Clinical trial NCT00656136: BIBW 2992 and BSC Versus Placebo and BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-LUNG 1)
Official title: Phase IIb/III Randomized, Double-blind Trial of BIBW 2992 Plus Best Supportive Care (BSC) Versus Placebo Plus BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-Lung 1)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2008-04-10
Enrollment: 585
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 randomized, double-blind, multi-center Phase IIb/III trial will be performed in patients with NSCLC who have received previous treatment with at least one but not more than two lines of cytotoxic chemotherapy (one line must have been a platinum-containing regimen) and either gefitinib or erlotinib for a period of at least 12 weeks and then progressed.

The primary objective of this randomized trial is to determine the efficacy of BIBW 2992 as a single agent (Arm A) as compared to a matching placebo (Arm B) in this patient population. Patients on both treatment arms will receive best supportive care in addition to study treatment.

Patients enrolled into the trial will be treated and followed until death or lost to follow-up.


Eligibility criteria: Inclusion criteria:

1. Patients with pathologic confirmation of NSCLC Stage III-B (with pleural effusion) or Stage IV adenocarcinoma who have failed at least one but not more than two lines of cytotoxic chemotherapy (including adjuvant chemotherapy). One of the chemotherapy regimens must have been platinum-based.
2. Progressive disease following at least 12 weeks of treatment with erlotinib (Tarceva®) or gefitinib (Iressa®)
3. Eastern Cooperative Oncology Group (ECOG, R01-0787) performance Score 0, 1 or 2
4. Patients with at least one tumor lesion that can accurately be measured by magnetic resonance imaging (MRI), or computed tomography (CT) in at least one dimension with longest diameter to be recorded as \>20 mm using conventional techniques or \>10 mm with spiral CT scan
5. Male and female patients age \>18 years
6. Life expectancy of at least three (3) months
7. Written informed consent that is consistent with ICH-GCP guidelines

Exclusion criteria:

1. Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within 14 days of treatment Day 1
2. Chemo-, hormone- (other than megestrol acetate or steroids required for maintenance non-cancer therapy) or immunotherapy within the past 4 weeks
3. Active brain metastases
4. Significant or recent acute gastrointestinal disorders with diarrhea
5. Patients who have any other life-threatening illness or organ system dysfunction,
6. Other malignancies diagnosed within the past five (5) years
7. Radiotherapy within the past 2 weeks prior to treatment
8. History of clinically significant or uncontrolled cardiac disease
9. Adequate ANC and platelet count
10. Adequate liver and kidney function
11. Patients with any serious active infection including known HIV, active hepatitis B or active hepatitis C

