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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00949650




Registration number
NCT00949650
Ethics application status
Date submitted
29/07/2009
Date registered
30/07/2009
Date last updated
6/04/2018

Titles & IDs
Public title
BIBW 2992 (Afatinib) Versus Chemotherapy as First Line Treatment in NSCLC With EGFR Mutation
Scientific title
A Randomised, Open-label, Phase III Study of BIBW 2992 Versus Chemotherapy as First-line Treatment for Patients With Stage IIIB or IV Adenocarcinoma of the Lung Harbouring an EGFR Activating Mutation
Secondary ID [1] 0 0
2008-005615-18
Secondary ID [2] 0 0
1200.32
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Carcinoma, Non-Small-Cell Lung 0 0
Adenocarcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Non small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pemetrexed
Treatment: Drugs - BIBW 2992
Treatment: Drugs - Cisplatin

Experimental: BIBW 2992 - BIBW 2992 tablet once daily until progression

Active comparator: Cisplatin/Pemetrexed - Cisplatin and Pemetrexed IV once every 3 weeks for up to 6 cycles


Treatment: Drugs: Pemetrexed
Pemetrexed IV given once every 3 weeks for up to 6 cycles

Treatment: Drugs: BIBW 2992
BIBW 2992 once daily until progression

Treatment: Drugs: Cisplatin
Cisplatin IV given once every 3 weeks for up to 6 cycles
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) Time
Timepoint [1] 0 0
Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Secondary outcome [1] 0 0
Percentage of Patients With Objective Response (OR)
Timepoint [1] 0 0
Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Secondary outcome [2] 0 0
Percentage of Participants With Disease Control (DC)
Timepoint [2] 0 0
Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Secondary outcome [3] 0 0
Overall Survival (OS) Time
Timepoint [3] 0 0
From randomisation to cut-off date (17MAR2017).
Secondary outcome [4] 0 0
Tumour Shrinkage
Timepoint [4] 0 0
Tumour assessments were performed at Screening, Week 6, Week 12, Week 18 and then every 12-18 weeks until disease progression
Secondary outcome [5] 0 0
Change From Baseline in Body Weight
Timepoint [5] 0 0
Baseline and throughout the trial until progression (every 3 weeks), up to 28 months.
Secondary outcome [6] 0 0
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)
Timepoint [6] 0 0
Throughout the trial until progression (every 3 weeks), up to 28 months.
Secondary outcome [7] 0 0
Health Related Quality of Life (HRQOL): Time to Deterioration in Coughing
Timepoint [7] 0 0
Throughout the trial until progression (every 3 weeks).
Secondary outcome [8] 0 0
HRQOL: Time to Deterioration in Dyspnoea
Timepoint [8] 0 0
Throughout the trial until progression (every 3 weeks).
Secondary outcome [9] 0 0
HRQOL: Time to Deterioration in Pain
Timepoint [9] 0 0
Throughout the trial until progression (every 3 weeks).
Secondary outcome [10] 0 0
Trough Plasma Concentrations of Afatinib at Day 22
Timepoint [10] 0 0
Day 22.
Secondary outcome [11] 0 0
Trough Plasma Concentrations of Afatinib at Day 29
Timepoint [11] 0 0
Day 29.
Secondary outcome [12] 0 0
Trough Plasma Concentrations of Afatinib at Day 43
Timepoint [12] 0 0
Day 43.

Eligibility
Key inclusion criteria
Inclusion criteria:

* Pathologically confirmed diagnosis of Stage IIIB (with cytologically proven pleural effusion or pericardial effusion) or Stage IV adenocarcinoma of the lung. Patients with mixed histology are eligible if adenocarcinoma is the predominant histology.
* Epidermal Growth Factor Receptor mutation detected by central laboratory analysis of tumour biopsy material.
* Measurable disease according to RECIST 1.1.
* Eastern Cooperative Oncology Group score of 0 or 1.
* Age >/= 18 years.
* Life expectancy of at least three months.
* Written informed consent that is consistent with International Conference on Harmonisation-Good Clinical Practice guidelines.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

