy is permitted if at least 12 months has elapsed between the end of chemotherapy and randomisation.
- Prior treatment with Epidermal Growth Factor Receptor targeting small molecules or antibodies.
- Radiotherapy or surgery (other than biopsy) within 4 weeks prior to randomisation.
- Active brain metastases
- Any other current malignancy or malignancy diagnosed within the past five years
- Known pre-existing interstitial lung disease.
Show all 12Show fewer
- Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom.
- History or presence of clinically relevant cardiovascular abnormalities.
- Any other concomitant serious illness or organ system dysfunction.
- Adequate absolute neutrophil count and platelet count
- Adequate liver and kidney function
- Active hepatitis B infection, active hepatitis C infection or known HIV carrier.
Trial locations and contacts
133 sites in 25 countries.
133 sites in 25 countries
Japan16 sites
National Hospital Organization Nagoya Medical Center
Aichi, Nagoya, 460-0001
Aichi Cancer Center Hospital
Aichi, Nagoya, 464-8681
National Cancer Center Hospital East
Chiba, Kashiwa, 277-8577
National Hospital Organization Shikoku Cancer Center
Ehime, Matsuyama, 791-0280
National Hospital Organization Kyushu Cancer Center
Fukuoka, Fukuoka, 811-1395
Hokkaido University Hospital
Hokkaido, Sapporo, 060-8648
Institute of Biomedical Research and Innovation Hospital
Hyogo, Kobe, 650-0047
Kanazawa University Hospital
Ishikawa, Kanazawa, 920-8641
Kanagawa Cardiovascular and Respiratory Center
Kanagawa, Yokohama, 236-0051
Niigata Cancer Center Hospital
Niigata, Niigata, 951-8566
Kurashiki Central Hospital
Okayama, Kurashiki, 710-8602
Okayama University Hospital
Okayama, Okayama, 700-8558
Osaka City Hospital Organization Osaka City General Hospital
Osaka, Osaka, 534-0021
Kindai University Hospital
Osaka, Osaka-Sayama, 589-8511
National Hospital Organization Kinki-Chuo Chest Medical Center
Sakai, Osaka, 591-8555
Shizuoka Cancer Center
Shizuoka, Sunto-gun, 411-8777
Australia9 sites
Flinders Medical Centre
Bedford Park, South Australia, 5042
Box Hill Hospital
Box Hill, Victoria, 3128
Lifehouse
Camperdown, New South Wales, 2050
The Prince Charles Hospital
Chermside, Queensland, 4032
St. Vincents Hospital (MEL)
Fitzroy, Victoria, 3065
Mount Medical Centre
Perth, Western Australia, 6000
Royal North Shore Hospital
St Leonards, New South Wales, 2065
The Burnside War Memorial Hospital
Toorak Gardens, South Australia, 5065
Calvary Mater Newcastle Hospital
Waratah, New South Wales, 2298
France9 sites
HOP d'Angers
Angers, 49933
HOP Côte de Nacre
Caen, 14033
HOP Nord Michallon
La Tronche, 38700
HOP Croix Rousse, Pneumo, Lyon
Lyon, 69317
INS Curie
Paris, 75248
HOP Sud-Réunion, Pneumo, Saint Pierre
Saint Pierre - La Réunion, 97448
CTR René Gauducheau
Saint-Herblain, 44805
HOP - HIA Sainte Anne
Toulon, 83041
HOP, Pneumo, Villefranche sur Saône
Villefranche-sur-Saône, 69655
Argentina8 sites
Instituto de Medicina Nuclear de Bahía Blanca
Bahía Blanca, B8000FJI
Hospital Alemán
Capital Federal, C1118AAT
Imcaba S.R.L.
