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

Carcinoma, Non-Small-Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01523587
• Other study ID #: 1200.125
• Secondary ID: 2011-002380-24
• Status: Completed
• Phase: Phase 3
• Start date: March 5, 2012
• Est. completion date: December 27, 2017

Study information

• Verified date: February 2019
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 795
• Est. completion date: December 27, 2017
• Est. primary completion date: October 21, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• afatinib
Afatinib taken once daily, continuously until disease progression or unacceptable toxicity.
• erlotinib
erlotinib taken once daily

Locations

Country	Name	City	State
Argentina	Instituto Medico Especializado Alexander Fleming	Ciudad Autonoma de Bs As
Argentina	Clínica Colombo S.A.	Cordoba
Argentina	Instituto Oncologico de Cordoba	Cordoba
Argentina	Centro Oncologico de Rosario	Rosario
Argentina	Centro Oncologico CAIPO	San Miguel de Tucuman
Austria	Medical University of Innsbruck	Innsbruck
Austria	LKH Leoben	Leoben
Austria	AKH d. Stadt Linz, Pulmologie	Linz
Austria	SMZ Baumgartner Hoehe Otto Wagner Spital	Wien
Canada	Kingston General Hospital	Kingston	Ontario
Canada	Montreal General Hospital - McGill University Health Centre	Montreal	Quebec
Canada	Royal Victoria Hospital	Montreal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	BC Cancer Agency - Fraser Valley Centre	Surrey	British Columbia
Chile	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
China	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	Jiangsu Cancer Hospital	Nanjing
China	the 81th Hospital of PLA	Nanjing
China	Shanghai Chest Hospital	Shanghai
China	Shanghai Pulmonary Hospital	Shanghai
Denmark	Herlev Hospital	Herlev
Denmark	Næstved Sygehus	Næstved
Denmark	Odense Universitetshospital	Odense C
France	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	Creteil
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 Cedex 20
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
Germany	Zentralklinik Bad Berka GmbH	Bad Berka
Germany	Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH	Essen
Germany	Klinikum Esslingen GmbH	Esslingen
Germany	Universitätsklinikum Frankfurt	Frankfurt am Main
Germany	Universitätsklinikum Freiburg	Freiburg
Germany	Universitätsklinikum Hamburg-Eppendorf	Hamburg
Germany	Lungenklinik Hemer	Hemer
Germany	Universitätsklinikum Mannheim GmbH	Mannheim
Germany	Universitätsklinikum Münster	Münster
Germany	Mathias-Spital Rheine	Rheine
Greece	"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	General Hospital of Larissa	Larisa
Greece	University Hospital of Larisa, Oncology Clinic	Larisa
Greece	Metropolitan Hospital, Oncology Clinic	Neo Faliro, Athens
Greece	General Hospital "G. Papageorgiou"	Thessaloniki
Hungary	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	Györ
Hungary	Lung Hospital of Matra, Dept. Pulmonology	Matrahaza
Hungary	Josa Andras Korhaz, Nyiregyhaza	Nyiregyhaza
Hungary	University of Pecs, 1st internal Med. Dept., Pulmonology	Pecs
Hungary	Pest County Lung Hospital, Department No. 3	Törökbalint
India	Vikram Hospital	Bangalore
India	Dr. Kamakshi Memorial Hospital	Chennai
India	Sri Ramachandra Medical College & Research Institute	Chennai
India	V S Hospital	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
Ireland	St James's Hospital	Dublin 8
Italy	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	Padova
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
Korea, Republic of	Chungbuk National University Hospital	Cheongju
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Gyeongsang National University Hospital	Jinju
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	The Catholic University of Korea, Seoul St.Mary's Hospital	Seoul
Korea, Republic of	The Catholic University of Korea, St.Vincent's Hospital	Suwon
Korea, Republic of	Ulsan University Hospital	Ulsan
Mexico	Instituto Nacional de Cancerologia	Mexico
Mexico	Hospital y Clínica OCA S. A. de C. V.	Monterrey
Mexico	Centro Hemato-Oncologico Privado de Toluca S.A. de C.V.	Toluca
Netherlands	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
Portugal	CHUC - Centro Hospitalar e Universitário de Coimbra, EPE	Coimbra
Portugal	CHLN, EPE - Hospital de Santa Maria	Lisboa
Portugal	IPO Lisboa Francisco Gentil, EPE	Lisboa
Portugal	Centro Hospitalar São João,EPE	Porto
Portugal	IPO Porto Francisco Gentil, EPE	Porto
Portugal	Centro Hospitalar de Vila Nova de Gaia	Vila Nova de Gaia
Singapore	Johns Hopkins Singapore International Medical Centre	Singapore
Singapore	National Cancer Centre	Singapore
Spain	Hospital A Coruña	A Coruña
