LUX-Lung 8: A Phase III Trial of Afatinib (BIBW 2992) Versus Erlotinib for the Treatment of Squamous Cell Lung Cancer After at Least One Prior Platinum Based Chemotherapy

NCT ID: NCT01523587

Last Updated: 2019-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 795 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-05
• Study Completion Date: 2017-12-27

Brief Summary

This randomised, open-label phase III trial will be performed in patients with advanced squamous cell carcinoma of the lung requiring second-line treatment after receiving first-line platinum-based chemotherapy. The primary objective of this trial is to compare the efficacy of BIBW 2992 to erlotinib as second-line treatment in this group of patients.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Afatinib

Patients receive afatinib tablets once daily

Group Type: EXPERIMENTAL

afatinib

Intervention Type: DRUG

Afatinib taken once daily, continuously until disease progression or unacceptable toxicity.

Erlotinib

Patients receive erlotinib tablets once daily

Group Type: ACTIVE_COMPARATOR

erlotinib

Intervention Type: DRUG

erlotinib taken once daily

Interventions

afatinib

Afatinib taken once daily, continuously until disease progression or unacceptable toxicity.

Intervention Type: DRUG

erlotinib

erlotinib taken once daily

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Diagnosis of advanced stage NSCLC squamous histology.

2. Platinum-based doublet chemotherapy as 1st line treatment of Stage IIIB/IV NSCLC.

3. Eligible to receive 2nd line therapy in the opinion of the investigator.

4. Measurable disease according to RECIST 1.1.

5. Adequate Performance Status.

6. Availability of tumour tissue material for correlative studies. Archived tumour tissue is acceptable.

7. Adequate organ function.

8. Age = 18 years and above.

9. Written informed consent that is consistent with International Conference on Harmonisation (ICH)-Good Clinical Practice (GCP) guidelines.

Exclusion Criteria

1. Prior treatment with Epidermal Growth Factor Receptor (EGFR) directed small molecules or antibodies.

2. Radiotherapy within 4 weeks prior to randomization.

3. Active brain metastases .

4. Any other current malignancy or malignancy diagnosed within the past three (3) years (other than basal-cell carcinoma of the skin, in situ cervical cancer, in situ prostate cancer).

5. Known pre-existing interstitial lung disease.

6. Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom

7. 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.

8. Women of child-bearing potential and men who are able to father a child, unwilling to be abstinent or use adequate contraception prior to study entry, for the duration of study participation and for at least 2 months after treatment has ended.

9. Female patients of childbearing potential (see Section 4.2.3.3) who:

1. are nursing or

2. are pregnant or

3. are not using an acceptable method of birth control, or do not plan to continue using this method throughout the study and/or do not agree to submit to pregnancy testing required by this protocol.

10. Active hepatitis B infection (defined as presence of Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known HIV carrier.

11. Known or suspected active drug or alcohol abuse in the opinion of the investigator.

12. Any contraindications for therapy with afatinib or erlotinib.

13. Known hypersensitivity to erlotinib, afatinib or the excipients of any of the trial drugs.

14. Major surgery within 4 weeks of starting study treatment.

15. Prior participation in an afatinib clinical study, even if not assigned to afatinib.

16. Use of any investigational drug within 4 weeks of randomisation (unless a longer time period is required by local regulations or by the guidelines for the investigational product).

17. Patients without Progression of their lung cancer.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

Ironwood Cancer and Research Centers

Chandler, Arizona, United States

University of California

La Jolla, California, United States

Sutter Medical Group

Sacramento, California, United States

Boca Raton Reginl Hospital-Lynn Cancer Institute

Boca Raton, Florida, United States

Memorial Healthcare System

Hollywood, Florida, United States

Cancer Care of North Florida, PA

Lake City, Florida, United States

Illinois Cancer Specialists

Niles, Illinois, United States

Orchard Healthcare Research Inc

Skokie, Illinois, United States

University of Louisville

Louisville, Kentucky, United States

West Jefferson General Hospital and Cancer Clinic

Marrero, Louisiana, United States

Lahey Clinic

Burlington, Massachusetts, United States

Commonwealth Hematology-Oncology, PC

Lawrence, Massachusetts, United States

Karmanos Cancer Institute

Detroit, Michigan, United States

Washington University School of Medicine

St Louis, Missouri, United States

Billings Clinic Cancer Center

Billings, Montana, United States

Queens Medical Associates

Fresh Meadows, New York, United States

SUNY Upstate Medical University

Syracuse, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Montefiore Medical Center

The Bronx, New York, United States

Cleveland Clinic

Cleveland, Ohio, United States

The Ohio State University Wexner Medical Center

Columbus, Ohio, United States

Mid Ohio Oncology/Hematology, Inc

Columbus, Ohio, United States

Kaiser Permanente Northwest

Portland, Oregon, United States

Oncology Hematology Associates of Norhtern Pennsylvania, PC

DuBois, Pennsylvania, United States

Kimmel Cancer Center

Philadelphia, Pennsylvania, United States

Temple University Cancer Center

Philadelphia, Pennsylvania, United States

Spartanburg Regional Medical Center

Spartanburg, South Carolina, United States

Cancer Center of Cookeville Regional Medical Center

Cookeville, Tennessee, United States

Paris Cancer Center (PCC), Texas Oncology

Paris, Texas, United States

Cancer Therapy and Research at UTHSCSA

San Antonio, Texas, United States

Fletcher Allen Health Care

Burlington, Vermont, United States

Blue Ridge Cancer Care

Christiansburg, Virginia, United States

Virginia Oncology Associates

Norfolk, Virginia, United States

Instituto Medico Especializado Alexander Fleming

Ciudad Autonoma de Bs As, , Argentina

Instituto Oncologico de Cordoba

Córdoba, , Argentina

Clínica Colombo S.A.

Córdoba, , Argentina

Centro Oncologico de Rosario

Rosario, , Argentina

Centro Oncologico CAIPO

San Miguel de Tucumán, , Argentina

Medical University of Innsbruck

Innsbruck, , Austria

LKH Leoben

Leoben, , Austria

AKH d. Stadt Linz, Pulmologie

Linz, , Austria

SMZ Baumgartner Hoehe Otto Wagner Spital

Vienna, , Austria

BC Cancer Agency - Fraser Valley Centre

Surrey, British Columbia, Canada

Kingston General Hospital

Kingston, Ontario, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

Royal Victoria Hospital

Montreal, Quebec, Canada

Montreal General Hospital - McGill University Health Centre

Montreal, Quebec, Canada

Centro Oncologico Antofagasta

Antofagasta, , Chile

Instituto de Terapias Oncologicas Providencia

Providencia, Santiago, , Chile

Centro Internacional de Estudios Clinicos - CIEC

Recoleta, Santiago de Chile, , Chile

Orlandi Oncologia

Vitacura, , Chile

Beijing Cancer Hospital

Beijing, , China

Beijing Hospital

Beijing, , China

First Hospital of Jilin University

Changchun, , China

Xiangya Hospital, Central South University

Changsha, , China

Sun Yat-Sen University Cancer Center

Guangzhou, , China

the 81th Hospital of PLA

Nanjing, , China

Jiangsu Cancer Hospital

Nanjing, , China

Shanghai Chest Hospital

Shanghai, , China

Shanghai Pulmonary Hospital

Shanghai, , China

Herlev Hospital

Herlev, , Denmark

Næstved Sygehus

Næstved, , Denmark

Odense Universitetshospital

Odense C, , Denmark

HOP d'Angers

Angers, , France

INS Bergonié

Bordeaux, , France

HOP Côte de Nacre

Caen, , France

HOP de Chauny

Chauny, , France

HOP Gabriel-Montpied

Clermont-Ferrand, , France

HOP de Creteil, Pneumo, Creteil

Créteil, , France

HOP Le Mans

Le Mans, , France

CTR Oscar Lambret, Cancéro, Lille

Lille, , France

HOP Calmette

Lille, , France

INS Paoli-Calmettes

Marseille, , France

HOP Nord

Marseille, , France

HOP de Mulhouse, Onco, Mulhouse

Mulhouse, , France

HOP Cochin

Paris, , France

HOP Val de Grâce, Onco, Paris

Paris, , France

INS Jean Godinot, Onco, Reims

Reims, , France

HOP de Rennes, Pneumo, Rennes

Rennes, , France

HOP Saint Quentin, Onco, Saint Quentin

Saint-Quentin, , France

HOP Civil

Strasbourg, , France

HOP Foch

Suresnes, , France

INS Gustave Roussy

Villejuif, , France

Zentralklinik Bad Berka GmbH

Bad Berka, , Germany

Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH

Essen, , Germany

Klinikum Esslingen GmbH

Esslingen am Neckar, , Germany

Universitätsklinikum Frankfurt

Frankfurt am Main, , Germany

Universitätsklinikum Freiburg

Freiburg im Breisgau, , Germany

Universitätsklinikum Hamburg-Eppendorf

Hamburg, , Germany

Lungenklinik Hemer

Hemer, , Germany

Universitätsklinikum Mannheim GmbH

Mannheim, , Germany

Universitätsklinikum Münster

Münster, , Germany

Mathias-Spital Rheine

Rheine, , Germany

"Hippokratio" Hospital of Athens, 2nd Internal Medicine Clin

Athens, , Greece

General Hospital of Chest Diseases Sotiria

Athens, , Greece

University General Hospital of Heraklion

Heraklion, , Greece

University Hospital of Larisa, Oncology Clinic

Larissa, , Greece

General Hospital of Larissa

Larissa, , Greece

Metropolitan Hospital, Oncology Clinic

Neo Faliro, Athens, , Greece

General Hospital "G. Papageorgiou"

