Clinical trial NCT01466660: LUX-Lung 7: A Phase IIb Trial of Afatinib(BIBW2992) Versus Gefitinib for the Treatment of 1st Line EGFR Mutation Positive Adenocarcinoma of the Lung
Official title: LUX-Lung 7: A Randomised, Open-label Phase IIb Trial of Afatinib Versus Gefitinib as First-line Treatment of Patients With EGFR Mutation Positive Advanced Adenocarcinoma of the Lung
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lung Neoplasms
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2011-11-08
Enrollment: 319
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomised, open-label, phase IIb trial of afatinib to compare to gefitinib in first-line treatment setting with patients who are having epidermal growth factor receptor mutation positive advanced adenocarcinoma of the lung.


Eligibility criteria: Inclusion criteria:

1. Pathologically confirmed diagnosis of Stage IIIB / IV adenocarcinoma of the lung.
2. Documented activating epidermal growth factor receptor mutation (Del19 and/or L858R) with tumour tissues.
3. At least one measurable lesion according to response evaluation criteria in solid tumours version 1.1
4. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
5. Age \>= 18 years.
6. Adequate organ function as defined by the following criteria:

Serum aspartate transaminase(AST) and serum alanine transaminase(ALT) =\< 3 x upper limit of normal (ULN), or AST and ALT =\<5 x ULN if liver function abnormalities are due to underlying malignancy Total serum bilirubin =\<1.5 x ULN Absolute neutrophil count (ANC) \>=1.5 x 109/L Creatinine clearance \> 45ml / min Platelets \>= 75 x 109/L

Exclusion criteria:

1. Prior systemic chemotherapy for stage IIIB or IV non-small cell lung cancer. Neo-/adjuvant chemotherapy, chemoradiation or radiotherapy is permitted if at least 12 months has elapsed prior to disease progression.
2. Prior treatment with epidermal growth factor receptor targeting small molecules or antibodies.
3. Major surgery within 4 weeks of study randomisation.
4. Active brain metastases
5. Meningeal carcinomatosis.
6. Previous or concomitant malignancies at other sites, except effectively treated non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ or effectively treated malignancy that has been in remission for more than 3 years and is considered to be cured in the opinion of investigator.
7. Known pre-existing interstitial lung disease.
8. Clinically relevant cardiovascular abnormalities as judged by the investigator.
9. Cardiac left ventricular function with resting ejection fraction of less than institutional lower limit of normal.
10. Women of child-bearing potential (WOCBP) 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.
11. Pregnancy or breast-feeding.
12. Active hepatitis and/or known HIV carrier
13. Any prohibited concomitant medications for therapy with afatinib or gefitinib