Spain	Hospital Santa Creu i Sant Pau	Barcelona
Spain	Hospital Vall d'Hebron	Barcelona
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital La Paz	Madrid
Spain	Hospital Regional Universitario de Málaga	Malaga
Spain	Hospital Virgen de la Victoria	Malaga
Spain	Hospital Clínico de Valencia	Valencia
Spain	Hospital Clínico Universitario Lozano Blesa	Zaragoza
Taiwan	Buddhist Tzu Chi General Hospital	Chiayi
Taiwan	Chang Gung Memorial Hospital Chiayi	Chiayi
Taiwan	Kaohsiung Chang Gung Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Koo Foundation Sun Yet-Sen Cancer Center	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipe Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital(TaoYuan)	Taoyuan
Turkey	Akdeniz Universitesi Tip Fakultesi	Antalya
Turkey	Uludag Universitesi Tip Fakultesi, Bursa	Bursa
Turkey	Dicle Universitesi Tip Fakultesi	Diyarbakir
Turkey	Gaziantep Univ. Tip Fakultesi Tibbi Onkoloji Bilim Dali	Gaziantep
Turkey	Kartal Egitim Ve Arastirma Hastanesi	Istanbul
Turkey	Yedikule Gog. Hst. EAH	Istanbul
Turkey	Dr.Suat Seren EAH	Izmir
Turkey	Ege Universitesi Tip Fakultesi Tibbi Onkoloji Bilim Dali	Izmir
United Kingdom	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 States	Billings Clinic Cancer Center	Billings	Montana
United States	Boca Raton Reginl Hospital-Lynn Cancer Institute	Boca Raton	Florida
United States	Montefiore Medical Center	Bronx	New York
United States	Montefiore Medical Center	Bronx	New York
United States	Fletcher Allen Health Care	Burlington	Vermont
United States	Lahey Clinic	Burlington	Massachusetts
United States	Ironwood Cancer and Research Centers	Chandler	Arizona
United States	Blue Ridge Cancer Care	Christiansburg	Virginia
United States	Cleveland Clinic	Cleveland	Ohio
United States	Mid Ohio Oncology/Hematology, Inc	Columbus	Ohio
United States	The Ohio State University Wexner Medical Center	Columbus	Ohio
United States	Cancer Center of Cookeville Regional Medical Center	Cookeville	Tennessee
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Oncology Hematology Associates of Norhtern Pennsylvania, PC	DuBois	Pennsylvania
United States	Queens Medical Associates	Fresh Meadows	New York
United States	Memorial Healthcare System	Hollywood	Florida
United States	University of California	La Jolla	California
United States	Cancer Care of North Florida, PA	Lake City	Florida
United States	Commonwealth Hematology-Oncology, PC	Lawrence	Massachusetts
United States	University of Louisville	Louisville	Kentucky
United States	West Jefferson General Hospital and Cancer Clinic	Marrero	Louisiana
United States	Illinois Cancer Specialists	Niles	Illinois
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Paris Cancer Center (PCC), Texas Oncology	Paris	Texas
United States	Kimmel Cancer Center	Philadelphia	Pennsylvania
United States	Temple University Cancer Center	Philadelphia	Pennsylvania
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Sutter Medical Group	Sacramento	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Cancer Therapy and Research at UTHSCSA	San Antonio	Texas
United States	Orchard Healthcare Research Inc	Skokie	Illinois
United States	Spartanburg Regional Medical Center	Spartanburg	South Carolina
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Argentina,  Austria,  Canada,  Chile,  China,  Denmark,  France,  Germany,  Greece,  Hungary,  India,  Ireland,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Portugal,  Singapore,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival, Based on Central Independent Review as Determined by Response Evaluation Criteria in Solid Tumours 1.1	Progression Free Survival (PFS) was defined as the time from randomization to disease progression (or death if the patient died before progression) by central independent review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. RECIST is a set of published rules that define when tumors in cancer patients improve ("respond"), stay the same ("stabilize") or worsen ("progress") during treatment. Per RECIST v1.1 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	First treatment administration up until cut off date of 02 March 2015 (up to 1058 days).
Secondary	Overall Survival	Overall Survival is defined as the time from randomisation to death. It was a key secondary endpoint.	From first drug administration from 9 April 2012 until study closure on 27 Dec 2017 (approximately 2089 days).