Thessaloniki, , Greece

National Koranyi TBC and Pulm. Internal Med. Clinic

Budapest, , Hungary

Semmelweis University

Budapest, , Hungary

Institute of Chest Diseases Csongrad County,Dpt. Pulmonology

Deszk, , Hungary

Pulmonology Institute of Veszprem County, Farkasgyepu

Farkasgyepü, , Hungary

Aladar Petz County Teaching Hospital, Dept. Pulmonology

Győr, , Hungary

Lung Hospital of Matra, Dept. Pulmonology

Mátraháza, , Hungary

Josa Andras Korhaz, Nyiregyhaza

Nyíregyháza, , Hungary

University of Pecs, 1st internal Med. Dept., Pulmonology

Pécs, , Hungary

Pest County Lung Hospital, Department No. 3

Törökbálint, , Hungary

Vikram Hospital

Bangalore, , India

V S Hospital

Chennai, , India

Dr. Kamakshi Memorial Hospital

Chennai, , India

Sri Ramachandra Medical College & Research Institute

Chennai, , India

M.S. Patel Cancer Hospital

Karamsad, , India

B. P .Poddar Hospital & Medical Research Ltd.

Kolkata, West Bengal, , India

Tata Memorial Hospital

Mumbai, , India

Ruby Hall Clinic

Pune, , India

St James's Hospital

Dublin, , Ireland

P.O. Bellaria IRCCS Istituto delle scienze Neurologiche di Bologna

Bologna, , Italy

ASST di Cremona

Cremona, , Italy

Spedali Riuniti di Livorno

Livorno, , Italy

Istituto Nazionale Tumori Fondazione Pascale

Napoli, , Italy

Istituto Oncologico Veneto IRCCS

Padua, , Italy

Azienda Ospedaliera di Parma

Parma, , Italy

Azienda Ospedaliera Universitaria Pisana

Pisa, , Italy

Istituto Clinico Humanitas

Rozzano (MI), , Italy

Ospedale San Vincenzo

Taormina (ME), , Italy

Ospedale Molinette, AO Città della Salute e della

Torino, , Italy

A. O. S. Maria della Misericordia

Udine, , Italy

Instituto Nacional de Cancerologia

México, , Mexico

Hospital y Clínica OCA S. A. de C. V.

Monterrey, , Mexico

Centro Hemato-Oncologico Privado de Toluca S.A. de C.V.

Toluca, , Mexico

Jeroen Bosch Ziekenhuis-Hertogenbosch

's-Hertogenbosch, , Netherlands

Rijnstate Hospital

Arnhem, , Netherlands

Amphia Ziekenhuis

Breda, , Netherlands

Catharina Ziekenhuis

Eindhoven, , Netherlands

METC Academisch Ziekenhuis Maastricht/Universiteit van Maastricht

Maastricht, , Netherlands

St. Antonius ziekenhuis, locatie Nieuwegein

Nieuwegein, , Netherlands

Erasmus Medisch Centrum

Rotterdam, , Netherlands

CHUC - Centro Hospitalar e Universitário de Coimbra, EPE

Coimbra, , Portugal

CHLN, EPE - Hospital de Santa Maria

Lisbon, , Portugal

IPO Lisboa Francisco Gentil, EPE

Lisbon, , Portugal

IPO Porto Francisco Gentil, EPE

Porto, , Portugal

Centro Hospitalar São João,EPE

Porto, , Portugal

Centro Hospitalar de Vila Nova de Gaia

Vila Nova de Gaia, , Portugal

National Cancer Centre

Singapore, , Singapore

Johns Hopkins Singapore International Medical Centre

Singapore, , Singapore

Chungbuk National University Hospital

Cheongju-si, , South Korea

Gachon University Gil Medical Center

Incheon, , South Korea

Gyeongsang National University Hospital

Jinju, , South Korea

Seoul National University Bundang Hospital

Seongnam, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea, Seoul St.Mary's Hospital

Seoul, , South Korea

The Catholic University of Korea, St.Vincent's Hospital

Suwon, , South Korea

Ulsan University Hospital

Ulsan, , South Korea

Hospital A Coruña

A Coruña, , Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Santa Creu i Sant Pau

