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

NCT01466660 | Completed Phase 2 Results

• 2 other identifiers: 1200.1232011-001814-33
• Study Type: interventional
• Target: 319
• Locations: 14 countries
• Sites: 63

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.

Conditions

Lung Neoplasms

Outcome Measures

Primary Outcomes (3)

• Progression-free Survival

  Progression-free survival (PFS) defined as the time from date of randomisation to date of disease progression, or date of death if a patient died earlier. Participants with no event (Disease progression (PD) or death) were censored. PD was primarily evaluated for the primary analysis by an independent central imaging review according to Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. Per RECIST version 1.1. for target lesions and assessed by Computed Tomography (CT)-scan or Magnetic Resonance Imaging (MRI): PD, At least a 20% increase in the sum of the longest diameter (SoD) of target lesions taking as reference the smallest SoD of target lesions recorded since the treatment started, together with an absolute increase in the SoD of target lesions of at least 5 millimetre (mm) or the appearance of one or more new lesions. For the final analysis (analysis cut-off date 12 April 2019) status and date of PD were determined by investigator assessment.

  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.

• Time to Treatment Failure (TTF) (Main Overall Survival Analysis Cut-off Date, 08 April 2016)

  Time to Treatment Failure (TTF) which was the time from the date of randomisation to the date of i.e. permanent treatment discontinuation for any reason.

  From first drug administration until last drug administration, up to 1482 days

• Overall Survival

  Overall survival (OS) which was defined as the time from the date of randomisation to the date of death. Participants for whom there is no evidence of death at the time of the analysis will be censored at the date that they were last known to be alive.

  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 (7)

• Objective Response Rate

  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.

• Time to Objective Response

  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.

• Duration of Objective Response

  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.

• Disease Control

  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.

• Duration of Disease Control

  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.

Study Arms (2)

afatinib

EXPERIMENTAL

afatinib once daily.

Drug: Afatinib

gefitinib

ACTIVE COMPARATOR

gefitinib once daily

Drug: gefitinib

Interventions

Afatinib DRUG

afatinib once daily

Also known as: Giotrif® / Gilotrif®

afatinib

gefitinib DRUG

Gefitinib once daily

gefitinib

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.
• Prior treatment with epidermal growth factor receptor targeting small molecules or antibodies.
• Major surgery within 4 weeks of study randomisation.
• Active brain metastases
• Meningeal carcinomatosis.
• 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.
• Known pre-existing interstitial lung disease.
• Clinically relevant cardiovascular abnormalities as judged by the investigator.
• Cardiac left ventricular function with resting ejection fraction of less than institutional lower limit of normal.
• 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.
• Pregnancy or breast-feeding.
• Active hepatitis and/or known HIV carrier
• Any prohibited concomitant medications for therapy with afatinib or gefitinib

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (63)

Chris Obrien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

The Prince Charles Hospital

Chermside, Queensland, 4032, Australia

Location

Haematology & Oncology Clinics of Australasia (HOCA)

South Brisbane, Queensland, 4101, Australia

Location

Box Hill Hospital

Box Hill, Victoria, 3128, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

Cross Cancer Institute (University of Alberta)

Edmonton, Alberta, T6G 1Z2, Canada

Location

British Columbia Cancer Agency (BCCA) - Fraser Valley Cancer

Surrey, British Columbia, V1V 1Z2, Canada

Location

BC Cancer Agency - Vancouver

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Lakeridge Health Oshawa

Oshawa, Ontario, L1G 2B9, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Montreal General Hospital - McGill University Health Centre

Montreal, Quebec, H3G 1A4, Canada

Location

Cancer Hospital of Chinese Academy of Medical Science

Beijing, 100021, China

Location

Beijing Cancer Hospital

Beijing, 100036, China

Location

Sun Yat-Sen University Cancer Center

Guangzhou, 510060, China

Location

The Affiliated Cancer Hospital, Guangxi Medical University

Nanning, 530021, China

Location

Shanghai Chest Hospital

Shanghai, 200030, China

Location

Zhongshan Hospital Fudan University

Shanghai, 200032, China

Location

The First Hospital of Chinese Medical University

Shenyang, 110001, China

Location

CTR Oncologie du Pays Basque, Onco, Bayonne

Bayonne, 64100, France

Location

CTR François Baclesse

Caen, 14076, France

Location

HOP Intercommunal

Créteil, 94010, France

Location

HOP Michallon

La Tronche, 38700, France

Location

HOP Dupuytren 1

Limoges, 87042, France

Location

CTR Leon Berard

Lyon, 69373, France

Location

CTR René Gauducheau

Saint-Herblain, 44805, France

Location

HOP Sud-Réunion, Pneumo, Saint Pierre

St-Pierre - La Réunion, 97448, France

Location

Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitätsklinikum Essen gGmbH

Essen, 45122, Germany

Location

Klinikum Esslingen GmbH

Esslingen am Neckar, 73730, Germany

Location

Universitätsmedizin der Johannes Gutenberg-Universität Mainz

Mainz, 55131, Germany

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hospital

Shatin, Hong Kong

Location

St James's Hospital

Dublin, 8, Ireland

Location

Beaumont Hospital

Dublin, D09 Y5R3, Ireland

Location

Oslo Universitetssykehus HF, Radiumhospitalet

Oslo, N-0379, Norway

Location

National Cancer Centre

Singapore, 169610, Singapore

Location

Johns Hopkins Singapore International Medical Center

Singapore, 308433, Singapore

Location

Chungbuk National University Hospital

Cheongju-si, 361-771, South Korea

Location

Gachon University Gil Medical Center

Incheon, 405-760, South Korea

Location

Seoul National University Hospital

Seoul, 110-744, South Korea

Location

Severance Hospital

Seoul, 120-752, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Asan Medical Center

Seoul, 138-736, South Korea

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Regional Universitario de Málaga

Málaga, 29010, Spain

Location

Hospital Central de Asturias

Oviedo, 33006, Spain

Location

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

Location

Hospital Virgen del Rocío

Seville, 41013, Spain

Location

Sahlgrenska US, Göteborg

Gothenburg, 413 45, Sweden

Location

Universitetssjukhuset, Linköping

Linköping, 581 85, Sweden

Location

Skånes universitetssjukhus, Lund

Lund, 221 85, Sweden

Location

Karolinska Univ. sjukhuset

Stockholm, 171 76, Sweden

Location

Taichung Veterans General Hospital

Taichung, 407, Taiwan

Location

NCKUH

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

Taipe Veterans General Hospital

Taipei, 112, Taiwan

Location

Chang Gung Memorial Hospital(Linkou)

Taoyuan District, 333, Taiwan

Location

Aberdeen Royal Infirmary

Aberdeen, AB25 2ZN, United Kingdom

Location

Birmingham City Hospital

Birmingham, B18 7QH, United Kingdom

Location

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

Location

Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

Royal Surrey County Hospital

Guildford, GU2 7XX, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 29653820 DERIVED

• 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.

  PMID: 28426106 DERIVED

• 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.

  PMID: 27083334 DERIVED

MeSH Terms

Conditions

Lung Neoplasms

Interventions

Afatinib; Gefitinib

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boehringer Ingelheim Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2011
• First Posted: November 8, 2011
• Study Start: December 13, 2011
• Primary Completion: April 8, 2016
• Study Completion: April 12, 2019
• Last Updated: April 7, 2020
• Results First Posted: June 19, 2017

Record last verified: 2020-03

Locations

DE (3); FR (8); CN (7); KR (6); HK (2); NO (1); IE (2); SE (4); AU (7); SG (2); ES (5); GB (5); TW (5); CA (6)