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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01085136




Registration number
NCT01085136
Ethics application status
Date submitted
10/03/2010
Date registered
11/03/2010
Date last updated
4/04/2017

Titles & IDs
Public title
LUX-Lung 5: Afatinib Plus Weekly Paclitaxel Versus Investigator's Choice of Single Agent Chemotherapy Following Afatinib Monotherapy in Non-small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib
Scientific title
Phase III Randomized Trial of BIBW 2992 Plus Weekly Paclitaxel Versus Investigator's Choice of Chemotherapy Following BIBW 2992 Monotherapy in Non-small Cell Lung Cancer Patients Failing Previous Erlotinib or Gefitinib Treatment (LUX Lung 5)
Secondary ID [1] 0 0
2009-014563-39
Secondary ID [2] 0 0
1200.42
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
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 - Investigator´s choice of chemotherapy
Treatment: Drugs - BIBW 2992

Active Comparator: Investigator`s choice of chemotherapy - Patients will be treated with investigator`s choice of chemotherapy

Experimental: BIBW 2992 and Paclitaxel - Patients will be treated with BIBW 2992daily with a medium dose and weekly administration of Paclitaxel at a dose of 80 mg/m2


Treatment: Drugs: Investigator´s choice of chemotherapy
BIBW 2992 in a medium dose in combination with Paclitaxel to explore safety and efficacy versus investigator´s choice of chemotherapy

Treatment: Drugs: BIBW 2992
BIBW 2992 will be given in a medium dose in combination with Paclitaxel to explore safety and efficacy versus investigator´s choice of chemotherapy

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (Part B) - Progression free survival (PFS) time as determined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 from day of randomization until disease progression or death for patients randomised to combination therapy with afatinib plus paclitaxel or to investigator's choice of chemotherapy.
Median was calculated from the Kaplan-Meier curve.
Timepoint [1] 0 0
From randomization until disease progression or death; Up to 32 months
Secondary outcome [1] 0 0
Progression Free Survival (Part A) - Progression free survival (PFS) as determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for Part A.
Median was calculated from the Kaplan-Meier curve.
Timepoint [1] 0 0
From first dose administration until disease progression or death; Up to 51 months
Secondary outcome [2] 0 0
Overall Survival (Part B) - Overall survival (OS) as determined by the time from randomization to death in part B.
Median was calculated from the Kaplan-Meier curve.
Timepoint [2] 0 0
From randomization until death; Up to 32 months
Secondary outcome [3] 0 0
Objective Response (Part A) - Objective response defined as the best overall response of complete response [CR]: disappearance of all target lesion & partial response [PR]: =30% decrease in the sum of the longest diameter of target lesions , taking as reference the baseline sum longest diameter of Afatinib monotherapy according to RECIST 1.1 for Part A.
Timepoint [3] 0 0
Post baseline tumour-imaging was performed at every 6 weeks thereafter until disease progression; upto 51 months
Secondary outcome [4] 0 0
Objective Response (Part B) - Objective response (CR, PR) of Afatinib/paclitaxel combination therapy and comparator chemotherapy in Part B after progression in Part A according to RECIST 1.1 .
Timepoint [4] 0 0
Post baseline tumour-imaging was performed at every 8 weeks thereafter until disease progression; up to 32 Months
Secondary outcome [5] 0 0
Intensity and Incidence of Adverse Events (AEs) for Part A & Part B. - Safety of Afatinib as indicated by intensity and incidence of adverse events, graded according to United States National Cancer Institute Common terminology Criteria for Adverse Events (US NCI CTCAE) Version 3.0 both for Part A and Part B. The CTCAE grades are: 1 (mild AE), 2 (moderate AE), 3 (severe AE), 4 (life-threatening or disabling AE), 5 (death related to AE).
Timepoint [5] 0 0
From first administration of treatment until 28 days after last drug administration, up to 51 Months (Part A) and from randomization until 28 days after last drug administration of Trial medication, up to 32 Months (Part B)

Eligibility
Key inclusion criteria
Inclusion criteria:

Part A

1. Patients with pathologically confirmed diagnosis of NSCLC Stage IIIB (with
cytologically proven pleural effusion or pericardial effusion) or Stage IV who have
failed treatment with erlotinib (Tarceva) or gefitinib (Iressa).