Barcelona, , Spain

Hospital Clínico San Carlos

Madrid, , Spain

Hospital La Paz

Madrid, , Spain

Hospital Regional Universitario de Málaga

Málaga, , Spain

Hospital Virgen de la Victoria

Málaga, , Spain

Hospital Clínico de Valencia

Valencia, , Spain

Hospital Clínico Universitario Lozano Blesa

Zaragoza, , Spain

Chang Gung Memorial Hospital Chiayi

Chiayi City, , Taiwan

Buddhist Tzu Chi General Hospital

Chiayi City, , Taiwan

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

Koo Foundation Sun Yet-Sen Cancer Center

Taipei, , Taiwan

Taipe Veterans General Hospital

Taipei, , Taiwan

Chang Gung Memorial Hospital(TaoYuan)

Taoyuan District, , Taiwan

Akdeniz Universitesi Tip Fakultesi

Antalya, , Turkey (Türkiye)

Uludag Universitesi Tip Fakultesi, Bursa

Bursa, , Turkey (Türkiye)

Dicle Universitesi Tip Fakultesi

Diyarbakır, , Turkey (Türkiye)

Gaziantep Univ. Tip Fakultesi Tibbi Onkoloji Bilim Dali

Gaziantep, , Turkey (Türkiye)

Kartal Egitim Ve Arastirma Hastanesi

Istanbul, , Turkey (Türkiye)

Yedikule Gog. Hst. EAH

Istanbul, , Turkey (Türkiye)

Ege Universitesi Tip Fakultesi Tibbi Onkoloji Bilim Dali

Izmir, , Turkey (Türkiye)

Dr.Suat Seren EAH

Izmir, , Turkey (Türkiye)

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Royal Devon and Exeter Hospital

Exeter, , United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Harrogate District Hospital

Harrogate, , United Kingdom

Royal Free Hospital

London, , United Kingdom

The Royal Marsden Hospital

London, , United Kingdom

Maidstone Hospital, Kent Oncology Centre

Maidstone, , United Kingdom

Nottingham City Hospital

Nottingham, , United Kingdom

Scarborough Hospital

Scarborough, , United Kingdom

The Royal Marsden Hospital

Sutton, , United Kingdom

Countries

United States; Argentina; Austria; Canada; Chile; China; Denmark; France; Germany; Greece; Hungary; India; Ireland; Italy; Mexico; Netherlands; Portugal; Singapore; South Korea; Spain; Taiwan; Turkey (Türkiye); United Kingdom

References

Lu S, Li W, Zhou C, Hu CP, Qin S, Cheng G, Feng J, Wang J, Cseh A, Peil B, Gibson N, Ehrnrooth E, Zhang L. Afatinib vs erlotinib for second-line treatment of Chinese patients with advanced squamous cell carcinoma of the lung. Onco Targets Ther. 2018 Nov 30;11:8565-8573. doi: 10.2147/OTT.S161506. eCollection 2018.

Reference Type: DERIVED

PMID: 30573970 (View on PubMed)

Goss GD, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Goker E, Georgoulias V, Li W, Guclu S, Isla D, Min YJ, Morabito A, Ardizzoni A, Gadgeel SM, Fulop A, Buhnemann C, Gibson N, Kramer N, Solca F, Cseh A, Ehrnrooth E, Soria JC. Association of ERBB Mutations With Clinical Outcomes of Afatinib- or Erlotinib-Treated Patients With Lung Squamous Cell Carcinoma: Secondary Analysis of the LUX-Lung 8 Randomized Clinical Trial. JAMA Oncol. 2018 Sep 1;4(9):1189-1197. doi: 10.1001/jamaoncol.2018.0775.

Reference Type: DERIVED

PMID: 29902295 (View on PubMed)

Gadgeel S, Goss G, Soria JC, Felip E, Georgoulias V, Lu S, Cobo M, Syrigos K, Lee KH, Goker E, Guclu SZ, Isla D, Morabito A, Dupuis N, Buhnemann C, Kramer N, Solca F, Ehrnrooth E, Ardizzoni A. Evaluation of the VeriStrat(R) serum protein test in patients with advanced squamous cell carcinoma of the lung treated with second-line afatinib or erlotinib in the phase III LUX-Lung 8 study. Lung Cancer. 2017 Jul;109:101-108. doi: 10.1016/j.lungcan.2017.05.010. Epub 2017 May 11.

Reference Type: DERIVED

PMID: 28577938 (View on PubMed)

Soria JC, Felip E, Cobo M, Lu S, Syrigos K, Lee KH, Goker E, Georgoulias V, Li W, Isla D, Guclu SZ, Morabito A, Min YJ, Ardizzoni A, Gadgeel SM, Wang B, Chand VK, Goss GD; LUX-Lung 8 Investigators. Afatinib versus erlotinib as second-line treatment of patients with advanced squamous cell carcinoma of the lung (LUX-Lung 8): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2015 Aug;16(8):897-907. doi: 10.1016/S1470-2045(15)00006-6. Epub 2015 Jul 5.

Reference Type: DERIVED

PMID: 26156651 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2011-002380-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1200.125

Identifier Type: -

Identifier Source: org_study_id