Clinical trial NCT01085136: 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
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Carcinoma, Non-Small-Cell Lung
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2010-03-11
Enrollment: 1154
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: 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.


Eligibility 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

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.

Primary outcomes:
measure: Progression Free Survival (Part B)
timeFrame: From randomization until disease progression or death; Up to 32 months
Secondary outcomes:
measure: Progression Free Survival (Part A)
timeFrame: From first dose administration until disease progression or death; Up to 51 months
measure: Overall Survival (Part B)
timeFrame: From randomization until death; Up to 32 months
measure: Objective Response (Part A)
timeFrame: Post baseline tumour-imaging was performed at every 6 weeks thereafter until disease progression; upto 51 months
measure: Objective Response (Part B)
timeFrame: Post baseline tumour-imaging was performed at every 8 weeks thereafter until disease progression; up to 32 Months
measure: Intensity and Incidence of Adverse Events (AEs) for Part A & Part B.
timeFrame: 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)
Other outcomes:
Locations:
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Boehringer Ingelheim Investigational Site
city: Kingswood
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: New South Wales
city: South Brisbane
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: Queensland
city: Box Hill
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: Victoria
city: Fitzroy
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: Victoria
city: Wodonga
country: Australia
facility: Boehringer Ingelheim Investigational Site
state: Victoria
city: Salzburg
country: Austria
facility: Boehringer Ingelheim Investigational Site
city: Aalst
country: Belgium
facility: Boehringer Ingelheim Investigational Site
city: Bruxelles
country: Belgium
facility: Boehringer Ingelheim Investigational Site
city: Duffel
country: Belgium
facility: Boehringer Ingelheim Investigational Site
city: La Louvière
country: Belgium
facility: Boehringer Ingelheim Investigational Site
city: Liège
country: Belgium
facility: Boehringer Ingelheim Investigational Site
city: Middelheim
country: Belgium
facility: Boehringer Ingelheim Investigational Site
city: Ottignies
country: Belgium
facility: Boehringer Ingelheim Investigational Site
city: Porto Alegre
country: Brazil
facility: Boehringer Ingelheim Investigational Site
city: Beijing
country: China
facility: Boehringer Ingelheim Investigational Site
city: Changchun
country: China
facility: Boehringer Ingelheim Investigational Site
city: Chengdu
country: China
facility: Boehringer Ingelheim Investigational Site
city: Fuzhou
country: China
facility: Boehringer Ingelheim Investigational Site
city: Guangzhou
country: China
facility: Boehringer Ingelheim Investigational Site
city: Hangzhou
country: China
facility: Boehringer Ingelheim Investigational Site
city: Nanjing
country: China
facility: Boehringer Ingelheim Investigational Site
city: Shanghai
country: China
facility: Boehringer Ingelheim Investigational Site
city: Helsinki
country: Finland
facility: Boehringer Ingelheim Investigational Site
city: Bayonne
country: France
facility: Boehringer Ingelheim Investigational Site
city: Caen Cedex 5
country: France
facility: Boehringer Ingelheim Investigational Site
city: Dijon
country: France
facility: Boehringer Ingelheim Investigational Site
city: La Tronche
country: France
facility: Boehringer Ingelheim Investigational Site
city: Lyon Cedex 08
country: France
facility: Boehringer Ingelheim Investigational Site
city: Paris cedex 20
country: France
facility: Boehringer Ingelheim Investigational Site
city: Paris
country: France
facility: Boehringer Ingelheim Investigational Site
city: Saint-Herblain cedex
country: France
facility: Boehringer Ingelheim Investigational Site
city: Villejuif Cedex
country: France
facility: Boehringer Ingelheim Investigational Site
city: Berlin
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Essen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Esslingen
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Gauting
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hamburg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Hannover
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Heidelberg
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Mainz
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Münster
country: Germany
facility: Boehringer Ingelheim Investigational Site