* Prior chemotherapy for relapsed and/or metastatic NSCLC. Neoadjuvant/adjuvant chemotherapy is permitted if at least 12 months has elapsed between the end of chemotherapy and randomisation.
* Prior treatment with Epidermal Growth Factor Receptor targeting small molecules or antibodies.
* Radiotherapy or surgery (other than biopsy) within 4 weeks prior to randomisation.
* Active brain metastases
* Any other current malignancy or malignancy diagnosed within the past five years
* Known pre-existing interstitial lung disease.
* Significant or recent acute gastrointestinal disorders with diarrhoea as a major symptom.
* History or presence of clinically relevant cardiovascular abnormalities.
* Any other concomitant serious illness or organ system dysfunction.
* Adequate absolute neutrophil count and platelet count
* Adequate liver and kidney function
* Active hepatitis B infection, active hepatitis C infection or known HIV carrier.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/08/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
16/03/2017
Sample size
Target
Accrual to date
Final
345
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Lifehouse - Camperdown
Recruitment hospital [2] 0 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 0 0
Calvary Mater Newcastle Hospital - Waratah
Recruitment hospital [4] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [5] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [6] 0 0
The Burnside War Memorial Hospital - Toorak Gardens
Recruitment hospital [7] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [8] 0 0
St. Vincents Hospital (MEL) - Fitzroy
Recruitment hospital [9] 0 0
Mount Medical Centre - Perth
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
4032 - Chermside
Recruitment postcode(s) [5] 0 0
5042 - Bedford Park
Recruitment postcode(s) [6] 0 0
5065 - Toorak Gardens
Recruitment postcode(s) [7] 0 0
3128 - Box Hill
Recruitment postcode(s) [8] 0 0
3065 - Fitzroy
Recruitment postcode(s) [9] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
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United States of America
State/province [2] 0 0
California
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United States of America
State/province [3] 0 0
Florida
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United States of America
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Louisiana
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United States of America
State/province [5] 0 0
New York
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United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
Argentina
State/province [8] 0 0
Bahía Blanca
Country [9] 0 0
Argentina
State/province [9] 0 0
Capital Federal
Country [10] 0 0
Argentina
State/province [10] 0 0
Rosario
Country [11] 0 0
Austria
State/province [11] 0 0
Linz
Country [12] 0 0
Austria
State/province [12] 0 0
Wels
Country [13] 0 0
Austria
State/province [13] 0 0
Wien
Country [14] 0 0
Belgium
State/province [14] 0 0
Bruxelles
Country [15] 0 0
Belgium
State/province [15] 0 0
Gent
Country [16] 0 0
Belgium
State/province [16] 0 0
Jette
Country [17] 0 0
Belgium
State/province [17] 0 0
Leuven
Country [18] 0 0
Belgium
State/province [18] 0 0
Liège
Country [19] 0 0
Brazil
State/province [19] 0 0
Belo Horizonte
Country [20] 0 0
Brazil
State/province [20] 0 0
Cachoeiro de Itapemirim
Country [21] 0 0
Brazil
State/province [21] 0 0
Curitiba
Country [22] 0 0
Brazil
State/province [22] 0 0
Porto Alegre
Country [23] 0 0
Brazil
State/province [23] 0 0
Sao Paulo
Country [24] 0 0
Canada
State/province [24] 0 0
Alberta
Country [25] 0 0
Canada
State/province [25] 0 0
Migration Data
Country [26] 0 0
Chile
State/province [26] 0 0
Los Condes
Country [27] 0 0
Chile
State/province [27] 0 0
Reñaca
Country [28] 0 0
Chile
State/province [28] 0 0
Temuco
Country [29] 0 0
France
State/province [29] 0 0
Angers
Country [30] 0 0
France
State/province [30] 0 0
Caen Cedex 5
Country [31] 0 0
France
State/province [31] 0 0
La Tronche
Country [32] 0 0
France
State/province [32] 0 0
Lyon Cedex 4
Country [33] 0 0
France
State/province [33] 0 0
Paris Cedex 05
Country [34] 0 0
France
State/province [34] 0 0
Saint Herblain
Country [35] 0 0
France
State/province [35] 0 0
Saint Pierre - La Réunion
Country [36] 0 0
France
State/province [36] 0 0
Toulon
Country [37] 0 0
France
State/province [37] 0 0
Villefranche Sur Saône
Country [38] 0 0
Germany
State/province [38] 0 0
