BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation

NCT ID: NCT00949650

Last Updated: 2018-04-06

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

345 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-08-14

Study Completion Date

2017-03-16

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Carcinoma, Non-Small-Cell Lung Adenocarcinoma

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

BIBW 2992

BIBW 2992 tablet once daily until progression

Group Type EXPERIMENTAL

BIBW 2992

Intervention Type DRUG

BIBW 2992 once daily until progression

Cisplatin/Pemetrexed

Cisplatin and Pemetrexed IV once every 3 weeks for up to 6 cycles

Group Type ACTIVE_COMPARATOR

Pemetrexed

Intervention Type DRUG

Pemetrexed IV given once every 3 weeks for up to 6 cycles

Cisplatin

Intervention Type DRUG

Cisplatin IV given once every 3 weeks for up to 6 cycles

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Pemetrexed

Pemetrexed IV given once every 3 weeks for up to 6 cycles

Intervention Type DRUG

BIBW 2992

BIBW 2992 once daily until progression

Intervention Type DRUG

Cisplatin

Cisplatin IV given once every 3 weeks for up to 6 cycles

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Boehringer Ingelheim

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Medical Radiology Science Centre

Obninsk, , Russia

Site Status

First Pavlov State Medical University Saint Petersburg

Saint Petersburg, , Russia

Site Status

Highlands Oncology Group

Fayetteville, Arkansas, United States

Site Status

Clinical Trials and Research Associates Inc

Montebello, California, United States

Site Status

Innovative Medical Research of South Florida

Miami, Florida, United States

Site Status

Crescent City Research Consortiom

Marrero, Louisiana, United States

Site Status

Interlakes Foundation, Incorporated

Rochester, New York, United States

Site Status

Lehigh Valley Hospital / Lehigh Valley Health Network

Allentown, Pennsylvania, United States

Site Status

South Texas Institute of Cancer, Northwest Cancer Center

Corpus Christi, Texas, United States

Site Status

Instituto de Medicina Nuclear de Bahía Blanca

Bahía Blanca, , Argentina

Site Status

Hospital Alemán

Capital Federal, , Argentina

Site Status

Imcaba S.R.L.

Capital Federal, , Argentina

Site Status

IMAI Research

Capital Federal, , Argentina

Site Status

Instituto Alexander Fleming

Capital Federal, , Argentina

Site Status

Hospital Militar Central

Capital Federal, , Argentina

Site Status

PALIAR

Capital Federal, , Argentina

Site Status

Centro Oncológico de Rosario

Rosario, , Argentina

Site Status

Lifehouse

Camperdown, New South Wales, Australia

Site Status

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Site Status

Calvary Mater Newcastle Hospital

Waratah, New South Wales, Australia

Site Status

The Prince Charles Hospital

Chermside, Queensland, Australia

Site Status

Flinders Medical Centre

Bedford Park, South Australia, Australia

Site Status

The Burnside War Memorial Hospital

Toorak Gardens, South Australia, Australia

Site Status

Box Hill Hospital

Box Hill, Victoria, Australia

Site Status

St. Vincents Hospital (MEL)

Fitzroy, Victoria, Australia

Site Status

Mount Medical Centre

Perth, Western Australia, Australia

Site Status

KH d. Elisabethinen Linz

Linz, , Austria

Site Status

SMZ Baumgartner Hoehe Otto Wagner Spital

Vienna, , Austria

Site Status

Klinikum Wels - Grieskirchen GmbH

Wels, , Austria

Site Status

Brussels - UNIV St-Pierre

Brussels, , Belgium

Site Status

UNIV UZ Gent

Ghent, , Belgium

Site Status

Brussels - UNIV UZ Brussel

Jette, , Belgium

Site Status

UZ Leuven

Leuven, , Belgium

Site Status

Centre Hospitalier Universitaire de Liège

Liège, , Belgium

Site Status

Centro de Pesquisa do Hospital Lifecenter

Belo Horizonte, , Brazil

Site Status

Centro de Pesquisas Clínicas em Oncología

Cachoeiro de Itapemirim, , Brazil

Site Status

Insituto de Oncologia do Paraná

Curitiba, , Brazil

Site Status

Hospital São Lucas da Pontifícia Universidade Católica

Porto Alegre, , Brazil

Site Status

UNIFESP Departamento de Medicina de Pneumologia

São Paulo, , Brazil

Site Status

Tom Baker Cancer Centre

Calgary, Alberta, Canada

Site Status

Cross Cancer Institute (University of Alberta)

