Clinical trial NCT01523587: 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
Official title: LUX-Lung 8: A Randomized, Open-label Phase III Trial of Afatinib Versus Erlotinib in Patients With Advanced Squamous Cell Carcinoma of the Lung as Second-line Therapy Following First-line Platinum-based Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2012-02-01
Enrollment: 795
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Progression-free Survival, Based on Central Independent Review as Determined by Response Evaluation Criteria in Solid Tumours 1.1
timeFrame: First treatment administration up until cut off date of 02 March 2015 (up to 1058 days).
Secondary outcomes:
measure: Overall Survival
timeFrame: From first drug administration from 9 April 2012 until study closure on 27 Dec 2017 (approximately 2089 days).
measure: Number of Participants With Objective Response According to RECIST 1.1
timeFrame: First treatment administration up until cut off date of 02 March 2015 (up to 1058 days).
measure: Number of Participants With Disease Control According to RECIST 1.1
timeFrame: First treatment administration up until cut off date of 02 March 2015 (up to 1058 days).
measure: Tumour Shrinkage
timeFrame: First treatment administration up until cut off date of 02 March 2015 (up to 1058 days).
measure: Number of Participants With Status Change in Cough, Dyspnoea and Pain Related Items Over Time in Health Related Quality of Life Questionnaire
timeFrame: From first drug administration from 9 April 2012 until study closure on 27 Dec 2017 (approximately 2089 days).
measure: Summary of Time to Deterioration in Coughing, Dyspnoea and Pain.
timeFrame: From first drug administration from 9 April 2012 until study closure on 27 Dec 2017 (approximately 2089 days).
measure: Change in Score Over Time in Coughing,Dyspnoea and Pain
timeFrame: From first drug administration from 9 April 2012 until study closure on 27 Dec 2017 (approximately 2089 days).
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer and Research Centers
state: Arizona
city: La Jolla
country: United States
facility: University of California
state: California
city: Sacramento
country: United States
facility: Sutter Medical Group
state: California
city: Boca Raton
country: United States
facility: Boca Raton Reginl Hospital-Lynn Cancer Institute
state: Florida
city: Hollywood
country: United States
facility: Memorial Healthcare System
state: Florida
city: Lake City
country: United States
facility: Cancer Care of North Florida, PA
state: Florida
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc
state: Illinois
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Marrero
country: United States
facility: West Jefferson General Hospital and Cancer Clinic
state: Louisiana
city: Burlington
country: United States
facility: Lahey Clinic
state: Massachusetts
city: Lawrence
country: United States
facility: Commonwealth Hematology-Oncology, PC
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Billings
country: United States
facility: Billings Clinic Cancer Center
state: Montana
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Fresh Meadows
country: United States
facility: Queens Medical Associates
state: New York
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Columbus
country: United States
facility: Mid Ohio Oncology/Hematology, Inc
state: Ohio
city: Portland
country: United States
facility: Kaiser Permanente Northwest
state: Oregon
city: DuBois
country: United States
facility: Oncology Hematology Associates of Norhtern Pennsylvania, PC
state: Pennsylvania
city: Philadelphia
country: United States
facility: Kimmel Cancer Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple University Cancer Center
state: Pennsylvania
city: Spartanburg
country: United States
facility: Spartanburg Regional Medical Center
state: South Carolina
city: Cookeville
country: United States
facility: Cancer Center of Cookeville Regional Medical Center
state: Tennessee
city: Paris
country: United States
facility: Paris Cancer Center (PCC), Texas Oncology
state: Texas
city: San Antonio
country: United States
facility: Cancer Therapy and Research at UTHSCSA
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care
state: Vermont
city: Christiansburg
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Ciudad Autonoma de Bs As
country: Argentina
facility: Instituto Medico Especializado Alexander Fleming
city: Cordoba
country: Argentina
facility: Instituto Oncologico de Cordoba
city: Cordoba
country: Argentina
facility: Clínica Colombo S.A.