2. Patients should have received and failed at least one line of cytotoxic chemotherapy
including a platinum-based regimen in patients eligible for platinum-based therapy and
pemetrexed in pemetrexed eligible patients (unless pemetrexed is not considered a
regulatory or clinical standard of care e.g. no label indication, no availability or
no coverage by 3rd party payer(s)) for advanced or metastatic disease and have
progressive disease following at least 12 weeks of treatment with erlotinib or
gefitinib

3. Patients pretreated with taxane-based chemotherapy for advanced or metastatic disease
must have experienced stable disease, partial or complete response as best response

4. Eastern Cooperative Oncology Group performance Score 0 or 1.

5. 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 10 mm but no less than double the slice thickness
according to RESIST 1.1.

6. Male and female patients no less than 18 years of age.

7. Life expectancy of at least three (3) months.

8. Written informed consent that is consistent with ICH-GCP guidelines. Part B 1)
Clinical benefit (disease stabilization or antitumor response) of 12 weeks duration in
Part A of the trial determined on the second tumour assessment.

2.) Patients should have progressed in Part A according to RECIST 1.1 3.) New informed
consent, including consent to biomarker sampling, must be signed before patients enter Part
B of the trial
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria:

1. Previous treatment with BIBW 2992

2. Chemo-, hormone- (other than megestrol acetate, steroids required for maintenance
non-cancer therapy or as premedication before chemotherapy) or immunotherapy within
the past 4 weeks; except for TKI pretreatment (2 weeks only)

3. Active/symptomatic brain metastases including leptomeningeal disease. Patients with a
history of treated brain metastasis must have a stable or normal brain MRT/CT scan at
screening and be at least 4 weeks post-radiation or surgery for brain metastasis.
Dexamethasone therapy will be allowed if administered as a stable dose for at least
one month before randomization.

4. Significant or recent acute gastrointestinal disorders with diarrhea as a major
symptom e.g., Crohn's disease, mal-absorption, or CTCAE Grade >2 diarrhea of any
etiology at baseline

5. Patients who have any other life-threatening illness or organ system dysfunction,
which in the opinion of the Investigator, would either compromise patient safety or
interfere with the evaluation of the safety of the test drug

6. Other malignancies diagnosed within the past five (5) years (other than
non-melanomatous skin cancer and in situ cervical cancer)

7. Radiotherapy within the past 2 weeks prior to treatment with the trial drug

8. History or presence of clinically relevant cardiovascular abnormalities such as
uncontrolled hypertension, congestive heart failure New york Heart Association (NYHA)
functional classification of 3, unstable angina, or poorly controlled arrhythmia.
Myocardial infarction within 6 months prior to entering the trial.

9. Cardiac left ventricular function with resting ejection fraction of less than 50%
measured by multigated blood pool imaging of the heart (MUGA scan) or echocardiogram .

10. Prior treatment with anthracyclines with a cumulative dose of doxorubicin (or
equivalent) at or greater than 400 mg/m2

11. Absolute neutrophil count (ANC) at or less than 1500 / mm3

12. Platelet count at or less than 100,000 / mm3

13. Bilirubin at or greater than 1.5 mg / dL (>26 mol / L, SI unit equivalent)

14. Aspartate amino transferase (AST) or alanine amino transferase (ALT) at or greater
than three times the upper limit of normal (if related to liver metastases at or
greater than five times the upper limit of normal)

15. Serum creatinine at or greater 1.5 times the upper normal limit or calculated/measured
creatinine clearance at or less than 45 mL/min

16. Women of child-bearing potential or men who are able to father a child unwilling to
use a medically acceptable method of contraception during the trial

17. Pregnancy or breast feeding

18. Patients unable to comply with the protocol

19. Patients with any serious active infection including known human immunodeficiency
virus (HIV), active hepatitis B or active hepatitis C