Capital Federal, C1185AAT
IMAI Research
Capital Federal, C1425AWC
Instituto Alexander Fleming
Capital Federal, C1426ANZ
Hospital Militar Central
Capital Federal, C1426BOR
PALIAR
Capital Federal, C1430ERF
Centro Oncológico de Rosario
Rosario, S2000KZE
Germany8 sites
Universitätsklinikum Benjamin Franklin, Berlin
Berlin, 12200
Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
Essen, 45122
Medizinische Hochschule Hannover
Hanover, 30625
Lungenklinik Hemer
Hemer, 58675
Universitätsmedizin der Johannes Gutenberg-Universität Mainz
Mainz, 55101
Universitätsklinikum Münster
Münster, 48149
Pius-Hospital, Oldenburg
Oldenburg, 26121
National Taiwan University Hospital
Taipei, 100
Taiwan8 sites
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807
Chang Gung Memorial Hospital Kaohsiung
Kaohsiung City, 833
China Medical University Hospital
Taichung, 40447
Taichung Veterans General Hospital
Taichung, 40705
NCKUH
Tainan, 704
Taipe Veterans General Hospital
Taipei, 112
Tri-Service General Hospital
Taipei, 114
Chang Gung Memorial Hospital(TaoYuan)
Taoyuan, 33305
United States7 sites
Lehigh Valley Hospital / Lehigh Valley Health Network
Allentown, Pennsylvania, 18103
South Texas Institute of Cancer, Northwest Cancer Center
Corpus Christi, Texas, 78410
Highlands Oncology Group
Fayetteville, Arkansas, 72703
Crescent City Research Consortiom
Marrero, Louisiana, 70072
Innovative Medical Research of South Florida
Miami, Florida, 33179
Clinical Trials and Research Associates Inc
Montebello, California, 90640
Interlakes Foundation, Incorporated
Rochester, New York, 14623
United Kingdom7 sites
Royal Devon and Exeter Hospital
Exeter, EX2 5DW
Royal Surrey County Hospital
Guildford, GU2 7XX
The Royal Marsden Hospital
London, SW3 6JJ
Maidstone Hospital, Kent Oncology Centre
Maidstone, ME16 9QQ
Scunthorpe General Hospital, Oncology
Scunthorpe, DN15 7BH
The Royal Marsden Hospital
Sutton, SM2 5PT
Royal Cornwall Hospital
Truro, TR1 3LJ
Russia6 sites
Republic Clinical Oncology Dispensary, Dept. Chemotherapy
Kazan', 420029
FSBSI "N.N Blokhin Medical Research Center of Oncology"
Moscow, 115478
Medical Radiology Science Centre
Obninsk, 249020
First Pavlov State Medical University Saint Petersburg
Saint Petersburg, 197022
SPb SBIH "City Clinical Oncological Dispensary"
Saint Petersburg, 197022
FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF
Saint Petersburg, 197758
Belgium5 sites
Brussels - UNIV St-Pierre
Brussels, 1000
UNIV UZ Gent
Ghent, 9000
Brussels - UNIV UZ Brussel
Jette, 1090
UZ Leuven
Leuven, 3000
Centre Hospitalier Universitaire de Liège
Liège, 4000
Brazil5 sites
Centro de Pesquisa do Hospital Lifecenter
Belo Horizonte
Centro de Pesquisas Clínicas em Oncología
Cachoeiro de Itapemirim, 29308-014
Insituto de Oncologia do Paraná
Curitiba, 80530-010
Hospital São Lucas da Pontifícia Universidade Católica
Porto Alegre, 90610-000
UNIFESP Departamento de Medicina de Pneumologia
São Paulo, 04023-900
Canada5 sites
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2
Cross Cancer Institute (University of Alberta)
Edmonton, Alberta, T6G 1Z2
Charles LeMoyne Hospital
Greenfield Park, Migration Data, J4V 2H1
Hematologiste et oncologue medical CHUM - Hopital Notre-Dame
Montreal, Migration Data, H2L 4M1
McGill University, Department of Oncology
Montreal, Migration Data, H2W 1S6
South Korea5 sites
Chungbuk National University Hospital
Cheongju-si, 361-771
Chonnam National University Hwasun Hospital
Hwasun, 519-763
Seoul National University Bundang Hospital
Seongnam, 13620
Asan Medical Center
Seoul, 138-736
Ulsan University Hospital
Ulsan, 682-714
Italy4 sites
Ospedale San Donato di Arezzo
Arezzo, 52100
Az. USL 4 di Prato
Prato, 59100
Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza
Roma, 00189
Osp. Silvestrin
Sant'Andrea Delle Fratte (PG), 06132
Thailand4 sites
Ramathibodi Hospital
Bangkok, 10400
Maharaj Nakorn Chiang Mai Hospital
Chiang Mai, 50200
Srinagarind Hospital
Khonkaen, 40002
Songklanagarind Hospital
Songkhla, 90110
Ukraine4 sites
City Clinical Hospital #4, Dnipropetrovsk State Medical Academy
Dnipropetrovsk, 49102
Donetsk Regional Antitumor Centre
Donetsk, 83000