Edmonton, Alberta, Canada

Site Status

Charles LeMoyne Hospital

Greenfield Park, Migration Data, Canada

Site Status

Hematologiste et oncologue medical CHUM - Hopital Notre-Dame

Montreal, Migration Data, Canada

Site Status

McGill University, Department of Oncology

Montreal, Migration Data, Canada

Site Status

Hospital Dirección de Previsión de Carabineros

Los Condes, , Chile

Site Status

Instituto Oncológico Limitada Viña del Mar

Reñaca, , Chile

Site Status

Instituto Clínico Oncológico del Sur - ICOS

Temuco, , Chile

Site Status

HOP d'Angers

Angers, , France

Site Status

HOP Côte de Nacre

Caen, , France

Site Status

HOP Nord Michallon

La Tronche, , France

Site Status

HOP Croix Rousse, Pneumo, Lyon

Lyon, , France

Site Status

INS Curie

Paris, , France

Site Status

HOP Sud-Réunion, Pneumo, Saint Pierre

Saint Pierre - La Réunion, , France

Site Status

CTR René Gauducheau

Saint-Herblain, , France

Site Status

HOP - HIA Sainte Anne

Toulon, , France

Site Status

HOP, Pneumo, Villefranche sur Saône

Villefranche-sur-Saône, , France

Site Status

Universitätsklinikum Benjamin Franklin, Berlin

Berlin, , Germany

Site Status

Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH

Essen, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Lungenklinik Hemer

Hemer, , Germany

Site Status

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, , Germany

Site Status

Universitätsklinikum Münster

Münster, , Germany

Site Status

Pius-Hospital, Oldenburg

Oldenburg, , Germany

Site Status

National Taiwan University Hospital

Taipei, , Germany

Site Status

Queen Mary Hospital

Hong Kong, , Hong Kong

Site Status

Prince of Wales Hospital

Shatin, , Hong Kong

Site Status

Szent György Hospital, Szekesfehervar

Székesfehérvár, , Hungary

Site Status

Markusovszky County Hospital, Szombathely

Szombathely, , Hungary

Site Status

Zala County Hospital, Zalaegerszeg

Zalaegerszeg, , Hungary

Site Status

St James's Hospital

Dublin, , Ireland

Site Status

Ospedale San Donato di Arezzo

Arezzo, , Italy

Site Status

Az. USL 4 di Prato

Prato, , Italy

Site Status

Azienda Ospedaliera Sant'Andrea-Università di Roma La Sapienza

Roma, , Italy

Site Status

Osp. Silvestrin

Sant'Andrea Delle Fratte (PG), , Italy

Site Status

National Hospital Organization Nagoya Medical Center

Aichi, Nagoya, , Japan

Site Status

Aichi Cancer Center Hospital

Aichi, Nagoya, , Japan

Site Status

National Cancer Center Hospital East

Chiba, Kashiwa, , Japan

Site Status

National Hospital Organization Shikoku Cancer Center

Ehime, Matsuyama, , Japan

Site Status

National Hospital Organization Kyushu Cancer Center

Fukuoka, Fukuoka, , Japan

Site Status

Hokkaido University Hospital

Hokkaido, Sapporo, , Japan

Site Status

Institute of Biomedical Research and Innovation Hospital

Hyogo, Kobe, , Japan

Site Status

Kanazawa University Hospital

Ishikawa, Kanazawa, , Japan

Site Status

Kanagawa Cardiovascular and Respiratory Center

Kanagawa, Yokohama, , Japan

Site Status

Niigata Cancer Center Hospital

Niigata, Niigata, , Japan

Site Status

Kurashiki Central Hospital

Okayama, Kurashiki, , Japan

Site Status

Okayama University Hospital

Okayama, Okayama, , Japan

Site Status

Kindai University Hospital

Osaka, Osaka-Sayama, , Japan

Site Status

Osaka City Hospital Organization Osaka City General Hospital

Osaka, Osaka, , Japan

Site Status

National Hospital Organization Kinki-Chuo Chest Medical Center

Sakai, Osaka, , Japan

Site Status

Shizuoka Cancer Center

Shizuoka, Sunto-gun, , Japan

Site Status

Hospital Pulau Pinang

Palau Pinang, , Malaysia

Site Status

Pusat Perubatan University Kebangsaan Malaysia

Wilayah Persekutuan, , Malaysia

Site Status

University Malaya Medical Centre

Wilayah Persekutuan, , Malaysia

Site Status

Hospital Nacional Guillermo Almenara Irigoyen

La Victoria, , Peru

Site Status

Clínica Anglo Americana

San Isidro, , Peru

Site Status

Instituto Nacional de Enfermedades Neoplásicas

Surquillo, , Peru

Site Status

Perpetual Succour Hospital (Cebu)