Primary outcomes:
measure: Overall Survival
timeFrame: From randomization until death or the last patient out date, an average of 12 months
Secondary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: From randomization to disease progression, death or the data cutoff on 07 July 2010, an average of 3.3 months
measure: Objective Response Rate (OR)
timeFrame: From randomization to disease progression, death or the data cutoff on 07 July 2010, an average of 3.3 months
Other outcomes:
Locations:
city: Kingman
country: United States
facility: 1200.23.038 Boehringer Ingelheim Investigational Site
state: Arizona
city: Fayetteville
country: United States
facility: 1200.23.046 Boehringer Ingelheim Investigational Site
state: Arkansas
city: Anaheim
country: United States
facility: 1200.23.027 Boehringer Ingelheim Investigational Site
state: California
city: Berkeley
country: United States
facility: 1200.23.028 Boehringer Ingelheim Investigational Site
state: California
city: Modesto
country: United States
facility: 1200.23.029 Boehringer Ingelheim Investigational Site
state: California
city: Montebello
country: United States
facility: 1200.23.045 Boehringer Ingelheim Investigational Site
state: California
city: Orange
country: United States
facility: 1200.23.009 Boehringer Ingelheim Investigational Site
state: California
city: Palm Springs
country: United States
facility: 1200.23.026 Boehringer Ingelheim Investigational Site
state: California
city: North Miami Beach
country: United States
facility: 1200.23.024 Boehringer Ingelheim Investigational Site
state: Florida
city: New York
country: United States
facility: 1200.23.020 Boehringer Ingelheim Investigational Site
state: New York
city: Valhalla
country: United States
facility: 1200.23.013 Boehringer Ingelheim Investigational Site
state: New York
city: Salt lake City
country: United States
facility: 1200.23.056 Boehringer Ingelheim Investigational Site
state: Utah
city: Renton
country: United States
facility: 1200.23.039 Boehringer Ingelheim Investigational Site
state: Washington
city: Seattle
country: United States
facility: 1200.23.050 Boehringer Ingelheim Investigational Site
state: Washington
city: Edegem
country: Belgium
facility: 1200.23.32004 Boehringer Ingelheim Investigational Site
city: Gent
country: Belgium
facility: 1200.23.32003 Boehringer Ingelheim Investigational Site
city: Leuven
country: Belgium
facility: 1200.23.32001 Boehringer Ingelheim Investigational Site
city: Liège
country: Belgium
facility: 1200.23.32005 Boehringer Ingelheim Investigational Site
city: Namur
country: Belgium
facility: 1200.23.32006 Boehringer Ingelheim Investigational Site
city: Edmonton
country: Canada
facility: 1200.23.1002 Boehringer Ingelheim Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: 1200.23.1005 Boehringer Ingelheim Investigational Site
state: British Columbia
city: Toronto
country: Canada
facility: 1200.23.1009 Boehringer Ingelheim Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: 1200.23.1001 Boehringer Ingelheim Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: 1200.23.1004 Boehringer Ingelheim Investigational Site
state: Quebec
city: Beijing
country: China
facility: 1200.23.86001 Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: 1200.23.86002 Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: 1200.23.86003 Boehringer Ingelheim Investigational Site
city: Chengdu
country: China
facility: 1200.23.86009 Boehringer Ingelheim Investigational Site
city: Guangzhou
country: China
facility: 1200.23.86007 Boehringer Ingelheim Investigational Site
city: Hangzhou
country: China
facility: 1200.23.86008 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1200.23.86004 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1200.23.86005 Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: 1200.23.86006 Boehringer Ingelheim Investigational Site
city: Besançon Cedex
country: France
facility: 1200.23.3303A Boehringer Ingelheim Investigational Site
city: Besançon Cedex
country: France
facility: 1200.23.3303C Boehringer Ingelheim Investigational Site
city: Caen Cedex 5
country: France
facility: 1200.23.3305A Boehringer Ingelheim Investigational Site
city: La Tronche
country: France
facility: 1200.23.3304A Boehringer Ingelheim Investigational Site
city: La Tronche
country: France
facility: 1200.23.3304B Boehringer Ingelheim Investigational Site
city: Lyon Cedex 4
country: France
facility: 1200.23.3307A Boehringer Ingelheim Investigational Site
city: Paris cedex 20
country: France
facility: 1200.23.3301A Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1200.23.3302A Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: 1200.23.3302B Boehringer Ingelheim Investigational Site
city: Toulouse cedex 9
country: France