Kharkiv Regional Clinical Oncology Center
Kharkiv, 16070
Lviv State Oncological Regional Treatment & Diagnostic CTR
Lviv, 79031
Austria3 sites
KH d. Elisabethinen Linz
Linz, 4010
SMZ Baumgartner Hoehe Otto Wagner Spital
Vienna, 1140
Klinikum Wels - Grieskirchen GmbH
Wels, 4600
Chile3 sites
Hospital Dirección de Previsión de Carabineros
Los Condes, 760-0746
Instituto Oncológico Limitada Viña del Mar
Reñaca, 2540364
Instituto Clínico Oncológico del Sur - ICOS
Temuco
Hungary3 sites
Szent György Hospital, Szekesfehervar
Székesfehérvár, 8000
Markusovszky County Hospital, Szombathely
Szombathely, 9700
Zala County Hospital, Zalaegerszeg
Zalaegerszeg, 8900
Malaysia3 sites
Hospital Pulau Pinang
Palau Pinang, 10990
Pusat Perubatan University Kebangsaan Malaysia
Wilayah Persekutuan, 5600
University Malaya Medical Centre
Wilayah Persekutuan, 59100
Peru3 sites
Hospital Nacional Guillermo Almenara Irigoyen
La Victoria
Clínica Anglo Americana
San Isidro, 27
Instituto Nacional de Enfermedades Neoplásicas
Surquillo, 34
Philippines3 sites
Perpetual Succour Hospital (Cebu)
Cebu City, 6000
Makati Medical Center
Makati City, 1229
St. Luke Medical Centre
Quezon, 1102
Hong Kong2 sites
Queen Mary Hospital
Hong Kong
Prince of Wales Hospital
Shatin
Romania2 sites
Institutul Oncologic "Prof. Dr. Ion Chiricuta"
Cluj-Napoca, 400015
ONCOLAB SRL, Craiova
Craiova, 200535
About this study
Official title: A Randomised, 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
This randomised, open label phase III trial will be performed in patients with adenocarcinoma of the lung with tumours harbouring an Epidermal Growth Factor Receptor activating mutation. The objectives of the trial are to compare the efficacy of single agent BIBW 2992, Arm A, with Pemetrexed/Cisplatin chemotherapy, Arm B, as first line treatment for this group of patients.
- Conditions
- Carcinoma, Non-Small-Cell Lung, Adenocarcinoma
- Being tested
- Pemetrexed, BIBW 2992, Cisplatin
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Adenocarcinoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PemetrexedDrug
Pemetrexed IV given once every 3 weeks for up to 6 cycles
BIBW 2992Drug
BIBW 2992 once daily until progression
CisplatinDrug
Cisplatin IV given once every 3 weeks for up to 6 cycles
| Study group | Role | What they receive |
|---|---|---|
| BIBW 2992 | Experimental | BIBW 2992 tablet once daily until progression Receives: Drug: BIBW 2992 |
| Cisplatin/Pemetrexed | Active comparator | Cisplatin and Pemetrexed IV once every 3 weeks for up to 6 cycles Receives: Drug: Pemetrexed; Drug: Cisplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-Free Survival (PFS) Time
PFS was defined as time from randomisation to disease progression or death whichever occured first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.
Measured: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Secondary outcomes (12)
Percentage of Patients With Objective Response (OR)
OR was defined as Complete Response (CR) or Partial Response (PR). Assessed by central independent review according to RECIST 1.1.
Measured: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Percentage of Participants With Disease Control (DC)
DC was defined as a patient with OR or Stable Disease (SD). Assessed by central independent review according to the RECIST 1.1.
Measured: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Overall Survival (OS) Time
OS was defined as time from randomisation to death.
Measured: From randomisation to cut-off date (17MAR2017).
Tumour Shrinkage
Tumour shrinkage was calculated as the minimum Sum of Diameters (SoD) of target lesions from all post-baseline tumour assessments, as read by the central independent review. The mean of these minimum values were presented after adjusting for baseline SoD, EGFR mutation group and race.
Measured: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Change From Baseline in Body Weight
Because the PFS was longer for patients in the Afatinib arm than for patients in the chemotherapy arm, the period of data collection for ECOG status and body weight continued for a longer time in the Afatinib arm.
Measured: Baseline and throughout the trial until progression (every 3 weeks), up to 28 months.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
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 self-care, unable to carry out any work activities.
- Capable of only limited self-care, confined to bed or chair more than 50 percent of waking hours.
- Completely disabled, cannot carry on any self-care, totally confined to bed or chair.
- Dead.
Measured: Throughout the trial until progression (every 3 weeks), up to 28 months.
Health Related Quality of Life (HRQOL): Time to Deterioration in Coughing
HRQOL was measured by European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire C30 (QLQ-C30) and its lung cancer specific module LC13 (QLQ-LC13). Analysis for cough is based on QLQ-LC13 question 1. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.
Measured: Throughout the trial until progression (every 3 weeks).
HRQOL: Time to Deterioration in Dyspnoea
HRQOL was measured by EORTC QLQ-C30 and its lung cancer specific module QLQ-LC13. Analysis for dyspnoea is based on composite of QLQ-LC13 questions 3-5. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.
Measured: Throughout the trial until progression (every 3 weeks).
HRQOL: Time to Deterioration in Pain
HRQOL was measured by EORTC QLQ-C30 and its lung cancer specific module QLQ-LC13. Analysis for pain is based on composite of QLQ-C30 questions 9 and 19. Time to deterioration was defined as the time from randomisation to a score increased (worsened) by at least 10 points from baseline (0-100 point scale). Patients were considered deteriorated at time of death. Median time results from unstratified Kaplan-Meier estimates.
Measured: Throughout the trial until progression (every 3 weeks).
Trough Plasma Concentrations of Afatinib at Day 22
Trough plasma concentrations of Afatinib at Day 22 (course 2, visit 1) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.
Measured: Day 22.
Trough Plasma Concentrations of Afatinib at Day 29
Trough plasma concentrations of Afatinib at day 29 (course 2, visit 2) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.
Measured: Day 29.
Trough Plasma Concentrations of Afatinib at Day 43
Trough plasma concentrations of Afatinib at Day 43 (course 3, visit 1) after multiple daily dosing of 40 mg Afatinib and after dose escalation to 50 mg or dose reduction to 30 mg or 20 mg.
Measured: Day 43.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2009 (estimated)
- Study start14 Aug 2009
- Primary completion9 Feb 2012
- Study completion16 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 345 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00949650
- Sponsor's protocol ID
- 1200.32
- Other IDs
- 2008-005615-18, 2008
- Status last verified
- Mar 2018
- First submitted
- 29 Jul 2009
- Last updated
- 6 Apr 2018
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2023 Jun 1;41(16):2869-2876. doi: 10.1200/JCO.22.02547.
PubMed 37235976Wu 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.
PubMed 29653820Yang 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.
PubMed 27601237Schuler 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.
PubMed 26823294Kato T, Yoshioka H, Okamoto I, Yokoyama A, Hida T, Seto T, Kiura K, Massey D, Seki Y, Yamamoto N. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX-Lung 3. Cancer Sci. 2015 Sep;106(9):1202-11. doi: 10.1111/cas.12723. Epub 2015 Jul 25.
PubMed 26094656Yang 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.
PubMed 26051236Yang 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.
PubMed 25589191Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. doi: 10.1200/JCO.2012.46.1764. Epub 2013 Jul 1.
PubMed 23816967Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.
PubMed 23816960
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised, 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
- ClinicalTrials.gov ID
- NCT00949650
- Acronym / sponsor ID
- 1200.32
- Conditions
- Carcinoma, Non-Small-Cell Lung, Adenocarcinoma
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 345 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 14 Aug 2009 (actual)
- Primary completion
- 9 Feb 2012 (actual)
- Study completion
- 16 Mar 2017 (actual)
- First posted
- 30 Jul 2009 (estimated)
- Results
- Posted 19 Nov 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomised, open label phase III trial will be performed in patients with adenocarcinoma of the lung with tumours harbouring an Epidermal Growth Factor Receptor activating mutation. The objectives of the trial are to compare the efficacy of single agent BIBW 2992, Arm A, with Pemetrexed/Cisplatin chemotherapy, Arm B, as first line treatment for this group of patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| BIBW 2992 | Experimental | Drug: BIBW 2992BIBW 2992 tablet once daily until progression |
| Cisplatin/Pemetrexed | Active comparator | Drug: Pemetrexed, Drug: CisplatinCisplatin and Pemetrexed IV once every 3 weeks for up to 6 cycles |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Pathologically confirmed diagnosis of Stage IIIB (with cytologically proven pleural effusion or pericardial effusion) or Stage IV adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
- Epidermal Growth Factor Receptor mutation detected by central laboratory analysis of tumour biopsy material.