20. Known or suspected active drug or alcohol abuse

21. Pre-existing or current Interstitial lung disease (ILD) 22.)

22. Peripheral polyneuropathy of > Grade 2

23. Requirement for treatment with any of the pohibited concomitant medication listed in
section 4.2.2.1.

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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Boehringer Ingelheim Investigational Site - Kingswood
Recruitment hospital [2] 0 0
Boehringer Ingelheim Investigational Site - South Brisbane
Recruitment hospital [3] 0 0
Boehringer Ingelheim Investigational Site - Box Hill
Recruitment hospital [4] 0 0
Boehringer Ingelheim Investigational Site - Fitzroy
Recruitment hospital [5] 0 0
Boehringer Ingelheim Investigational Site - Wodonga
Recruitment postcode(s) [1] 0 0
- Kingswood
Recruitment postcode(s) [2] 0 0
- South Brisbane
Recruitment postcode(s) [3] 0 0
- Box Hill
Recruitment postcode(s) [4] 0 0
- Fitzroy
Recruitment postcode(s) [5] 0 0
- Wodonga
Recruitment outside Australia
Country [1] 0 0
Argentina
State/province [1] 0 0
Ciudad Autonoma de Buenos Aires
Country [2] 0 0
Austria
State/province [2] 0 0
Salzburg
Country [3] 0 0
Belgium
State/province [3] 0 0
Aalst
Country [4] 0 0
Belgium
State/province [4] 0 0
Bruxelles
Country [5] 0 0
Belgium
State/province [5] 0 0
Duffel
Country [6] 0 0
Belgium
State/province [6] 0 0
La Louvière
Country [7] 0 0
Belgium
State/province [7] 0 0
Liège
Country [8] 0 0
Belgium
State/province [8] 0 0
Middelheim
Country [9] 0 0
Belgium
State/province [9] 0 0
Ottignies
Country [10] 0 0
Brazil
State/province [10] 0 0
Porto Alegre
Country [11] 0 0
China
State/province [11] 0 0
Beijing
Country [12] 0 0
China
State/province [12] 0 0
Changchun
Country [13] 0 0
China
State/province [13] 0 0
Chengdu
Country [14] 0 0
China
State/province [14] 0 0
Fuzhou
Country [15] 0 0
China
State/province [15] 0 0
Guangzhou
Country [16] 0 0
China
State/province [16] 0 0
Hangzhou
Country [17] 0 0
China
State/province [17] 0 0
Nanjing
Country [18] 0 0
China
State/province [18] 0 0
Shanghai
Country [19] 0 0
Finland
State/province [19] 0 0
Helsinki
Country [20] 0 0
France
State/province [20] 0 0
Bayonne
Country [21] 0 0
France
State/province [21] 0 0
Caen Cedex 5
Country [22] 0 0
France
State/province [22] 0 0
Dijon
Country [23] 0 0
France
State/province [23] 0 0
La Tronche
Country [24] 0 0
France
State/province [24] 0 0
Lyon Cedex 08
Country [25] 0 0
France
State/province [25] 0 0
Paris cedex 20
Country [26] 0 0
France
State/province [26] 0 0
Paris
Country [27] 0 0
France
State/province [27] 0 0
Saint-Herblain cedex
Country [28] 0 0
France
State/province [28] 0 0
Villejuif Cedex
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Essen
Country [31] 0 0
Germany
State/province [31] 0 0
Esslingen
Country [32] 0 0
Germany
State/province [32] 0 0
Gauting
Country [33] 0 0
Germany
State/province [33] 0 0
Hamburg
Country [34] 0 0
Germany
State/province [34] 0 0
Hannover
Country [35] 0 0
Germany
State/province [35] 0 0
Heidelberg
Country [36] 0 0
Germany
State/province [36] 0 0
Mainz
Country [37] 0 0
Germany
State/province [37] 0 0
Münster
Country [38] 0 0
Hungary
State/province [38] 0 0
Budapest
Country [39] 0 0
Hungary
State/province [39] 0 0
Pecs
Country [40] 0 0
Hungary
State/province [40] 0 0
Törökbálint
Country [41] 0 0
India
State/province [41] 0 0
Chennai
Country [42] 0 0
India
State/province [42] 0 0
Jaipur
Country [43] 0 0
India
State/province [43] 0 0
Maharashtra
Country [44] 0 0
India
State/province [44] 0 0
Mumbai
Country [45] 0 0
India
State/province [45] 0 0
Nashik, Maharashtra