city: Rosario
country: Argentina
facility: Centro Oncologico de Rosario
city: San Miguel de Tucuman
country: Argentina
facility: Centro Oncologico CAIPO
city: Innsbruck
country: Austria
facility: Medical University of Innsbruck
city: Leoben
country: Austria
facility: LKH Leoben
city: Linz
country: Austria
facility: AKH d. Stadt Linz, Pulmologie
city: Wien
country: Austria
facility: SMZ Baumgartner Hoehe Otto Wagner Spital
city: Surrey
country: Canada
facility: BC Cancer Agency - Fraser Valley Centre
state: British Columbia
city: Kingston
country: Canada
facility: Kingston General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Montreal
country: Canada
facility: Royal Victoria Hospital
state: Quebec
city: Montreal
country: Canada
facility: Montreal General Hospital - McGill University Health Centre
state: Quebec
city: Antofagasta
country: Chile
facility: Centro Oncologico Antofagasta
city: Providencia, Santiago
country: Chile
facility: Instituto de Terapias Oncologicas Providencia
city: Recoleta, Santiago De Chile
country: Chile
facility: Centro Internacional de Estudios Clinicos - CIEC
city: Vitacura
country: Chile
facility: Orlandi Oncologia
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Beijing
country: China
facility: Beijing Hospital
city: Changchun
country: China
facility: First Hospital of Jilin University
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
city: Nanjing
country: China
facility: the 81th Hospital of PLA
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Næstved
country: Denmark
facility: Næstved Sygehus
city: Odense C
country: Denmark
facility: Odense Universitetshospital
city: Angers
country: France
facility: HOP d'Angers
city: Bordeaux
country: France
facility: INS Bergonié
city: Caen
country: France
facility: HOP Côte de Nacre
city: Chauny
country: France
facility: HOP de Chauny
city: Clermont Ferrand
country: France
facility: HOP Gabriel-Montpied
city: Creteil
country: France
facility: HOP de Creteil, Pneumo, Creteil
city: Le Mans
country: France
facility: HOP Le Mans
city: Lille
country: France
facility: CTR Oscar Lambret, Cancéro, Lille
city: Lille
country: France
facility: HOP Calmette
city: Marseille Cedex 20
country: France
facility: HOP Nord
city: Marseille
country: France
facility: INS Paoli-Calmettes
city: Mulhouse
country: France
facility: HOP de Mulhouse, Onco, Mulhouse
city: Paris
country: France
facility: HOP Cochin
city: Paris
country: France
facility: HOP Val de Grâce, Onco, Paris
city: Reims
country: France
facility: INS Jean Godinot, Onco, Reims
city: Rennes
country: France
facility: HOP de Rennes, Pneumo, Rennes
city: Saint Quentin
country: France
facility: HOP Saint Quentin, Onco, Saint Quentin
city: Strasbourg
country: France
facility: HOP Civil
city: Suresnes
country: France
facility: HOP Foch
city: Villejuif
country: France
facility: INS Gustave Roussy
city: Bad Berka
country: Germany
facility: Zentralklinik Bad Berka GmbH
city: Essen
country: Germany
facility: Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
city: Esslingen
country: Germany
facility: Klinikum Esslingen GmbH
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf
city: Hemer
country: Germany
facility: Lungenklinik Hemer
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim GmbH
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Rheine
country: Germany
facility: Mathias-Spital Rheine
city: Athens
country: Greece
facility: "Hippokratio" Hospital of Athens, 2nd Internal Medicine Clin
city: Athens
country: Greece
facility: General Hospital of Chest Diseases Sotiria
city: Heraklion
country: Greece
facility: University General Hospital of Heraklion
city: Larisa
country: Greece
facility: University Hospital of Larisa, Oncology Clinic
city: Larisa
country: Greece
facility: General Hospital of Larissa
city: Neo Faliro, Athens
country: Greece
facility: Metropolitan Hospital, Oncology Clinic
city: Thessaloniki
country: Greece
facility: General Hospital "G. Papageorgiou"
city: Budapest
country: Hungary
facility: National Koranyi TBC and Pulm. Internal Med. Clinic
city: Budapest
country: Hungary
facility: Semmelweis University
city: Deszk
country: Hungary
facility: Institute of Chest Diseases Csongrad County,Dpt. Pulmonology
city: Farkasgyepü
country: Hungary
facility: Pulmonology Institute of Veszprem County, Farkasgyepu
city: Györ
country: Hungary
facility: Aladar Petz County Teaching Hospital, Dept. Pulmonology
city: Matrahaza
country: Hungary
facility: Lung Hospital of Matra, Dept. Pulmonology
city: Nyiregyhaza
country: Hungary
facility: Josa Andras Korhaz, Nyiregyhaza
city: Pecs
country: Hungary
facility: University of Pecs, 1st internal Med. Dept., Pulmonology
city: Törökbalint
country: Hungary
facility: Pest County Lung Hospital, Department No. 3
city: Bangalore
country: India
facility: Vikram Hospital
city: Chennai
country: India
facility: V S Hospital
city: Chennai
country: India
facility: Dr. Kamakshi Memorial Hospital
city: Chennai
country: India
facility: Sri Ramachandra Medical College & Research Institute
city: Karamsad
country: India
facility: M.S. Patel Cancer Hospital
city: Kolkata, West Bengal
country: India
facility: B. P .Poddar Hospital & Medical Research Ltd.
