LUX Lung 2 Phase II Single Arm BIBW 2992 "Afatinib" in NSCLC With EGFR Activating Mutations

This study has been completed.
Information provided by (Responsible Party):
Boehringer Ingelheim Identifier:
First received: September 3, 2007
Last updated: August 12, 2015
Last verified: August 2015

September 3, 2007
August 12, 2015
August 2007
February 2010   (final data collection date for primary outcome measure)
Objective Response (OR) [ Time Frame: Baseline to data cut-off for independent review (12 Jan 2011) ] [ Designated as safety issue: No ]
Percentage of participants with best objective response (OR): confirmed complete response (CR) or confirmed partial response (PR) according to RECIST (version 1.0) by independent review.
The primary endpoint will be objective response (CR, PR) as determined by RECIST
Complete list of historical versions of study NCT00525148 on Archive Site
  • Progression-free Survival (PFS) [ Time Frame: From first dose of study medication until progression, death, start of another anti-cancer therapy or last date of tumor imaging for ongoing patients. ] [ Designated as safety issue: No ]
    PFS was defined as the duration of time from the start of treatment until the day of objective tumor progression was confirmed by tumor imaging (PD according to RECIST 1.0) or death by independent review.
  • Overall Survival (OS) [ Time Frame: From first dose of study medication to data cut-off ] [ Designated as safety issue: No ]
    OS was defined as the duration of time from start of treatment to time of death.
  • Clinical Benefit (CB) [ Time Frame: From first dose of study medication to data cut-off ] [ Designated as safety issue: No ]
    Clinical benefit was evaluated by assessment of complete response (CR), partial response (PR) and stable disease (SD) according to RECIST 1.0 by independent review.
  • Duration of OR [ Time Frame: From first dose of study medication to data cut-off ] [ Designated as safety issue: No ]
    Duration of objective response (OR) was measured from the time the criteria for CR or PR (whichever was documented first) were first met until the first date that progressive disease or death was objectively documented (per independent review).
Duration of objective response Clinical benefit determined by RECIST Time to objective response Duration of objective response Progression free survival time Overall survival time Safety of BIBW 2992 PK evaluation
Not Provided
Not Provided
LUX Lung 2 Phase II Single Arm BIBW 2992 "Afatinib" in NSCLC With EGFR Activating Mutations
LUX Lung 2 A Phase II Single-arm Trial of BIBW 2992 in Non-small Cell Lung Cancer Patients With EGFR Activating Mutations
The primary objective of this open-label, single arm Phase II trial is to explore the efficacy of BIBW 2992 defined by the objective response rate (CR, PR) as determined by RECIST criteria in patients with advanced NSCLC Stage IIIB or IV whose tumors harbor activating mutations within exon 18 to exon 21 of the EGFR receptor. Patients progressing or relapsing after one prior cytotoxic chemotherapy regimen as well as chemotherapy naïve patients (only in stage 2) will be allowed to enter into the trial.
Not Provided
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Carcinoma, Non-Small-Cell Lung
Drug: BIBW 2992
This is an open label study. Patients are treated with BIBW 2992 until disease progression or undue AEs
Experimental: BIBW 2992
Patients start continuous once daily oral treatment of BIBW 2992 at high dose, until progression or undue Adverse Events (AEs) develop. Patients can be dose-reduced up to two times if needed after temporary discontinuation of treatment due to drug-related AEs. After protocol amendment 2 (17 Dec 2008), the starting dose of BIBW 2992 was reduced to a medium dose, with 2 possible dose reductions if needed after discontinuation due to drug-related AEs.
Intervention: Drug: BIBW 2992

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
August 2015
February 2010   (final data collection date for primary outcome measure)

Inclusion criteria:

  1. Patients with pathologically confirmed diagnosis of NSCLC Stage IIIB (with pleural effusion) adenocarcinoma or Stage IV adenocarcinoma.
  2. Presence of activating mutation(s) in exon 18 to exon 21 of the EGFR-receptor confirmed by direct DNA sequencing of NSCLC tumor tissue.
  3. Progressive disease following a first line cytotoxic chemotherapy regimen or have recurrent disease after prior neoadjuvant or adjuvant chemotherapy. Patients who have not received first-line cytotoxic chemotherapy can be enrolled in stage 2 of the trial, if the criteria for entering stage 2 are met.
  4. Patients with at least one tumor lesion that can accurately be measured by computed tomography (CT) or magnetic resonance imaging (MRI) in at least one dimension with longest diameter to be recorded as 20 mm using conventional techniques or 10 mm with spiral CT scan.
  5. Male or female patient aged 18 years.
  6. Life expectancy of at least three (3) months.
  7. Written informed consents that is consistent with ICH-GCP guidelines.
  8. Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2.

Exclusion criteria:

  1. More than one (1) prior cytotoxic chemotherapy treatment regimen for relapsed or metastatic NSCLC.
  2. Chemo-, hormone- (other than Megace®) or immunotherapy within the past 4 weeks or within less than four half-lives of the previous drug prior to treatment with the trial drug and/or persistence of toxicities of prior anticancer therapies which are deemed to be clinically relevant.
  3. Previous treatment with erlotinib (Tarceva®), gefitinib (Iressa®) or any other EGFR inhibiting small molecule or antibody.
  4. Brain metastases, which are symptomatic; patients with treated, asymptomatic brain metastases are eligible with stable brain disease for at least four (4) weeks without the requirement for steroids or anti-epileptic therapy.
  5. Significant or recent acute gastrointestinal disorders with diarrhea as a major symptom e.g., Crohns disease, malabsorption, or CTCAE Grade >2 diarrhea of any etiology at baseline.
  6. 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.
  7. Other malignancies diagnosed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer).
  8. Radiotherapy within the past 2 weeks prior to treatment with the trial drug.
  9. Patients with any serious active infection (i.e., requiring an IV antibiotic, antifungal, or antiviral agents).
  10. Patients with known HIV, active hepatitis B or active hepatitis C.
  11. Known or suspected active drug or alcohol abuse.
  12. 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.
  13. Pregnancy or breast feeding.
  14. Patient unable to comply with the protocol.
  15. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure, angina, myocardial infarction, arrhythmia, including New York Heart Association (NYHA) functional classification of 3.
  16. 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.
  17. QTc interval greater than 0.47 second.
  18. Prior treatment with anthracyclines with a cumulative dose of doxorubicin (or equivalent) greater than 400 mg/m2.
  19. Absolute neutrophil count (ANC) less than 1500/mm3.
  20. Platelet count less than 100 000 /mm3.
  21. Bilirubin greater than 1.5 mg / dl (greater than 26 micromol / L, SI unit equivalent).
  22. Aspartate amino transferase (AST) or alanine amino transferase (ALT) greater than three times the upper limit of normal (if related to liver metastases greater than five times the upper limit of normal).
  23. Serum creatinine greater than 1.5 times of the upper normal limit or calculated/measured creatinine clearance equal or less than 45 ml / min.
  24. Patients with known pre-existing interstitial lung disease
18 Years and older   (Adult, Senior)
Contact information is only displayed when the study is recruiting subjects
United States,   Taiwan
Not Provided
Not Provided
Not Provided
Boehringer Ingelheim
Boehringer Ingelheim
Not Provided
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
Boehringer Ingelheim
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP