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

NCT ID: NCT01085136

Last Updated: 2017-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1154 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-02-28
• Study Completion Date: 2016-01-31

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Investigator's choice of chemotherapy

Patients will be treated with investigator's choice of chemotherapy

Group Type: ACTIVE_COMPARATOR

Investigator´s choice of chemotherapy

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

BIBW 2992

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

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 Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Boehringer Ingelheim

Role: STUDY_CHAIR

Boehringer Ingelheim

Locations

Boehringer Ingelheim Investigational Site

Buenos Aires, , Argentina

Boehringer Ingelheim Investigational Site

Kingswood, New South Wales, Australia

Boehringer Ingelheim Investigational Site

South Brisbane, Queensland, Australia

Boehringer Ingelheim Investigational Site

Box Hill, Victoria, Australia

Boehringer Ingelheim Investigational Site

Fitzroy, Victoria, Australia

Boehringer Ingelheim Investigational Site

Wodonga, Victoria, Australia

Boehringer Ingelheim Investigational Site

Salzburg, , Austria

Boehringer Ingelheim Investigational Site

Aalst, , Belgium

Boehringer Ingelheim Investigational Site

Brussels, , Belgium

Boehringer Ingelheim Investigational Site

Duffel, , Belgium

Boehringer Ingelheim Investigational Site

La Louvière, , Belgium

Boehringer Ingelheim Investigational Site

Liège, , Belgium

Boehringer Ingelheim Investigational Site

Middelheim, , Belgium

Boehringer Ingelheim Investigational Site

Ottignies, , Belgium

Boehringer Ingelheim Investigational Site

Porto Alegre, , Brazil

Boehringer Ingelheim Investigational Site

Beijing, , China

Boehringer Ingelheim Investigational Site

Changchun, , China

Boehringer Ingelheim Investigational Site

Chengdu, , China

Boehringer Ingelheim Investigational Site

Fuzhou, , China

Boehringer Ingelheim Investigational Site

Guangzhou, , China

Boehringer Ingelheim Investigational Site

Hangzhou, , China

Boehringer Ingelheim Investigational Site

Nanjing, , China

Boehringer Ingelheim Investigational Site

Shanghai, , China

Boehringer Ingelheim Investigational Site

Helsinki, , Finland

Boehringer Ingelheim Investigational Site

Bayonne, , France

Boehringer Ingelheim Investigational Site

Caen, , France

Boehringer Ingelheim Investigational Site

Dijon, , France

Boehringer Ingelheim Investigational Site

La Tronche, , France

Boehringer Ingelheim Investigational Site

Lyon, , France

Boehringer Ingelheim Investigational Site

Paris, , France

Boehringer Ingelheim Investigational Site

Saint-Herblain, , France

Boehringer Ingelheim Investigational Site

Villejuif, , France

Boehringer Ingelheim Investigational Site

Berlin, , Germany

Boehringer Ingelheim Investigational Site

Essen, , Germany

Boehringer Ingelheim Investigational Site

Esslingen am Neckar, , Germany

Boehringer Ingelheim Investigational Site

Gauting, , Germany

Boehringer Ingelheim Investigational Site

Hamburg, , Germany

Boehringer Ingelheim Investigational Site

Hanover, , Germany

Boehringer Ingelheim Investigational Site

Heidelberg, , Germany

Boehringer Ingelheim Investigational Site

Mainz, , Germany

Boehringer Ingelheim Investigational Site

Münster, , Germany

Boehringer Ingelheim Investigational Site

Budapest, , Hungary

Boehringer Ingelheim Investigational Site

Pécs, , Hungary

Boehringer Ingelheim Investigational Site

Törökbálint, , Hungary

Boehringer Ingelheim Investigational Site

Chennai, , India

Boehringer Ingelheim Investigational Site

Jaipur, , India