facility: 1200.23.3306A Boehringer Ingelheim Investigational Site
city: Toulouse cedex 9
country: France
facility: 1200.23.3306C Boehringer Ingelheim Investigational Site
city: Bad Berka
country: Germany
facility: 1200.23.49010 Zentralklinik Bad Berka GmbH
city: Essen
country: Germany
facility: 1200.23.49002 Innere Klinik und Poliklinik (Tumorforschung)
city: Gauting
country: Germany
facility: 1200.23.49003 Asklepios Fachkliniken München-Gauting
city: Großhansdorf
country: Germany
facility: 1200.23.49005 Krankenhaus Großhansdorf
city: Hamburg
country: Germany
facility: 1200.23.49008 Universitätsklinik Hamburg-Eppendorf
city: Mainz
country: Germany
facility: 1200.23.49004 Johannes Gutenberg-Universität Mainz
city: Mannheim
country: Germany
facility: 1200.23.49001 Universitätsklinikum Mannheim
city: Wiesbaden
country: Germany
facility: 1200.23.49006 HSK, Dr. Horst-Schmidt-Kliniken GmbH
city: Hong Kong
country: Hong Kong
facility: 1200.23.85202 Boehringer Ingelheim Investigational Site
city: Genova
country: Italy
facility: 1200.23.39003 Boehringer Ingelheim Investigational Site
city: Orbassano (TO)
country: Italy
facility: 1200.23.39007 Boehringer Ingelheim Investigational Site
city: Perugia
country: Italy
facility: 1200.23.39002 Boehringer Ingelheim Investigational Site
city: Prato
country: Italy
facility: 1200.23.39004 Boehringer Ingelheim Investigational Site
city: Roma
country: Italy
facility: 1200.23.39008 Boehringer Ingelheim Investigational Site
city: Rozzano (MI)
country: Italy
facility: 1200.23.39001 Boehringer Ingelheim Investigational Site
city: Gyeonggi-do
country: Korea, Republic of
facility: 1200.23.82005 Boehringer Ingelheim Investigational Site
city: Hwasun
country: Korea, Republic of
facility: 1200.23.82006 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1200.23.82001 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1200.23.82002 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1200.23.82003 Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: 1200.23.82004 Boehringer Ingelheim Investigational Site
city: Amsterdam
country: Netherlands
facility: 1200.23.31002 Boehringer Ingelheim Investigational Site
city: Groningen
country: Netherlands
facility: 1200.23.31001 Boehringer Ingelheim Investigational Site
city: Helmond
country: Netherlands
facility: 1200.23.31003 Boehringer Ingelheim Investigational Site
city: Singapore
country: Singapore
facility: 1200.23.65001 Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: 1200.23.3405 Boehringer Ingelheim Investigational Site
city: Cruces
country: Spain
facility: 1200.23.3404 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1200.23.3401 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1200.23.3403 Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: 1200.23.3406 Boehringer Ingelheim Investigational Site
city: Valencia
country: Spain
facility: 1200.23.3402 Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: 1200.23.88604 Taichung Veterans General Hospital
city: Taichung
country: Taiwan
facility: 1200.23.88605 China Medical University Hospital
city: Tainan
country: Taiwan
facility: 1200.23.88606 National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: 1200.23.88601 National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: 1200.23.88602 Veterans General Hospital
city: Taipei
country: Taiwan
facility: 1200.23.88607 Tri-Service General Hospital
city: Taoyuan
country: Taiwan
facility: 1200.23.88603 Chang Gung Memorial Hosp-Linkou
city: Chiangmai
country: Thailand
facility: 1200.23.66001 Boehringer Ingelheim Investigational Site
city: Pathumwan, Bangkok
country: Thailand
facility: 1200.23.66003 Boehringer Ingelheim Investigational Site
city: Songkla
country: Thailand
facility: 1200.23.66002 Boehringer Ingelheim Investigational Site
city: Dundee
country: United Kingdom
facility: 1200.23.4404 Boehringer Ingelheim Investigational Site
city: Edinburgh
country: United Kingdom
facility: 1200.23.4403 Boehringer Ingelheim Investigational Site
city: Glasgow
country: United Kingdom
facility: 1200.23.4401 Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: 1200.23.4405 Boehringer Ingelheim Investigational Site
city: Sutton
country: United Kingdom
facility: 1200.23.4406 Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Miller VA, Hirsh V, Cadranel J, Chen YM, Park K, Kim SW, Zhou C, Su WC, Wang M, Sun Y, Heo DS, Crino L, Tan EH, Chao TY, Shahidi M, Cong XJ, Lorence RM, Yang JC. Afatinib versus placebo for patients with advanced, metastatic non-small-cell lung cancer after failure of erlotinib, gefitinib, or both, and one or two lines of chemotherapy (LUX-Lung 1): a phase 2b/3 randomised trial. Lancet Oncol. 2012 May;13(5):528-38. doi: 10.1016/S1470-2045(12)70087-6. Epub 2012 Mar 26.