Secondary	Number of Participants With Objective Response According to RECIST 1.1	A patient with a best overall response of Complete Responder (CR) or Partial Responder (PR) was considered to show objective response to study medication. For patients with an objective response, time to objective response was defined as the time from randomization to the first objective response; duration of objective response was defined as the time from the first objective response to progression (or death if the patient died before progression). Per RECIST v1.1 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	First treatment administration up until cut off date of 02 March 2015 (up to 1058 days).
Secondary	Number of Participants With Disease Control According to RECIST 1.1	Disease control was assessed based on Independent Radiologic Review (IRR) and investigator assessment. A patient with a best overall response of CR, PR, or Stable Disease (SD) was considered to have disease control. Patients with no baseline target lesions who had no evidence of disease progression in their non-target lesions and had no new lesions were considered to have disease control. Per RECIST v1.1 for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	First treatment administration up until cut off date of 02 March 2015 (up to 1058 days).
Secondary	Tumour Shrinkage	Maximum percentage decrease from baseline in the sum of target lesion diameters following independent review. The change in the size (i.e. the sum of diameters (SOD)) of target lesions from baseline was derived. Tumour shrinkage for each patient was measured (based on Independent Radiologic Review (IRR)) as the minimum SOD of target lesions after randomisation.; A negative percentage indicates decrease from baseline; positive numbers indicate an increase of tumour size. The mean maximum decrease from baseline of +5 and +9.4 reflect an average increase in tumour size.; Post-baseline mean is adjusted for baseline sum of diameters and race.	First treatment administration up until cut off date of 02 March 2015 (up to 1058 days).
Secondary	Number of Participants With Status Change in Cough, Dyspnoea and Pain Related Items Over Time in Health Related Quality of Life Questionnaire	Health-related quality of life (HRQoL) was measured with the following multi-dimensional questionnaires: the european organization for research and treatment of cancer (eortc) quality of life questionnaire (QLQ-C30) questionnaire and its lung cancer specific supplementary module EORTC QLQ-LC13 and the EQ-5D health status self-assessment questionnaire. The questionnaires were assessed at the first visit of each treatment course, at end of treatment (EOT) and follow up prior to clinical assessment. The results displayed show number of patients with improvement in the relevant criteria. For each of the summary scales and items measuring cough, dyspnoea and pain, the two treatment arms were compared in terms of: The number of patients that were improved: Change in cough; dyspnoea and pain scores over time.	From first drug administration from 9 April 2012 until study closure on 27 Dec 2017 (approximately 2089 days).
Secondary	Summary of Time to Deterioration in Coughing, Dyspnoea and Pain.	Health-related quality of life (HRQoL) was measured with the following multi-dimensional questionnaires: the EORTC QLQ-C30. The questionnaires were assessed at the first visit of each treatment course. For each of the summary scales and items measuring cough, dyspnoea and pain, the two treatment arms were compared in terms of: Time to deterioration.	From first drug administration from 9 April 2012 until study closure on 27 Dec 2017 (approximately 2089 days).
Secondary	Change in Score Over Time in Coughing,Dyspnoea and Pain	Health related quality of life (HRQoL) was measured with the following multi dimensional questionnaires: the EORTC QLQ-C30. The questionnaires were assessed at the first visit of each treatment course. For each of the summary scales and items measuring cough, dyspnoea and pain, the two treatment arms were compared in terms of change in score over time, adjusted for baseline score and race.; Questionnaires have items relating to Cough, Dyspnoea and Pain. Overall Scores are transformed to a standardised scale of 0 to 100 with the larger value indicating a worse outcome. A change of (+/-) 10 points is considered to be relevant.; The change in cough, dyspnea and pain will be assessed using a mixed effects growth curve model with the average profile over time for each endpoint described by a piecewise linear model (presented as post baseline in data table). Post-baseline mean is adjusted for baseline and race.	From first drug administration from 9 April 2012 until study closure on 27 Dec 2017 (approximately 2089 days).

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