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

Carcinoma, Non-Small-Cell Lung Clinical Trial

Official 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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01085136
• Other study ID #: 1200.42
• Secondary ID: 2009-014563-39
• Status: Completed
• Phase: Phase 3
• First received: March 10, 2010
• Last updated: February 9, 2016
• Start date: February 2010
• Est. completion date: January 2016

Study information

• Verified date: February 2016
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia MedicaAustralia: Dept of Health and Ageing Therapeutic Goods AdminAustria: Medicines and Medical Devices AgencyBelgium: Federal Agency for Medicinal and Health ProductsBrazil: National Health Surveillance AgencyChina: Food and Drug AdministrationFinland: Finnish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesHungary: National Institute of PharmacyIndia: Drugs Controller General of IndiaIsrael: Israeli Health Ministry Pharmaceutical AdministrationItaly: Ethics CommitteeMexico: Federal Commission for Sanitary Risks ProtectionNetherlands: Central Committee Research Involving Human SubjectsPeru: Ministry of HealthPoland: Registration Medicinal Product Medical Device Biocidal ProductRussia: Pharmacological Committee, Ministry of HealthSouth Korea: Ministry of Food and Drug Safety (MFDS)Spain: Spanish Agency of MedicinesTaiwan: Department of HealthUkraine: State Pharmacological Center - Ministry of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1155
• Est. completion date: January 2016
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• 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
• 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

