LUX Lung 2 Phase II Single Arm BIBW 2992 "Afatinib" in NSCLC With EGFR Activating Mutations
- Registration Number
- NCT00525148
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 129
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description BIBW 2992 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.
- Primary Outcome Measures
Name Time Method Objective Response (OR) 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. 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.
- Secondary Outcome Measures
Name Time Method Cpre,ss,29 -0:05h (pre-dose) on Day 29 Predose concentration of the analyte in plasma at steady state immediately before administration of the 29th dose (Cpre,ss,29).
Safety of BIBW 2992 as Indicated by Incidence of Specified Adverse Events. First administration of trial medication until 28 days after last administration of trial medication, up to 93 months. Safety of afatinib as indicated by incidence of specified adverse events: skin reactions (a preferred term of the system organ class: Skin and subcutaneous tissue disorders) and gastrointestinal (GI) (a system organ class).
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. Clinical benefit was evaluated according to RECIST 1.0 by independent review assessment. Patients whose best RECIST 1.0 assessment was stable disease (SD), partial response (PR), or complete response (CR) were considered to have derived a clinical benefit from treatment.
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 clinical benefit (disease control) as per independent review was defined as the time from the start of treatment to the time of progression or death (whichever occurred first), among patients with evidence of SD, PR or CR.
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. 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 (or date of censoring for PFS) was objectively documented as per independent review.
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. Time to objective response was defined as the number of days from the start of treatment to the first recorded objective response. Patients who did not experience objective response during the study were censored at the time of treatment discontinuation.
The results are provided as the percentage of participants for this Outcome Measure.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. Progression-free survival (PFS) as per independent review was defined as the duration of time from the start of treatment until the day of objective tumor progression was confirmed by tumor imaging (Progressive Disease according to RECIST 1.0) or death, whichever came first. Patients with unknown progression status or unknown date of progression were reviewed on a case-by-case basis. Patients known to be alive without progression at the end of the trial or the last follow-up visit were censored at the date of the last imaging when the patient was known to be alive and progression-free. Medians are calculated from the Kaplan-Meier estimates and 95% confidence intervals, using Greenwood's standard error estimate.
Overall Survival Time Start of treatment to time to all death, up to 93 months Overall survival time (OS) was also evaluated and was defined as the duration of time from start of treatment to time of death up to 93 months, regardless of the cause of death. Medians are calculated from the Kaplan-Meier estimates and 95% confidence intervals, using Greenwood's standard error estimate.
Safety of BIBW 2992 as Indicated by Intensity and Incidence of Worst Adverse Events Graded According to NCI CTCAE Version 3.0 First administration of trial medication until 28 days after last administration of trial medication, up to 93 months. Safety of afatinib as indicated by intensity and incidence of worst adverse events graded according to National Cancer Institute (NCI) Common terminology criteria for adverse events (CTCAE) Version 3.0 (R04-0474).
Trial Locations
- Locations (30)
1200.22.88602 Veterans General Hospital
🇨🇳Taipei, Taiwan
1200.22.88601 National Taiwan University Hospital
🇨🇳Taipei, Taiwan
1200.22.28 Boehringer Ingelheim Investigational Site
🇺🇸Bakersfield, California, United States
1200.22.19 Boehringer Ingelheim Investigational Site
🇺🇸Fort Lauderdale, Florida, United States
1200.22.18 Boehringer Ingelheim Investigational Site
🇺🇸Chicago, Illinois, United States
1200.22.27 Boehringer Ingelheim Investigational Site
🇺🇸Syracuse, New York, United States
1200.22.25 Boehringer Ingelheim Investigational Site
🇺🇸Valhalla, New York, United States
1200.22.6 Boehringer Ingelheim Investigational Site
🇺🇸Canton, Ohio, United States
1200.22.29 Boehringer Ingelheim Investigational Site
🇺🇸North Miami Beach, Florida, United States
1200.22.32 Boehringer Ingelheim Investigational Site
🇺🇸Beverly Hills, California, United States
1200.22.4 Boehringer Ingelheim Investigational Site
🇺🇸Mission Hills, California, United States
1200.22.88606 Boehringer Ingelheim Investigational Site
🇨🇳Tainan, Taiwan
1200.22.10 Boehringer Ingelheim Investigational Site
🇺🇸Atlanta, Georgia, United States
1200.22.26 Boehringer Ingelheim Investigational Site
🇺🇸New York, New York, United States
1200.22.5 Boehringer Ingelheim Investigational Site
🇺🇸Minneapolis, Minnesota, United States
1200.22.3 Boehringer Ingelheim Investigational Site
🇺🇸Bethesda, Maryland, United States
1200.22.16 Boehringer Ingelheim Investigational Site
🇺🇸Orange, California, United States
1200.22.14 Boehringer Ingelheim Investigational Site
🇺🇸Boston, Massachusetts, United States
1200.22.24 Boehringer Ingelheim Investigational Site
🇺🇸Flint, Michigan, United States
1200.22.1 Boehringer Ingelheim Investigational Site
🇺🇸Rochester, New York, United States
1200.22.15 Boehringer Ingelheim Investigational Site
🇺🇸New York, New York, United States
1200.22.7 Boehringer Ingelheim Investigational Site
🇺🇸Wynnewood, Pennsylvania, United States
1200.22.22 Boehringer Ingelheim Investigational Site
🇺🇸Mt. Pleasant, South Carolina, United States
1200.22.33 Boehringer Ingelheim Investigational Site
🇺🇸Seattle, Washington, United States
1200.22.88604 Taichung Veterans General Hospital
🇨🇳Taichung, Taiwan
1200.22.31 Boehringer Ingelheim Investigational Site
🇺🇸Fairfax, Virginia, United States
1200.22.40 Boehringer Ingelheim Investigational Site
🇺🇸Renton, Washington, United States
1200.22.88605 China Medical University Hospital
🇨🇳Taichung, Taiwan
1200.22.88607 Boehringer Ingelheim Investigational Site
🇨🇳Taipei City, Taiwan
1200.22.88603 Chang Gung Memorial Hosp-Linkou
🇨🇳Taoyuan, Taiwan