BIBW 2992 and BSC Versus Placebo and BSC in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib (LUX-LUNG 1)

Carcinoma, Non-Small-Cell Lung Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00656136
• Other study ID #: 1200.23
• Secondary ID: 2007-005983-28
• Status: Completed
• Phase: Phase 3
• First received: April 4, 2008
• Last updated: December 15, 2014
• Start date: April 2008
• Est. completion date: October 2013

Study information

• Verified date: December 2014
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicines and Health Products, FAMHPCanada: Health CanadaChina: Food and Drug AdministrationFrance: AFFSAPSGermany: Ministry of HealthGreat Britain: MHRAHong Kong: Department of HealthItaly: Comitato Etico Azienda USL 4 - PRATOKorea, Republic of: Korea Food and Drug AdministrationNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Singapore: Health Sciences Authority, Ministry of HealthSpain: Spanish Agency for Medicines and Health ProductsTaiwan: Department of Health, Executive Yuan, TaiwanThailand: Ministry of Public HealthUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 585
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• placebo
Patients receive placebo once daily
• BIBW 2992
Patients receive afatinib tablets once daily, and can reduce dose for adverse event management. Afatinib is given once daily, continuously until disease progression or unacceptable toxicity.

Locations

Country	Name	City	State
Belgium	1200.23.32004 Boehringer Ingelheim Investigational Site	Edegem
Belgium	1200.23.32003 Boehringer Ingelheim Investigational Site	Gent
Belgium	1200.23.32001 Boehringer Ingelheim Investigational Site	Leuven
Belgium	1200.23.32005 Boehringer Ingelheim Investigational Site	Liège
Belgium	1200.23.32006 Boehringer Ingelheim Investigational Site	Namur
Canada	1200.23.1002 Boehringer Ingelheim Investigational Site	Edmonton	Alberta
Canada	1200.23.1001 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1200.23.1004 Boehringer Ingelheim Investigational Site	Montreal	Quebec
Canada	1200.23.1009 Boehringer Ingelheim Investigational Site	Toronto	Ontario
Canada	1200.23.1005 Boehringer Ingelheim Investigational Site	Vancouver	British Columbia
China	1200.23.86001 Boehringer Ingelheim Investigational Site	Beijing
China	1200.23.86002 Boehringer Ingelheim Investigational Site	Beijing
China	1200.23.86003 Boehringer Ingelheim Investigational Site	Beijing
China	1200.23.86009 Boehringer Ingelheim Investigational Site	Chengdu
China	1200.23.86007 Boehringer Ingelheim Investigational Site	Guangzhou
China	1200.23.86008 Boehringer Ingelheim Investigational Site	Hangzhou
China	1200.23.86004 Boehringer Ingelheim Investigational Site	Shanghai
China	1200.23.86005 Boehringer Ingelheim Investigational Site	Shanghai
China	1200.23.86006 Boehringer Ingelheim Investigational Site	Shanghai
France	1200.23.3303A Boehringer Ingelheim Investigational Site	Besançon Cedex
France	1200.23.3303C Boehringer Ingelheim Investigational Site	Besançon Cedex
France	1200.23.3305A Boehringer Ingelheim Investigational Site	Caen Cedex 5
France	1200.23.3304A Boehringer Ingelheim Investigational Site	La Tronche
France	1200.23.3304B Boehringer Ingelheim Investigational Site	La Tronche
France	1200.23.3307A Boehringer Ingelheim Investigational Site	Lyon Cedex 4
France	1200.23.3302A Boehringer Ingelheim Investigational Site	Paris
France	1200.23.3302B Boehringer Ingelheim Investigational Site	Paris
France	1200.23.3301A Boehringer Ingelheim Investigational Site	Paris cedex 20
France	1200.23.3306A Boehringer Ingelheim Investigational Site	Toulouse cedex 9
France	1200.23.3306C Boehringer Ingelheim Investigational Site	Toulouse cedex 9
Germany	1200.23.49010 Zentralklinik Bad Berka GmbH	Bad Berka
Germany	1200.23.49002 Innere Klinik und Poliklinik (Tumorforschung)	Essen
Germany	1200.23.49003 Asklepios Fachkliniken München-Gauting	Gauting
Germany	1200.23.49005 Krankenhaus Großhansdorf	Großhansdorf
Germany	1200.23.49008 Universitätsklinik Hamburg-Eppendorf	Hamburg
Germany	1200.23.49004 Johannes Gutenberg-Universität Mainz	Mainz
Germany	1200.23.49001 Universitätsklinikum Mannheim	Mannheim
Germany	1200.23.49006 HSK, Dr. Horst-Schmidt-Kliniken GmbH	Wiesbaden
Hong Kong	1200.23.85202 Boehringer Ingelheim Investigational Site	Hong Kong
Italy	1200.23.39003 Boehringer Ingelheim Investigational Site	Genova
Italy	1200.23.39007 Boehringer Ingelheim Investigational Site	Orbassano (TO)
Italy	1200.23.39002 Boehringer Ingelheim Investigational Site	Perugia
Italy	1200.23.39004 Boehringer Ingelheim Investigational Site	Prato
Italy	1200.23.39008 Boehringer Ingelheim Investigational Site	Roma
Italy	1200.23.39001 Boehringer Ingelheim Investigational Site	Rozzano (MI)
Korea, Republic of	1200.23.82005 Boehringer Ingelheim Investigational Site	Gyeonggi-do
Korea, Republic of	1200.23.82006 Boehringer Ingelheim Investigational Site	Hwasun
Korea, Republic of	1200.23.82001 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1200.23.82002 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1200.23.82003 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1200.23.82004 Boehringer Ingelheim Investigational Site	Seoul
Netherlands	1200.23.31002 Boehringer Ingelheim Investigational Site	Amsterdam
Netherlands	1200.23.31001 Boehringer Ingelheim Investigational Site	Groningen
Netherlands	1200.23.31003 Boehringer Ingelheim Investigational Site	Helmond
Singapore	1200.23.65001 Boehringer Ingelheim Investigational Site	Singapore
Spain	1200.23.3405 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1200.23.3404 Boehringer Ingelheim Investigational Site	Cruces
Spain	1200.23.3401 Boehringer Ingelheim Investigational Site	Madrid
Spain	1200.23.3403 Boehringer Ingelheim Investigational Site	Madrid
Spain	1200.23.3406 Boehringer Ingelheim Investigational Site	Madrid
Spain	1200.23.3402 Boehringer Ingelheim Investigational Site	Valencia
Taiwan	1200.23.88604 Taichung Veterans General Hospital	Taichung
Taiwan	1200.23.88605 China Medical University Hospital	Taichung
Taiwan	1200.23.88606 National Cheng Kung University Hospital	Tainan
Taiwan	1200.23.88601 National Taiwan University Hospital	Taipei
Taiwan	1200.23.88602 Veterans General Hospital	Taipei
Taiwan	1200.23.88607 Tri-Service General Hospital	Taipei
Taiwan	1200.23.88603 Chang Gung Memorial Hosp-Linkou	Taoyuan
Thailand	1200.23.66001 Boehringer Ingelheim Investigational Site	Chiangmai
Thailand	1200.23.66003 Boehringer Ingelheim Investigational Site	Pathumwan, Bangkok
Thailand	1200.23.66002 Boehringer Ingelheim Investigational Site	Songkla
United Kingdom	1200.23.4404 Boehringer Ingelheim Investigational Site	Dundee
United Kingdom	1200.23.4403 Boehringer Ingelheim Investigational Site	Edinburgh
United Kingdom	1200.23.4401 Boehringer Ingelheim Investigational Site	Glasgow
United Kingdom	1200.23.4405 Boehringer Ingelheim Investigational Site	London
United Kingdom	1200.23.4406 Boehringer Ingelheim Investigational Site	Sutton
United States	1200.23.027 Boehringer Ingelheim Investigational Site	Anaheim	California
United States	1200.23.028 Boehringer Ingelheim Investigational Site	Berkeley	California
United States	1200.23.046 Boehringer Ingelheim Investigational Site	Fayetteville	Arkansas
United States	1200.23.038 Boehringer Ingelheim Investigational Site	Kingman	Arizona
United States	1200.23.029 Boehringer Ingelheim Investigational Site	Modesto	California
United States	1200.23.045 Boehringer Ingelheim Investigational Site	Montebello	California
United States	1200.23.020 Boehringer Ingelheim Investigational Site	New York	New York
United States	1200.23.024 Boehringer Ingelheim Investigational Site	North Miami Beach	Florida
United States	1200.23.009 Boehringer Ingelheim Investigational Site	Orange	California
United States	1200.23.026 Boehringer Ingelheim Investigational Site	Palm Springs	California
United States	1200.23.039 Boehringer Ingelheim Investigational Site	Renton	Washington
United States	1200.23.056 Boehringer Ingelheim Investigational Site	Salt lake City	Utah
United States	1200.23.050 Boehringer Ingelheim Investigational Site	Seattle	Washington
United States	1200.23.013 Boehringer Ingelheim Investigational Site	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  China,  France,  Germany,  Hong Kong,  Italy,  Korea, Republic of,  Netherlands,  Singapore,  Spain,  Taiwan,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Overall survival was the duration from the date of randomization to the date of death. Patients who were alive were censored at the last contact date prior to the database lock.; For the primary analysis 11 patients were lost to follow-up and were censored at the last contact date when they were known to be still alive. Primary analysis data cut-off date was 08 July 2010.; For the final analysis 13 patients were lost to follow-up and were censored at the last contact date when they were known to be still alive. Final analysis data cut-off date was 04 October 2013.	From randomization until death or the last patient out date, an average of 12 months	No
Secondary	Progression-free Survival (PFS)	PFS is defined as time from randomisation to disease progression or death whichever occurs first. Assessed by central independent review according to the Response Evaluation Criteria in Solid Tumours version 1.0 (RECIST 1.0).	From randomization to disease progression, death or the data cutoff on 07 July 2010, an average of 3.3 months	No
Secondary	Objective Response Rate (OR)	OR is defined as complete response (CR) and partial response (PR). Assessed by central independent review according to RECIST 1.0.	From randomization to disease progression, death or the data cutoff on 07 July 2010, an average of 3.3 months	No

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