Locations

Country	Name	City	State
Argentina	1200.42.54006 Boehringer Ingelheim Investigational Site	Ciudad Autonoma de Buenos Aires
Australia	1200.42.61002 Boehringer Ingelheim Investigational Site	Box Hill	Victoria
Australia	1200.42.61001 Boehringer Ingelheim Investigational Site	Fitzroy	Victoria
Australia	1200.42.61004 Boehringer Ingelheim Investigational Site	Kingswood	New South Wales
Australia	1200.42.61005 Boehringer Ingelheim Investigational Site	South Brisbane	Queensland
Australia	1200.42.61003 Boehringer Ingelheim Investigational Site	Wodonga	Victoria
Austria	1200.42.43002 Boehringer Ingelheim Investigational Site	Salzburg
Belgium	1200.42.32007 Boehringer Ingelheim Investigational Site	Aalst
Belgium	1200.42.32001 Boehringer Ingelheim Investigational Site	Bruxelles
Belgium	1200.42.32006 Boehringer Ingelheim Investigational Site	Duffel
Belgium	1200.42.32004 Boehringer Ingelheim Investigational Site	La Louvière
Belgium	1200.42.32002 Boehringer Ingelheim Investigational Site	Liège
Belgium	1200.42.32005 Boehringer Ingelheim Investigational Site	Middelheim
Belgium	1200.42.32003 Boehringer Ingelheim Investigational Site	Ottignies
Brazil	1200.42.55004 Boehringer Ingelheim Investigational Site	Porto Alegre
China	1200.42.86007 Boehringer Ingelheim Investigational Site	Beijing
China	1200.42.86008 Boehringer Ingelheim Investigational Site	Changchun
China	1200.42.86003 Boehringer Ingelheim Investigational Site	Chengdu
China	1200.42.86004 Boehringer Ingelheim Investigational Site	Fuzhou
China	1200.42.86005 Boehringer Ingelheim Investigational Site	Fuzhou
China	1200.42.86006 Boehringer Ingelheim Investigational Site	Guangzhou
China	1200.42.86011 Boehringer Ingelheim Investigational Site	Hangzhou
China	1200.42.86012 Boehringer Ingelheim Investigational Site	Hangzhou
China	1200.42.86009 Boehringer Ingelheim Investigational Site	Nanjing
China	1200.42.86010 Boehringer Ingelheim Investigational Site	Nanjing
China	1200.42.86002 Boehringer Ingelheim Investigational Site	Shanghai
China	1200.42.86013 Boehringer Ingelheim Investigational Site	Shanghai
Finland	1200.42.35801 Boehringer Ingelheim Investigational Site	Helsinki
Finland	1200.42.35802 Boehringer Ingelheim Investigational Site	Helsinki
France	1200.42.33013 Boehringer Ingelheim Investigational Site	Bayonne
France	1200.42.33003 Boehringer Ingelheim Investigational Site	Caen Cedex 5
France	1200.42.33011 Boehringer Ingelheim Investigational Site	Caen cedex 5
France	1200.42.33010 Boehringer Ingelheim Investigational Site	Dijon
France	1200.42.33004 Boehringer Ingelheim Investigational Site	La Tronche
France	1200.42.33005 Boehringer Ingelheim Investigational Site	Lyon Cedex 08
France	1200.42.33002 Boehringer Ingelheim Investigational Site	Paris
France	1200.42.33001 Boehringer Ingelheim Investigational Site	Paris cedex 20
France	1200.42.33007 Boehringer Ingelheim Investigational Site	Saint-Herblain cedex
France	1200.42.33006 Boehringer Ingelheim Investigational Site	Villejuif Cedex
Germany	1200.42.49002 Boehringer Ingelheim Investigational Site	Berlin
Germany	1200.42.49001 Boehringer Ingelheim Investigational Site	Essen
Germany	1200.42.49013 Boehringer Ingelheim Investigational Site	Esslingen
Germany	1200.42.49003 Boehringer Ingelheim Investigational Site	Gauting
Germany	1200.42.49014 Boehringer Ingelheim Investigational Site	Hamburg
Germany	1200.42.49006 Boehringer Ingelheim Investigational Site	Hannover
Germany	1200.42.49007 Boehringer Ingelheim Investigational Site	Heidelberg
Germany	1200.42.49009 Boehringer Ingelheim Investigational Site	Mainz
Germany	1200.42.49010 Boehringer Ingelheim Investigational Site	Münster
Hungary	1200.42.36004 Boehringer Ingelheim Investigational Site	Budapest
Hungary	1200.42.36005 Boehringer Ingelheim Investigational Site	Pecs
Hungary	1200.42.36001 Boehringer Ingelheim Investigational Site	Törökbálint
India	1200.42.91003 Boehringer Ingelheim Investigational Site	Chennai
India	1200.42.91004 Boehringer Ingelheim Investigational Site	Jaipur
India	1200.42.91002 Boehringer Ingelheim Investigational Site	Maharashtra
India	1200.42.91001 Boehringer Ingelheim Investigational Site	Mumbai
India	1200.42.91006 Boehringer Ingelheim Investigational Site	Nashik, Maharashtra
Israel	1200.42.97203 Boehringer Ingelheim Investigational Site	Kfar Saba
Israel	1200.42.97204 Boehringer Ingelheim Investigational Site	Petach Tikva
Israel	1200.42.97201 Boehringer Ingelheim Investigational Site	Tel Hashomer
Italy	1200.42.39005 Boehringer Ingelheim Investigational Site	Avellino
Italy	1200.42.39004 Boehringer Ingelheim Investigational Site	Aviano (PN)
Italy	1200.42.39008 Boehringer Ingelheim Investigational Site	Bergamo
Italy	1200.42.39002 Boehringer Ingelheim Investigational Site	Genova
Italy	1200.42.39007 Boehringer Ingelheim Investigational Site	Milano
Italy	1200.42.39003 Boehringer Ingelheim Investigational Site	Monza (mi)
Italy	1200.42.39009 Boehringer Ingelheim Investigational Site	Ravenna
Italy	1200.42.39001 Boehringer Ingelheim Investigational Site	Roma
Korea, Republic of	1200.42.82005 Boehringer Ingelheim Investigational Site	Goyang
Korea, Republic of	1200.42.82006 Boehringer Ingelheim Investigational Site	Hwasun
Korea, Republic of	1200.42.82001 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1200.42.82002 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1200.42.82003 Boehringer Ingelheim Investigational Site	Seoul
Korea, Republic of	1200.42.82004 Boehringer Ingelheim Investigational Site	Seoul
Mexico	1200.42.52003 Boehringer Ingelheim Investigational Site	Distrito Federal
Netherlands	1200.42.31005 Boehringer Ingelheim Investigational Site	Maastricht
Netherlands	1200.42.31006 Boehringer Ingelheim Investigational Site	Nieuwegein
Peru	1200.42.51002 Boehringer Ingelheim Investigational Site	Arequipa
Peru	1200.42.51001 Boehringer Ingelheim Investigational Site	La Victoria
Poland	1200.42.48006 Boehringer Ingelheim Investigational Site	Gdansk
Poland	1200.42.48002 Boehringer Ingelheim Investigational Site	Olsztyn
Poland	1200.42.48004 Boehringer Ingelheim Investigational Site	Otwock
Poland	1200.42.48001 Boehringer Ingelheim Investigational Site	Warszawa
Russian Federation	1200.42.70006 Boehringer Ingelheim Investigational Site	Obninsk
Russian Federation	1200.42.70004 Boehringer Ingelheim Investigational Site	St. Petersburg
Russian Federation	1200.42.70005 Boehringer Ingelheim Investigational Site	St. Petersburg
Spain	1200.42.34005 Boehringer Ingelheim Investigational Site	A Coruña
Spain	1200.42.34008 Boehringer Ingelheim Investigational Site	Barcelona
Spain	1200.42.34001 Boehringer Ingelheim Investigational Site	Madrid
Spain	1200.42.34002 Boehringer Ingelheim Investigational Site	Madrid
Spain	1200.42.34007 Boehringer Ingelheim Investigational Site	Málaga
Spain	1200.42.34006 Boehringer Ingelheim Investigational Site	Mataró
Spain	1200.42.34003 Boehringer Ingelheim Investigational Site	Valencia
Taiwan	1200.42.88608 Boehringer Ingelheim Investigational Site	Kaohsiung
Taiwan	1200.42.88602 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	1200.42.88605 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	1200.42.88606 Boehringer Ingelheim Investigational Site	Taichung
Taiwan	1200.42.88607 Boehringer Ingelheim Investigational Site	Tainan
Taiwan	1200.42.88601 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1200.42.88603 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1200.42.88609 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1200.42.88610 Boehringer Ingelheim Investigational Site	Taipei
Taiwan	1200.42.88604 Boehringer Ingelheim Investigational Site	Taoyuan
Ukraine	1200.42.38004 Boehringer Ingelheim Investigational Site	Dnipropetrovks
Ukraine	1200.42.38002 Boehringer Ingelheim Investigational Site	Donetsk
Ukraine	1200.42.38001 Boehringer Ingelheim Investigational Site	Kharkiv
Ukraine	1200.42.38003 Boehringer Ingelheim Investigational Site	Kyiv
United Kingdom	1200.42.44003 Boehringer Ingelheim Investigational Site	Brighton
United Kingdom	1200.42.44005 Boehringer Ingelheim Investigational Site	Dundee
United Kingdom	1200.42.44007 Boehringer Ingelheim Investigational Site	Exeter
United Kingdom	1200.42.44004 Boehringer Ingelheim Investigational Site	London
United Kingdom	1200.42.44006 Boehringer Ingelheim Investigational Site	London
United Kingdom	1200.42.44001 Boehringer Ingelheim Investigational Site	Maidstone
United Kingdom	1200.42.44012 Boehringer Ingelheim Investigational Site	Manchester
United Kingdom	1200.42.44008 Boehringer Ingelheim Investigational Site	Sutton, Surrey
United Kingdom	1200.42.44011 Boehringer Ingelheim Investigational Site	Truro, Cornwall