- Measurable disease according to RECIST 1.1.
- Eastern Cooperative Oncology Group score of 0 or 1.
- Age >/= 18 years.
Key exclusion criteria (12 listed)
- Prior chemotherapy for relapsed and/or metastatic NSCLC. Neoadjuvant/adjuvant chemotherapy is permitted if at least 12 months has elapsed between the end of chemotherapy and randomisation.
- Prior treatment with Epidermal Growth Factor Receptor targeting small molecules or antibodies.
- Radiotherapy or surgery (other than biopsy) within 4 weeks prior to randomisation.
- Active brain metastases
- Any other current malignancy or malignancy diagnosed within the past five years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PemetrexedPemetrexed IV given once every 3 weeks for up to 6 cycles | Drug | Cisplatin/Pemetrexed |
| BIBW 2992BIBW 2992 once daily until progression | Drug | BIBW 2992 |
| CisplatinCisplatin IV given once every 3 weeks for up to 6 cycles | Drug | Cisplatin/Pemetrexed |
Primary outcome
Progression-Free Survival (PFS) Time
Time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
PFS was defined as time from randomisation to disease progression or death whichever occured first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1). Median time results from unstratified Kaplan-Meier estimates.
12 secondary outcomes
Percentage of Patients With Objective Response (OR)
Time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Percentage of Participants With Disease Control (DC)
Time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Overall Survival (OS) Time
Time frame: From randomisation to cut-off date (17MAR2017).
Tumour Shrinkage
Time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Change From Baseline in Body Weight
Time frame: Baseline and throughout the trial until progression (every 3 weeks), up to 28 months.
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Time frame: Throughout the trial until progression (every 3 weeks), up to 28 months.
Health Related Quality of Life (HRQOL): Time to Deterioration in Coughing
Time frame: Throughout the trial until progression (every 3 weeks).
HRQOL: Time to Deterioration in Dyspnoea
Time frame: Throughout the trial until progression (every 3 weeks).
HRQOL: Time to Deterioration in Pain
Time frame: Throughout the trial until progression (every 3 weeks).
Trough Plasma Concentrations of Afatinib at Day 22
Time frame: Day 22.
Trough Plasma Concentrations of Afatinib at Day 29
Time frame: Day 29.
Trough Plasma Concentrations of Afatinib at Day 43
Time frame: Day 43.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Apr 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 37235976Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III Study of Afatinib or Cisplatin Plus Pemetrexed in Patients With Metastatic Lung Adenocarcinoma With EGFR Mutations. J Clin Oncol. 2023 Jun 1;41(16):2869-2876. doi: 10.1200/JCO.22.02547.
- Derived from this study: PubMed 29653820Wu 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.
- Derived from this study: PubMed 27601237Yang 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.
- Derived from this study: PubMed 26823294Schuler 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.
- Derived from this study: PubMed 26094656Kato T, Yoshioka H, Okamoto I, Yokoyama A, Hida T, Seto T, Kiura K, Massey D, Seki Y, Yamamoto N. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX-Lung 3. Cancer Sci. 2015 Sep;106(9):1202-11. doi: 10.1111/cas.12723. Epub 2015 Jul 25.
- Derived from this study: PubMed 26051236Yang 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.
- Derived from this study: PubMed 25589191Yang 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.
- Derived from this study: PubMed 23816967Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. doi: 10.1200/JCO.2012.46.1764. Epub 2013 Jul 1.
- Derived from this study: PubMed 23816960Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boehringer Ingelheim study chair
Boehringer Ingelheim
133 sites in 25 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pemetrexed, BIBW 2992 and Cisplatin in people with Carcinoma, Non-Small-Cell Lung and Adenocarcinoma, run by Boehringer Ingelheim at 133 sites in 25 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 133 sites in Japan, Australia, France, Argentina, Germany and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-Free Survival (PFS) Time (time frame: Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00949650, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2018.