Primary outcomes:
measure: Progression-free Survival
timeFrame: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.
measure: Time to Treatment Failure (TTF) (Main Overall Survival Analysis Cut-off Date, 08 April 2016)
timeFrame: From first drug administration until last drug administration, up to 1482 days
measure: Overall Survival
timeFrame: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on death, up to 2465 days.
Secondary outcomes:
measure: Objective Response Rate
timeFrame: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days.
measure: Time to Objective Response
timeFrame: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days.
measure: Duration of Objective Response
timeFrame: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression, further anti-cancer treatment and death, up to 2465 days.
measure: Disease Control
timeFrame: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.
measure: Duration of Disease Control
timeFrame: From first drug administration until 28 days after last drug administration + Follow-Up period for collecting information on disease progression or death, up to 2465 days.
measure: Tumour Shrinkage (Main Overall Survival Analysis Cut-off Date, 08 April 2016)
timeFrame: From first drug administration until last drug administration, up to 1482 days
measure: Health-related Quality of Life (Primary Analysis Cut-off Date, 21 August 2015)
timeFrame: Every 8 weeks, up to 56 weeks
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Chris Obrien Lifehouse
state: New South Wales
city: Kogarah
country: Australia
facility: St George Hospital
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: South Brisbane
country: Australia
facility: Haematology & Oncology Clinics of Australasia (HOCA)
state: Queensland
city: Box Hill
country: Australia
facility: Box Hill Hospital
state: Victoria
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Nedlands
country: Australia
facility: Sir Charles Gairdner Hospital
state: Western Australia
city: Edmonton
country: Canada
facility: Cross Cancer Institute (University of Alberta)
state: Alberta
city: Surrey
country: Canada
facility: British Columbia Cancer Agency (BCCA) - Fraser Valley Cancer
state: British Columbia
city: Vancouver
country: Canada
facility: BC Cancer Agency - Vancouver
state: British Columbia
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Montreal
country: Canada
facility: Montreal General Hospital - McGill University Health Centre
state: Quebec
city: Beijing
country: China
facility: Cancer Hospital of Chinese Academy of Medical Science
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Guangzhou
country: China
facility: Sun Yat-Sen University Cancer Center
city: Nan Ning
country: China
facility: The Affiliated Cancer Hospital, Guangxi Medical University
city: Shanghai
country: China
facility: Shanghai Chest Hospital
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University
city: Shenyang
country: China
facility: The First Hospital of Chinese Medical University
city: Bayonne
country: France
facility: CTR Oncologie du Pays Basque, Onco, Bayonne
city: Caen
country: France
facility: CTR François Baclesse
city: Créteil
country: France
facility: HOP Intercommunal
city: La Tronche
country: France
facility: HOP Michallon
city: Limoges Cedex
country: France
facility: HOP Dupuytren 1
city: Lyon
country: France
facility: CTR Leon Berard
city: Saint Herblain
country: France
facility: CTR René Gauducheau
city: St-Pierre - La Réunion
country: France
facility: HOP Sud-Réunion, Pneumo, Saint Pierre
city: Essen
country: Germany
facility: Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH
city: Esslingen
country: Germany
facility: Klinikum Esslingen GmbH
city: Mainz
country: Germany
facility: Universitätsmedizin der Johannes Gutenberg-Universität Mainz
city: Hongkong
country: Hong Kong
facility: Queen Mary Hospital
city: Shatin
country: Hong Kong
facility: Prince of Wales Hospital
city: Dublin 9
country: Ireland
facility: Beaumont Hospital
city: Dublin
country: Ireland
facility: St James's Hospital
city: Cheongju
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Radiumhospitalet
city: Singapore
country: Singapore
facility: National Cancer Centre
city: Singapore
country: Singapore
facility: Johns Hopkins Singapore International Medical Center
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Málaga
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Virgen del Rocío
city: Göteborg
country: Sweden
facility: Sahlgrenska US, Göteborg
city: Linköping
country: Sweden
facility: Universitetssjukhuset, Linköping
city: Lund
country: Sweden
facility: Skånes universitetssjukhus, Lund
city: Stockholm
country: Sweden
facility: Karolinska Univ. sjukhuset
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: NCKUH
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipe Veterans General Hospital
city: Tao-Yuan
country: Taiwan
facility: Chang Gung Memorial Hospital(Linkou)
city: Aberdeen
country: United Kingdom
facility: Aberdeen Royal Infirmary
city: Birmingham
country: United Kingdom
facility: Birmingham City Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Guildford
country: United Kingdom
facility: Royal Surrey County Hospital
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: 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.
citation: Paz-Ares L, Tan EH, O'Byrne K, Zhang L, Hirsh V, Boyer M, Yang JC, Mok T, Lee KH, Lu S, Shi Y, Lee DH, Laskin J, Kim DW, Laurie SA, Kolbeck K, Fan J, Dodd N, Marten A, Park K. Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial. Ann Oncol. 2017 Feb 1;28(2):270-277. doi: 10.1093/annonc/mdw611.
citation: Park K, Tan EH, O'Byrne K, Zhang L, Boyer M, Mok T, Hirsh V, Yang JC, Lee KH, Lu S, Shi Y, Kim SW, Laskin J, Kim DW, Arvis CD, Kolbeck K, Laurie SA, Tsai CM, Shahidi M, Kim M, Massey D, Zazulina V, Paz-Ares L. Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-small-cell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol. 2016 May;17(5):577-89. doi: 10.1016/S1470-2045(16)30033-X. Epub 2016 Apr 12.