city: Budapest
country: Hungary
facility: Boehringer Ingelheim Investigational Site
city: Pecs
country: Hungary
facility: Boehringer Ingelheim Investigational Site
city: Törökbálint
country: Hungary
facility: Boehringer Ingelheim Investigational Site
city: Chennai
country: India
facility: Boehringer Ingelheim Investigational Site
city: Jaipur
country: India
facility: Boehringer Ingelheim Investigational Site
city: Maharashtra
country: India
facility: Boehringer Ingelheim Investigational Site
city: Mumbai
country: India
facility: Boehringer Ingelheim Investigational Site
city: Nashik, Maharashtra
country: India
facility: Boehringer Ingelheim Investigational Site
city: Kfar Saba
country: Israel
facility: Boehringer Ingelheim Investigational Site
city: Petach Tikva
country: Israel
facility: Boehringer Ingelheim Investigational Site
city: Tel Hashomer
country: Israel
facility: Boehringer Ingelheim Investigational Site
city: Avellino
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Aviano (PN)
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Bergamo
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Genova
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Milano
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Monza (mi)
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Ravenna
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Roma
country: Italy
facility: Boehringer Ingelheim Investigational Site
city: Goyang
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Hwasun
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Seoul
country: Korea, Republic of
facility: Boehringer Ingelheim Investigational Site
city: Distrito Federal
country: Mexico
facility: Boehringer Ingelheim Investigational Site
city: Maastricht
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Nieuwegein
country: Netherlands
facility: Boehringer Ingelheim Investigational Site
city: Arequipa
country: Peru
facility: Boehringer Ingelheim Investigational Site
city: La Victoria
country: Peru
facility: Boehringer Ingelheim Investigational Site
city: Gdansk
country: Poland
facility: Boehringer Ingelheim Investigational Site
city: Olsztyn
country: Poland
facility: Boehringer Ingelheim Investigational Site
city: Otwock
country: Poland
facility: Boehringer Ingelheim Investigational Site
city: Warszawa
country: Poland
facility: Boehringer Ingelheim Investigational Site
city: Obninsk
country: Russian Federation
facility: Boehringer Ingelheim Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Boehringer Ingelheim Investigational Site
city: A Coruña
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Barcelona
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Madrid
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Mataró
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Málaga
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Valencia
country: Spain
facility: Boehringer Ingelheim Investigational Site
city: Kaohsiung
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Taichung
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Tainan
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Taipei
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Taoyuan
country: Taiwan
facility: Boehringer Ingelheim Investigational Site
city: Dnipropetrovks
country: Ukraine
facility: Boehringer Ingelheim Investigational Site
city: Donetsk
country: Ukraine
facility: Boehringer Ingelheim Investigational Site
city: Kharkiv
country: Ukraine
facility: Boehringer Ingelheim Investigational Site
city: Kyiv
country: Ukraine
facility: Boehringer Ingelheim Investigational Site
city: Brighton
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Dundee
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Exeter
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: London
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Maidstone
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Manchester
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Sutton, Surrey
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
city: Truro, Cornwall
country: United Kingdom
facility: Boehringer Ingelheim Investigational Site
Study officials:
affiliation: Boehringer Ingelheim
name: Boehringer Ingelheim
role: STUDY_CHAIR
References:
citation: Schuler M, Yang JC, Park K, Kim JH, Bennouna J, Chen YM, Chouaid C, De Marinis F, Feng JF, Grossi F, Kim DW, Liu X, Lu S, Strausz J, Vinnyk Y, Wiewrodt R, Zhou C, Wang B, Chand VK, Planchard D; LUX-Lung 5 Investigators. Afatinib beyond progression in patients with non-small-cell lung cancer following chemotherapy, erlotinib/gefitinib and afatinib: phase III randomized LUX-Lung 5 trial. Ann Oncol. 2016 Mar;27(3):417-23. doi: 10.1093/annonc/mdv597. Epub 2015 Dec 8.