Boehringer Ingelheim Investigational Site

Maharashtra, , India

Boehringer Ingelheim Investigational Site

Mumbai, , India

Boehringer Ingelheim Investigational Site

Nashik, Maharashtra, , India

Boehringer Ingelheim Investigational Site

Kfar Saba, , Israel

Boehringer Ingelheim Investigational Site

Petah Tikva, , Israel

Boehringer Ingelheim Investigational Site

Tel Litwinsky, , Israel

Boehringer Ingelheim Investigational Site

Avellino, , Italy

Boehringer Ingelheim Investigational Site

Aviano (PN), , Italy

Boehringer Ingelheim Investigational Site

Bergamo, , Italy

Boehringer Ingelheim Investigational Site

Genova, , Italy

Boehringer Ingelheim Investigational Site

Milan, , Italy

Boehringer Ingelheim Investigational Site

Monza (mi), , Italy

Boehringer Ingelheim Investigational Site

Ravenna, , Italy

Boehringer Ingelheim Investigational Site

Roma, , Italy

Boehringer Ingelheim Investigational Site

Distrito Federal, , Mexico

Boehringer Ingelheim Investigational Site

Maastricht, , Netherlands

Boehringer Ingelheim Investigational Site

Nieuwegein, , Netherlands

Boehringer Ingelheim Investigational Site

Arequipa, , Peru

Boehringer Ingelheim Investigational Site

La Victoria, , Peru

Boehringer Ingelheim Investigational Site

Gdansk, , Poland

Boehringer Ingelheim Investigational Site

Olsztyn, , Poland

Boehringer Ingelheim Investigational Site

Otwock, , Poland

Boehringer Ingelheim Investigational Site

Warsaw, , Poland

Boehringer Ingelheim Investigational Site

Obninsk, , Russia

Boehringer Ingelheim Investigational Site

Saint Petersburg, , Russia

Boehringer Ingelheim Investigational Site

Goyang, , South Korea

Boehringer Ingelheim Investigational Site

Hwasun, , South Korea

Boehringer Ingelheim Investigational Site

Seoul, , South Korea

Boehringer Ingelheim Investigational Site

A Coruña, , Spain

Boehringer Ingelheim Investigational Site

Barcelona, , Spain

Boehringer Ingelheim Investigational Site

Madrid, , Spain

Boehringer Ingelheim Investigational Site

Mataró, , Spain

Boehringer Ingelheim Investigational Site

Málaga, , Spain

Boehringer Ingelheim Investigational Site

Valencia, , Spain

Boehringer Ingelheim Investigational Site

Kaohsiung City, , Taiwan

Boehringer Ingelheim Investigational Site

Taichung, , Taiwan

Boehringer Ingelheim Investigational Site

Tainan City, , Taiwan

Boehringer Ingelheim Investigational Site

Taipei, , Taiwan

Boehringer Ingelheim Investigational Site

Taoyuan District, , Taiwan

Boehringer Ingelheim Investigational Site

Dnipropetrovks, , Ukraine

Boehringer Ingelheim Investigational Site

Donetsk, , Ukraine

Boehringer Ingelheim Investigational Site

Kharkiv, , Ukraine

Boehringer Ingelheim Investigational Site

Kyiv, , Ukraine

Boehringer Ingelheim Investigational Site

Brighton, , United Kingdom

Boehringer Ingelheim Investigational Site

Dundee, , United Kingdom

Boehringer Ingelheim Investigational Site

Exeter, , United Kingdom

Boehringer Ingelheim Investigational Site

London, , United Kingdom

Boehringer Ingelheim Investigational Site

Maidstone, , United Kingdom

Boehringer Ingelheim Investigational Site

Manchester, , United Kingdom

Boehringer Ingelheim Investigational Site

Sutton, Surrey, , United Kingdom

Boehringer Ingelheim Investigational Site

Truro, Cornwall, , United Kingdom

Countries

Argentina; Australia; Austria; Belgium; Brazil; China; Finland; France; Germany; Hungary; India; Israel; Italy; Mexico; Netherlands; Peru; Poland; Russia; South Korea; Spain; Taiwan; Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 26646759 (View on PubMed)

Other Identifiers

2009-014563-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1200.42

Identifier Type: -

Identifier Source: org_study_id