city: Mumbai
country: India
facility: Tata Memorial Hospital
city: Pune
country: India
facility: Ruby Hall Clinic
city: Dublin 8
country: Ireland
facility: St James's Hospital
city: Bologna
country: Italy
facility: P.O. Bellaria IRCCS Istituto delle scienze Neurologiche di Bologna
city: Cremona
country: Italy
facility: ASST di Cremona
city: Livorno
country: Italy
facility: Spedali Riuniti di Livorno
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori Fondazione Pascale
city: Padova
country: Italy
facility: Istituto Oncologico Veneto IRCCS
city: Parma
country: Italy
facility: Azienda Ospedaliera di Parma
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
city: Rozzano (MI)
country: Italy
facility: Istituto Clinico Humanitas
city: Taormina (ME)
country: Italy
facility: Ospedale San Vincenzo
city: Torino
country: Italy
facility: Ospedale Molinette, AO Città della Salute e della
city: Udine
country: Italy
facility: A. O. S. Maria della Misericordia
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Jinju
country: Korea, Republic of
facility: Gyeongsang National University Hospital
city: Seongnam
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea, Seoul St.Mary's Hospital
city: Suwon
country: Korea, Republic of
facility: The Catholic University of Korea, St.Vincent's Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Mexico
country: Mexico
facility: Instituto Nacional de Cancerologia
city: Monterrey
country: Mexico
facility: Hospital y Clínica OCA S. A. de C. V.
city: Toluca
country: Mexico
facility: Centro Hemato-Oncologico Privado de Toluca S.A. de C.V.
city: 's-HERTOGENBOSCH
country: Netherlands
facility: Jeroen Bosch Ziekenhuis-Hertogenbosch
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Maastricht
country: Netherlands
facility: METC Academisch Ziekenhuis Maastricht/Universiteit van Maastricht
city: Nieuwegein
country: Netherlands
facility: St. Antonius ziekenhuis, locatie Nieuwegein
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Coimbra
country: Portugal
facility: CHUC - Centro Hospitalar e Universitário de Coimbra, EPE
city: Lisboa
country: Portugal
facility: CHLN, EPE - Hospital de Santa Maria
city: Lisboa
country: Portugal
facility: IPO Lisboa Francisco Gentil, EPE
city: Porto
country: Portugal
facility: IPO Porto Francisco Gentil, EPE
city: Porto
country: Portugal
facility: Centro Hospitalar São João,EPE
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Singapore
country: Singapore
facility: Johns Hopkins Singapore International Medical Centre
city: A Coruña
country: Spain
facility: Hospital A Coruña
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Santa Creu i Sant Pau
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital La Paz
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Malaga
country: Spain
facility: Hospital Virgen de la Victoria
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Zaragoza
country: Spain
facility: Hospital Clínico Universitario Lozano Blesa
city: Chiayi
country: Taiwan
facility: Chang Gung Memorial Hospital Chiayi
city: Chiayi
country: Taiwan
facility: Buddhist Tzu Chi General Hospital
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Chang Gung Memorial Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Koo Foundation Sun Yet-Sen Cancer Center
city: Taipei
country: Taiwan
facility: Taipe Veterans General Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital(TaoYuan)
city: Antalya
country: Turkey
facility: Akdeniz Universitesi Tip Fakultesi
city: Bursa
country: Turkey
facility: Uludag Universitesi Tip Fakultesi, Bursa
city: Diyarbakir
country: Turkey
facility: Dicle Universitesi Tip Fakultesi
city: Gaziantep
country: Turkey
facility: Gaziantep Univ. Tip Fakultesi Tibbi Onkoloji Bilim Dali
city: Istanbul
country: Turkey
facility: Kartal Egitim Ve Arastirma Hastanesi
city: Istanbul
country: Turkey
facility: Yedikule Gog. Hst. EAH
city: Izmir
country: Turkey
facility: Ege Universitesi Tip Fakultesi Tibbi Onkoloji Bilim Dali
city: Izmir
country: Turkey
facility: Dr.Suat Seren EAH
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Exeter
country: United Kingdom
facility: Royal Devon and Exeter Hospital
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: Harrogate
country: United Kingdom
facility: Harrogate District Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: The Royal Marsden Hospital
city: Maidstone
country: United Kingdom
facility: Maidstone Hospital, Kent Oncology Centre
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Scarborough
country: United Kingdom
facility: Scarborough Hospital
city: Sutton
country: United Kingdom
facility: The Royal Marsden Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.