Berlin
Country [39] 0 0
Germany
State/province [39] 0 0
Essen
Country [40] 0 0
Germany
State/province [40] 0 0
Hannover
Country [41] 0 0
Germany
State/province [41] 0 0
Hemer
Country [42] 0 0
Germany
State/province [42] 0 0
Mainz
Country [43] 0 0
Germany
State/province [43] 0 0
Münster
Country [44] 0 0
Germany
State/province [44] 0 0
Oldenburg
Country [45] 0 0
Germany
State/province [45] 0 0
Taipei
Country [46] 0 0
Hong Kong
State/province [46] 0 0
Hong Kong
Country [47] 0 0
Hong Kong
State/province [47] 0 0
Shatin
Country [48] 0 0
Hungary
State/province [48] 0 0
Szekesfehervar
Country [49] 0 0
Hungary
State/province [49] 0 0
Szombathely
Country [50] 0 0
Hungary
State/province [50] 0 0
Zalaegerszeg
Country [51] 0 0
Ireland
State/province [51] 0 0
Dublin 8
Country [52] 0 0
Italy
State/province [52] 0 0
Arezzo
Country [53] 0 0
Italy
State/province [53] 0 0
Prato
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Italy
State/province [54] 0 0
Roma
Country [55] 0 0
Italy
State/province [55] 0 0
Sant'Andrea Delle Fratte (PG)
Country [56] 0 0
Japan
State/province [56] 0 0
Aichi, Nagoya
Country [57] 0 0
Japan
State/province [57] 0 0
Chiba, Kashiwa
Country [58] 0 0
Japan
State/province [58] 0 0
Ehime, Matsuyama
Country [59] 0 0
Japan
State/province [59] 0 0
Fukuoka, Fukuoka
Country [60] 0 0
Japan
State/province [60] 0 0
Hokkaido, Sapporo
Country [61] 0 0
Japan
State/province [61] 0 0
Hyogo, Kobe
Country [62] 0 0
Japan
State/province [62] 0 0
Ishikawa, Kanazawa
Country [63] 0 0
Japan
State/province [63] 0 0
Kanagawa, Yokohama
Country [64] 0 0
Japan
State/province [64] 0 0
Niigata, Niigata
Country [65] 0 0
Japan
State/province [65] 0 0
Okayama, Kurashiki
Country [66] 0 0
Japan
State/province [66] 0 0
Okayama, Okayama
Country [67] 0 0
Japan
State/province [67] 0 0
Osaka, Osaka-Sayama
Country [68] 0 0
Japan
State/province [68] 0 0
Osaka, Osaka
Country [69] 0 0
Japan
State/province [69] 0 0
Sakai, Osaka
Country [70] 0 0
Japan
State/province [70] 0 0
Shizuoka, Sunto-gun
Country [71] 0 0
Korea, Republic of
State/province [71] 0 0
Cheongju
Country [72] 0 0
Korea, Republic of
State/province [72] 0 0
Hwasun
Country [73] 0 0
Korea, Republic of
State/province [73] 0 0
Seongnam
Country [74] 0 0
Korea, Republic of
State/province [74] 0 0
Seoul
Country [75] 0 0
Korea, Republic of
State/province [75] 0 0
Ulsan
Country [76] 0 0
Malaysia
State/province [76] 0 0
Palau Pinang
Country [77] 0 0
Malaysia
State/province [77] 0 0
Wilayah Persekutuan
Country [78] 0 0
Peru
State/province [78] 0 0
La Victoria
Country [79] 0 0
Peru
State/province [79] 0 0
San Isidro
Country [80] 0 0
Peru
State/province [80] 0 0
Surquillo
Country [81] 0 0
Philippines
State/province [81] 0 0
Cebu City
Country [82] 0 0
Philippines
State/province [82] 0 0
Makati City
Country [83] 0 0
Philippines
State/province [83] 0 0
Quezon
Country [84] 0 0
Romania
State/province [84] 0 0
Cluj Napoca
Country [85] 0 0
Romania
State/province [85] 0 0
Craiova
Country [86] 0 0
Russian Federation
State/province [86] 0 0
Kazan
Country [87] 0 0
Russian Federation
State/province [87] 0 0
Moscow
Country [88] 0 0
Russian Federation
State/province [88] 0 0
Obninsk
Country [89] 0 0
Russian Federation
State/province [89] 0 0
St. Petersburg
Country [90] 0 0
Taiwan
State/province [90] 0 0
Kaohsiung
Country [91] 0 0
Taiwan
State/province [91] 0 0
Taichung
Country [92] 0 0
Taiwan
State/province [92] 0 0
Tainan
Country [93] 0 0
Taiwan
State/province [93] 0 0
Taipei
Country [94] 0 0
Taiwan
State/province [94] 0 0
Taoyuan
Country [95] 0 0
Thailand
State/province [95] 0 0
Bangkok
Country [96] 0 0
Thailand
State/province [96] 0 0
Chiang Mai
Country [97] 0 0
Thailand
State/province [97] 0 0
Khonkaen
Country [98] 0 0
Thailand
State/province [98] 0 0
Songkla
Country [99] 0 0
Ukraine
State/province [99] 0 0
Dnipropetrovsk
Country [100] 0 0
Ukraine
State/province [100] 0 0
Donetsk
Country [101] 0 0
Ukraine
State/province [101] 0 0
Kharkiv
Country [102] 0 0
Ukraine
State/province [102] 0 0
Lviv
Country [103] 0 0
United Kingdom
State/province [103] 0 0
Exeter
Country [104] 0 0
United Kingdom
State/province [104] 0 0
Guildford
Country [105] 0 0
United Kingdom
State/province [105] 0 0
London
Country [106] 0 0
United Kingdom
State/province [106] 0 0
Maidstone
Country [107] 0 0
United Kingdom
State/province [107] 0 0
Scunthorpe
Country [108] 0 0
United Kingdom
State/province [108] 0 0
Sutton
Country [109] 0 0
United Kingdom
State/province [109] 0 0
Truro

