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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim
ClinicalTrials.gov Identifier:
NCT00525148
First received: September 3, 2007
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
Drug: BIBW 2992
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: LUX Lung 2 A Phase II Single-arm Trial of BIBW 2992 in Non-small Cell Lung Cancer Patients With EGFR Activating Mutations

Resource links provided by NLM:


Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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).


Enrollment: 129
Study Start Date: August 2007
Estimated Study Completion Date: March 2014
Primary Completion Date: February 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: BIBW 2992
This is an open label study. Patients are treated with BIBW 2992 until disease progression or undue AEs

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00525148

  Show 30 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Investigators
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

No publications provided by Boehringer Ingelheim

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT00525148     History of Changes
Other Study ID Numbers: 1200.22
Study First Received: September 3, 2007
Results First Received: August 8, 2013
Last Updated: January 24, 2014
Health Authority: Taiwan: Department of Health, Executive Yuan, Taiwan
United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on April 15, 2014