Country [46] 0 0
Israel
State/province [46] 0 0
Kfar Saba
Country [47] 0 0
Israel
State/province [47] 0 0
Petach Tikva
Country [48] 0 0
Israel
State/province [48] 0 0
Tel Hashomer
Country [49] 0 0
Italy
State/province [49] 0 0
Avellino
Country [50] 0 0
Italy
State/province [50] 0 0
Aviano (PN)
Country [51] 0 0
Italy
State/province [51] 0 0
Bergamo
Country [52] 0 0
Italy
State/province [52] 0 0
Genova
Country [53] 0 0
Italy
State/province [53] 0 0
Milano
Country [54] 0 0
Italy
State/province [54] 0 0
Monza (mi)
Country [55] 0 0
Italy
State/province [55] 0 0
Ravenna
Country [56] 0 0
Italy
State/province [56] 0 0
Roma
Country [57] 0 0
Korea, Republic of
State/province [57] 0 0
Goyang
Country [58] 0 0
Korea, Republic of
State/province [58] 0 0
Hwasun
Country [59] 0 0
Korea, Republic of
State/province [59] 0 0
Seoul
Country [60] 0 0
Mexico
State/province [60] 0 0
Distrito Federal
Country [61] 0 0
Netherlands
State/province [61] 0 0
Maastricht
Country [62] 0 0
Netherlands
State/province [62] 0 0
Nieuwegein
Country [63] 0 0
Peru
State/province [63] 0 0
Arequipa
Country [64] 0 0
Peru
State/province [64] 0 0
La Victoria
Country [65] 0 0
Poland
State/province [65] 0 0
Gdansk
Country [66] 0 0
Poland
State/province [66] 0 0
Olsztyn
Country [67] 0 0
Poland
State/province [67] 0 0
Otwock
Country [68] 0 0
Poland
State/province [68] 0 0
Warszawa
Country [69] 0 0
Russian Federation
State/province [69] 0 0
Obninsk
Country [70] 0 0
Russian Federation
State/province [70] 0 0
St. Petersburg
Country [71] 0 0
Spain
State/province [71] 0 0
A Coruña
Country [72] 0 0
Spain
State/province [72] 0 0
Barcelona
Country [73] 0 0
Spain
State/province [73] 0 0
Madrid
Country [74] 0 0
Spain
State/province [74] 0 0
Mataró
Country [75] 0 0
Spain
State/province [75] 0 0
Málaga
Country [76] 0 0
Spain
State/province [76] 0 0
Valencia
Country [77] 0 0
Taiwan
State/province [77] 0 0
Kaohsiung
Country [78] 0 0
Taiwan
State/province [78] 0 0
Taichung
Country [79] 0 0
Taiwan
State/province [79] 0 0
Tainan
Country [80] 0 0
Taiwan
State/province [80] 0 0
Taipei
Country [81] 0 0
Taiwan
State/province [81] 0 0
Taoyuan
Country [82] 0 0
Ukraine
State/province [82] 0 0
Dnipropetrovks
Country [83] 0 0
Ukraine
State/province [83] 0 0
Donetsk
Country [84] 0 0
Ukraine
State/province [84] 0 0
Kharkiv
Country [85] 0 0
Ukraine
State/province [85] 0 0
Kyiv
Country [86] 0 0
United Kingdom
State/province [86] 0 0
Brighton
Country [87] 0 0
United Kingdom
State/province [87] 0 0
Dundee
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Exeter
Country [89] 0 0
United Kingdom
State/province [89] 0 0
London
Country [90] 0 0
United Kingdom
State/province [90] 0 0
Maidstone
Country [91] 0 0
United Kingdom
State/province [91] 0 0
Manchester
Country [92] 0 0
United Kingdom
State/province [92] 0 0
Sutton, Surrey
Country [93] 0 0
United Kingdom
State/province [93] 0 0
Truro, Cornwall

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

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective of this randomized, open-label, active-controlled, multi-center trial
is to determine the efficacy of BIBW 2992 given as an add-on to chemotherapy in patients with
NSCLC Stage IIIb or IV progressing after BIBW 2992 monotherapy compared to chemotherapy alone
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. Additional information on the health-related quality of
life (HRQOL) will be collected.
Trial website
https://clinicaltrials.gov/show/NCT01085136
Trial related presentations / publications
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
Other publications