Cebu City, , Philippines

Site Status

Makati Medical Center

Makati City, , Philippines

Site Status

St. Luke Medical Centre

Quezon, , Philippines

Site Status

Institutul Oncologic "Prof. Dr. Ion Chiricuta"

Cluj-Napoca, , Romania

Site Status

ONCOLAB SRL, Craiova

Craiova, , Romania

Site Status

Republic Clinical Oncology Dispensary, Dept. Chemotherapy

Kazan', , Russia

Site Status

FSBSI "N.N Blokhin Medical Research Center of Oncology"

Moscow, , Russia

Site Status

SPb SBIH "City Clinical Oncological Dispensary"

Saint Petersburg, , Russia

Site Status

FSBI "N.N. Petrov National Medical Research Center of Oncology" of MoH of RF

Saint Petersburg, , Russia

Site Status

Chungbuk National University Hospital

Cheongju-si, , South Korea

Site Status

Chonnam National University Hwasun Hospital

Hwasun, , South Korea

Site Status

Seoul National University Bundang Hospital

Seongnam, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Ulsan University Hospital

Ulsan, , South Korea

Site Status

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status

Chang Gung Memorial Hospital Kaohsiung

Kaohsiung City, , Taiwan

Site Status

China Medical University Hospital

Taichung, , Taiwan

Site Status

Taichung Veterans General Hospital

Taichung, , Taiwan

Site Status

NCKUH

Tainan City, , Taiwan

Site Status

Taipe Veterans General Hospital

Taipei, , Taiwan

Site Status

Tri-Service General Hospital

Taipei, , Taiwan

Site Status

Chang Gung Memorial Hospital(TaoYuan)

Taoyuan District, , Taiwan

Site Status

Ramathibodi Hospital

Bangkok, , Thailand

Site Status

Maharaj Nakorn Chiang Mai Hospital

Chiang Mai, , Thailand

Site Status

Srinagarind Hospital

Khonkaen, , Thailand

Site Status

Songklanagarind Hospital

Songkhla, , Thailand

Site Status

City Clinical Hospital #4, Dnipropetrovsk State Medical Academy

Dnipropetrovsk, , Ukraine

Site Status

Donetsk Regional Antitumor Centre

Donetsk, , Ukraine

Site Status

Kharkiv Regional Clinical Oncology Center

Kharkiv, , Ukraine

Site Status

Lviv State Oncological Regional Treatment & Diagnostic CTR

Lviv, , Ukraine

Site Status

Royal Devon and Exeter Hospital

Exeter, , United Kingdom

Site Status

Royal Surrey County Hospital

Guildford, , United Kingdom

Site Status

The Royal Marsden Hospital

London, , United Kingdom

Site Status

Maidstone Hospital, Kent Oncology Centre

Maidstone, , United Kingdom

Site Status

Scunthorpe General Hospital, Oncology

Scunthorpe, , United Kingdom

Site Status

The Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Royal Cornwall Hospital

Truro, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Argentina Australia Austria Belgium Brazil Canada Chile France Germany Hong Kong Hungary Ireland Italy Japan Malaysia Peru Philippines Romania Russia South Korea Taiwan Thailand Ukraine United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type DERIVED
PMID: 37235976 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29653820 (View on PubMed)

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.

Reference Type DERIVED
PMID: 27601237 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26823294 (View on PubMed)

Kato 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.

Reference Type DERIVED
PMID: 26094656 (View on PubMed)

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.

Reference Type DERIVED
PMID: 26051236 (View on PubMed)

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.

Reference Type DERIVED
PMID: 25589191 (View on PubMed)

Yang 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.

Reference Type DERIVED
PMID: 23816967 (View on PubMed)

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. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.

Reference Type DERIVED
PMID: 23816960 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2008-005615-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1200.32

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Afatinib Expanded Access Program
NCT01649284 APPROVED_FOR_MARKETING
Afatinib With CT and RT for EGFR-Mutant NSCLC
NCT01553942 ACTIVE_NOT_RECRUITING PHASE2