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

NCT00525148 | Completed Phase 2 Results

• 1 other identifier: 1200.22
• Study Type: interventional
• Target: 129
• Locations: 2 countries
• Sites: 30

Brief Summary

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.

Conditions

Carcinoma, Non-Small-Cell Lung

Outcome Measures

Primary Outcomes (1)

• Objective Response (OR) as Determined by RECIST 1.0

  Objective response (OR) was assessed for all treated patients by independent review as determined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0. OR included complete response (CR) and partial response (PR), where CR or PR must have been confirmed by a subsequent response in ≥28 days.

  Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.

Secondary Outcomes (9)

• Clinical Benefit as Determined by RECIST 1.0

  Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.

• Duration of Clinical Benefit

  Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.

• Duration of Objective Response

  Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.

• Time to Objective Response

  Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.

• Progression-free Survival

  Response assessment is done at end of Week 4 (after Course 1), Week 8 (after Course 2), Week 12 (after Course 3) and at 8-week intervals thereafter, up to 93 months.

Study Arms (1)

BIBW 2992

EXPERIMENTAL

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

Interventions

BIBW 2992 DRUG

This is an open label study. Patients are treated with BIBW 2992 until disease progression or undue AEs

BIBW 2992

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with pathologically confirmed diagnosis of NSCLC Stage IIIB (with pleural effusion) adenocarcinoma or Stage IV adenocarcinoma.
• Presence of activating mutation(s) in exon 18 to exon 21 of the EGFR-receptor confirmed by direct DNA sequencing of NSCLC tumor tissue.
• 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.
• 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.
• Male or female patient aged 18 years.
• Life expectancy of at least three (3) months.
• Written informed consents that is consistent with ICH-GCP guidelines.
• Eastern Cooperative Oncology Group (ECOG) performance score 0, 1 or 2.

You may not qualify if:

• More than one (1) prior cytotoxic chemotherapy treatment regimen for relapsed or metastatic NSCLC.
• 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.
• Previous treatment with erlotinib (Tarceva®), gefitinib (Iressa®) or any other EGFR inhibiting small molecule or antibody.
• 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.
• 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.
• 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.
• Other malignancies diagnosed within the past five (5) years (other than non-melanomatous skin cancer and in situ cervical cancer).
• Radiotherapy within the past 2 weeks prior to treatment with the trial drug.
• Patients with any serious active infection (i.e., requiring an IV antibiotic, antifungal, or antiviral agents).
• Patients with known HIV, active hepatitis B or active hepatitis C.
• Known or suspected active drug or alcohol abuse.
• 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.
• Pregnancy or breast feeding.
• Patient unable to comply with the protocol.
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (30)

1200.22.28 Boehringer Ingelheim Investigational Site

Bakersfield, California, United States

Location

1200.22.32 Boehringer Ingelheim Investigational Site

Beverly Hills, California, United States

Location

1200.22.4 Boehringer Ingelheim Investigational Site

Mission Hills, California, United States

Location

1200.22.16 Boehringer Ingelheim Investigational Site

Orange, California, United States

Location

1200.22.19 Boehringer Ingelheim Investigational Site

Fort Lauderdale, Florida, United States

Location

1200.22.29 Boehringer Ingelheim Investigational Site

North Miami Beach, Florida, United States

Location

1200.22.10 Boehringer Ingelheim Investigational Site

Atlanta, Georgia, United States

Location

1200.22.18 Boehringer Ingelheim Investigational Site

Chicago, Illinois, United States

Location

1200.22.3 Boehringer Ingelheim Investigational Site

Bethesda, Maryland, United States

Location

1200.22.14 Boehringer Ingelheim Investigational Site

Boston, Massachusetts, United States

Location

1200.22.24 Boehringer Ingelheim Investigational Site

Flint, Michigan, United States

Location

1200.22.5 Boehringer Ingelheim Investigational Site

Minneapolis, Minnesota, United States

Location

1200.22.15 Boehringer Ingelheim Investigational Site

New York, New York, United States

Location

1200.22.26 Boehringer Ingelheim Investigational Site

New York, New York, United States

Location

1200.22.1 Boehringer Ingelheim Investigational Site

Rochester, New York, United States

Location

1200.22.27 Boehringer Ingelheim Investigational Site

Syracuse, New York, United States

Location

1200.22.25 Boehringer Ingelheim Investigational Site

Valhalla, New York, United States

Location

1200.22.6 Boehringer Ingelheim Investigational Site

Canton, Ohio, United States

Location

1200.22.7 Boehringer Ingelheim Investigational Site

Wynnewood, Pennsylvania, United States

Location

1200.22.22 Boehringer Ingelheim Investigational Site

Mt. Pleasant, South Carolina, United States

Location

1200.22.31 Boehringer Ingelheim Investigational Site

Fairfax, Virginia, United States

Location

1200.22.40 Boehringer Ingelheim Investigational Site

Renton, Washington, United States

Location

1200.22.33 Boehringer Ingelheim Investigational Site

Seattle, Washington, United States

Location

1200.22.88604 Taichung Veterans General Hospital

Taichung, Taiwan

Location

1200.22.88605 China Medical University Hospital

Taichung, Taiwan

Location

1200.22.88606 Boehringer Ingelheim Investigational Site

Tainan, Taiwan

Location

1200.22.88601 National Taiwan University Hospital

Taipei, Taiwan

Location

1200.22.88602 Veterans General Hospital

Taipei, Taiwan

Location

1200.22.88607 Boehringer Ingelheim Investigational Site

Taipei, Taiwan

Location

1200.22.88603 Chang Gung Memorial Hosp-Linkou

Taoyuan District, Taiwan

Location

Related Publications (2)

• Yang JC, Sequist LV, Geater SL, Tsai CM, Mok TS, Schuler M, Yamamoto N, Yu CJ, Ou SH, Zhou C, Massey D, Zazulina V, Wu YL. Clinical activity of afatinib in patients with advanced non-small-cell lung cancer harbouring uncommon EGFR mutations: a combined post-hoc analysis of LUX-Lung 2, LUX-Lung 3, and LUX-Lung 6. Lancet Oncol. 2015 Jul;16(7):830-8. doi: 10.1016/S1470-2045(15)00026-1. Epub 2015 Jun 4.

  PMID: 26051236 DERIVED

• Yang JC, Shih JY, Su WC, Hsia TC, Tsai CM, Ou SH, Yu CJ, Chang GC, Ho CL, Sequist LV, Dudek AZ, Shahidi M, Cong XJ, Lorence RM, Yang PC, Miller VA. Afatinib for patients with lung adenocarcinoma and epidermal growth factor receptor mutations (LUX-Lung 2): a phase 2 trial. Lancet Oncol. 2012 May;13(5):539-48. doi: 10.1016/S1470-2045(12)70086-4. Epub 2012 Mar 26.

  PMID: 22452895 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Afatinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Amides; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Study Officials

• Boehringer Ingelheim

  Boehringer Ingelheim

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 3, 2007
• First Posted: September 5, 2007
• Study Start: August 1, 2007
• Primary Completion: February 1, 2010
• Study Completion: August 1, 2015
• Last Updated: September 16, 2016
• Results First Posted: October 14, 2013

Record last verified: 2016-07

Locations

TW (7); US (23)