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Boehringer Ingelheim
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This randomised, open label phase III trial will be performed in patients with adenocarcinoma of the lung with tumours harbouring an Epidermal Growth Factor Receptor activating mutation. The objectives of the trial are to compare the efficacy of single agent BIBW 2992, Arm A, with Pemetrexed/Cisplatin chemotherapy, Arm B, as first line treatment for this group of patients.
Trial website
https://clinicaltrials.gov/study/NCT00949650
Trial related presentations / publications
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.
Yang JC, Sequist LV, Zhou C, Schuler M, Geater SL, Mok T, Hu CP, Yamamoto N, Feng J, O'Byrne K, Lu S, Hirsh V, Huang Y, Sebastian M, Okamoto I, Dickgreber N, Shah R, Marten A, Massey D, Wind S, Wu YL. Effect of dose adjustment on the safety and efficacy of afatinib for EGFR mutation-positive lung adenocarcinoma: post hoc analyses of the randomized LUX-Lung 3 and 6 trials. Ann Oncol. 2016 Nov;27(11):2103-2110. doi: 10.1093/annonc/mdw322. Epub 2016 Sep 6.
Schuler M, Wu YL, Hirsh V, O'Byrne K, Yamamoto N, Mok T, Popat S, Sequist LV, Massey D, Zazulina V, Yang JC. First-Line Afatinib versus Chemotherapy in Patients with Non-Small Cell Lung Cancer and Common Epidermal Growth Factor Receptor Gene Mutations and Brain Metastases. J Thorac Oncol. 2016 Mar;11(3):380-90. doi: 10.1016/j.jtho.2015.11.014. Epub 2016 Jan 25.
Kato T, Yoshioka H, Okamoto I, Yokoyama A, Hida T, Seto T, Kiura K, Massey D, Seki Y, Yamamoto N. Afatinib versus cisplatin plus pemetrexed in Japanese patients with advanced non-small cell lung cancer harboring activating EGFR mutations: Subgroup analysis of LUX-Lung 3. Cancer Sci. 2015 Sep;106(9):1202-11. doi: 10.1111/cas.12723. Epub 2015 Jul 25.
Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. doi: 10.1016/S1470-2045(15)00026-1. Epub 2015 Jun 4.
Yang JC, Wu YL, Schuler M, Sebastian M, Popat S, Yamamoto N, Zhou C, Hu CP, O'Byrne K, Feng J, Lu S, Huang Y, Geater SL, Lee KY, Tsai CM, Gorbunova V, Hirsh V, Bennouna J, Orlov S, Mok T, Boyer M, Su WC, Lee KH, Kato T, Massey D, Shahidi M, Zazulina V, Sequist LV. Afatinib versus cisplatin-based chemotherapy for EGFR mutation-positive lung adenocarcinoma (LUX-Lung 3 and LUX-Lung 6): analysis of overall survival data from two randomised, phase 3 trials. Lancet Oncol. 2015 Feb;16(2):141-51. doi: 10.1016/S1470-2045(14)71173-8. Epub 2015 Jan 12.
Yang JC, Hirsh V, Schuler M, Yamamoto N, O'Byrne KJ, Mok TS, Zazulina V, Shahidi M, Lungershausen J, Massey D, Palmer M, Sequist LV. Symptom control and quality of life in LUX-Lung 3: a phase III study of afatinib or cisplatin/pemetrexed in patients with advanced lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3342-50. doi: 10.1200/JCO.2012.46.1764. Epub 2013 Jul 1.
Sequist LV, Yang JC, Yamamoto N, O'Byrne K, Hirsh V, Mok T, Geater SL, Orlov S, Tsai CM, Boyer M, Su WC, Bennouna J, Kato T, Gorbunova V, Lee KH, Shah R, Massey D, Zazulina V, Shahidi M, Schuler M. Phase III study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations. J Clin Oncol. 2013 Sep 20;31(27):3327-34. doi: 10.1200/JCO.2012.44.2806. Epub 2013 Jul 1.
Public notes

Contacts
Principal investigator
Name 0 0
Boehringer Ingelheim
Address 0 0
Boehringer Ingelheim
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00949650