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

Argentina,  Australia,  Austria,  Belgium,  Brazil,  China,  Finland,  France,  Germany,  Hungary,  India,  Israel,  Italy,  Korea, Republic of,  Mexico,  Netherlands,  Peru,  Poland,  Russian Federation,  Spain,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS) Time as Determined by RECIST 1.1 for Part B.	PFS from the day of randomisation to the day of progression according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 for patients randomised to combination therapy with afatinib plus paclitaxel or to investigators choice of chemotherapy.	Every 8 weeks until the final follow-up visit in Part B, up to a total of 10 years.	No
Secondary	Progression Free Survival (PFS) as Determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for Part A	Progression free survival (PFS) as determined by Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 for Part A. PFS from the day of randomisation to the day of progression according to Response Evaluation Criteria in Solid Tumours (RECIST) Version 1.1 for patients treated with Afatinib monotherapy.	tumour assessment was at screening (-28 days to screening) and every 6 weeks until the first follow-up visit in Part A, up to a total of 10 years.	No
Secondary	Overall Survival (OS) as Determined by the Time From Randomization to Death in Part B	Overall survival was calculated as the time from the date of randomisation to the date of death. Patients for whom there was no evidence of death at the time of the analysis were to be censored on the date that they were last known to have been alive.	from the date of randomisation to the date of death, up to a total of 10 years.	No
Secondary	Objective Response Rate According to RECIST 1.1 in Part B	Objective tumour response was defined as a best overall response of complete response (CR) or partial response (PR) as determined by RECIST 1.1 and as assessed by the Investigator. For patients enrolled in Part B, a Part B best overall response was to be based on all responses taken from the start of Part B treatment until the start of any new anticancer therapy or disease progression in Part B. The duration of objective response was defined as the time of first objective response to the time of progression or death, whichever occurred first (or date of censoring for PFS).	tumour assessment was every 8 weeks until the final follow-up visit in Part B, up to a total of 10 years.	No
Secondary	Objective Response According to RECIST 1.1 in Part A	Objective tumour response was defined as a best overall response of CR or PR as determined by RECIST 1.1 and as assessed by the Investigator. For patients enrolled in Part A, this was to be based on all responses taken from the start of treatment until the start of any new anticancer therapy or disease progression. Objective response was analysed descriptively. The duration of objective response was defined as the time of first objective response to the time of progression or death, whichever occurred first (or date of censoring for PFS).	tumour assessment was at screening (-28 days to screening) and every 6 weeks until the first follow-up visit in Part A, up to a total of 10 years.	No