LUX-Lung 4: BIBW 2992 (Afatinib) Phase I Trial in Advanced Non Small Cell Lung Cancer Patients & Phase II Trial in Non Small Cell Lung Cancer Patients Failing Erlotinib or Gefitinib

Phase 2

Completed

• Conditions: Carcinoma, Non-Small-Cell Lung
• Interventions: Drug: BIBW 2992 MA2 40mg/day; Drug: BIBW 2992 QD; Drug: BIBW 2992 MA2 50mg/day; Drug: BIBW 2992 MA2 20mg/day

• Registration Number: NCT00711594
• Lead Sponsor: Boehringer Ingelheim

Brief Summary

The objective of the Phase I step is to estimate the MTD at a dose level up to 50 mg/day (i.e., overseas recommended Phase II dose) in patients with advanced NSCLC and to determine the recommended dose for the Phase II step.

The objective of the Phase II step is to estimate the efficacy of BIBW 2992 monotherapy in patients with first generation EGFR-TKI-resistant advanced NSCLC at the recommended dose determined in the Phase I step.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2008-04
• Study First Submitted: 2008-07-08
• Study First Submitted QC: 2008-07-08
• Study First Posted: 2008-07-09
• Results First Submitted: 2013-08-08
• Results First Submitted QC: 2013-10-21
• Primary Completion: 2013-11
• Study Completion: 2013-11
• Results First Posted: 2013-11-13
• Status Verified: 2015-01
• Last Update Submitted: 2015-01-13
• Last Update Posted: 2015-01-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 74

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BIBW 2992 MA2	BIBW 2992 MA2 40mg/day	Phase I step: Find maximum tolerated dose of the non-marketed substance:BIBW 2992 given orally. Escalating doses of BIBW 2992 starting at 20mg daily.
BIBW 2992 MA2	BIBW 2992 MA2 50mg/day	Phase I step: Find maximum tolerated dose of the non-marketed substance:BIBW 2992 given orally. Escalating doses of BIBW 2992 starting at 20mg daily.
BIBW 2992 MA2	BIBW 2992 MA2 20mg/day	Phase I step: Find maximum tolerated dose of the non-marketed substance:BIBW 2992 given orally. Escalating doses of BIBW 2992 starting at 20mg daily.
BIBW 2992 QD	BIBW 2992 QD	Phase II step: 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.

Primary Outcome Measures

Name	Time	Method
Phase I Step: Safety of BIBW 2992 Assessed Based on Incidence of Dose Limiting Toxicity (DLT) and Incidence & Intensity of Adverse Events According to CTCAE	start of treatment to end of treatment
Phase II Step: Objective Tumour Response According to Response Evaluation Criteria in Solid Tumours (RECIST)	Tumour Assessment were performed at screening 14 days (prior to enrollment), in week 4, week 8, week 12 and in 8-week intervals thereafter, and at the end of trial visit (patients discontinuation), up to 41.3 months	The objective response (complete response \[CR\] and partial response \[PR\]) was defined as determined by the RECIST according to the best response to study treatment.

Secondary Outcome Measures

Name	Time	Method
Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration	AUC0-24: just before drug administration, 0:30,1:00, 2:00, 3:00, 4:00, 5:00, 7:00, 9:00, 24:00 on Day 1-2 in Course 1; AUCtau,ss: just before drug administration, 0:30,1:00, 2:00, 3:00, 4:00, 5:00, 7:00, 9:00, 24:00, 48:00, 72:00 on Day 28-31 in Course 1	area under the concentration-time curve of BIBW 2992 over the time interval 0-24 hours (AUC0-24), Area under the concentration-time curve of Afatinib in plasma at steady state (AUCtau,ss) after multiple oral administration Pharmacokinetic was abbreviated to PK.
Phase II Step: Clinical Benefit	Tumour Assessment were performed at screening 14 days (prior to enrollment), in week 4, week 8, week 12 and in 8-week intervals thereafter, and at the end of trial visit (patients discontinuation) up to 41.3 months	Clinical benefit was defined as a RECIST assessment of complete response, partial response, or stable disease according to the best response to study treatment as defined in the previous section. Clinical benefit presented as the disease control.
Phase II Step: Time to Objective Response	Tumour Assessment were performed at screening 14 days (prior to enrollment), in week 4, week 8, week 12 and in 8-week intervals thereafter, and at the end of trial visit (patients discontinuation) up to 41.3 months	Number of participants with first response at week 4, 8 and 12, assessed by investigator and independent review.
Phase II Step: Duration of Objective Response	Tumour Assessment were performed at screening 14 days (prior to enrollment), in week 4, week 8, week 12 and in 8-week intervals thereafter, and at the end of trial visit (patients discontinuation) up to 41.3 months	Duration of objective response was defined as the time at which RECIST was first met for CR or PR (whichever was first recorded) until the first date that recurrent or progressive disease (PD) was objectively documented.
Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings	Screening visit
Phase II Step: Duration of Clinical Benefit	Tumour Assessment were performed at screening 14 days (prior to enrollment), in week 4, week 8, week 12 and in 8-week intervals thereafter, and at the end of trial visit (patients discontinuation) up to 41.3 months	Presented as duration of disease control.
Phase II Step: Progression-free Survival (PFS)	Tumour Assessment were performed at screening 14 days (prior to enrollment), in week 4, week 8, week 12 and in 8-week intervals thereafter, and at the end of trial visit (patients discontinuation) up to 41.3 months	PFS was defined as the duration of time from the start of treatment until the day of objective tumour progression confirmed by tumour imaging (PD according to the RECIST) or death.
Phase II Step: Overall Survival (OS)	from start of treatment until end of follow up, up to 53 months	OS was defined as the duration of time from the start of treatment to the time of death.
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE	Start of treatment to end of treatment (up to 41.3 months) plus 4 week follow-up	outcome data show the number of patients with Adverse events (AE) by intensity and incidence of adverse events, graded according to CTCAE.
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline	Start of treatment to end of treatment (up to 41.3 months) plus 4 week follow-up	outcome data show the number of patients for the maximum CTC grade during the trial for laboratory parameters, among patients who experienced an increase in CTC Grade
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course1 Day 15	Course 1 Day 15	Outcome data show the geometric mean (gMean) of trough plasma concentrations of BIBW 2992 after multiple oral administration of BIBW.; The dose determined from the result of the Phase I step (50 mg) will be used. Reduction of dose in accordance to the criteria specified by adverse events to 40 mg or 30 mg was possible.
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 1	Course 2 Day 1	Outcome data show the gMean of trough plasma concentrations of BIBW 2992 after multiple oral administration of BIBW
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 15	Course 2 Day 15	Outcome data show the gMean of trough plasma concentrations of BIBW 2992 after multiple oral administration of BIBW
Phase II Step: Summary of EGFR Mutation Findings	Screening visit
Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration	Just before start of the treatment to Course 4 Visit 4R2

Trial Locations

Locations (20)

1200.33.006 Boehringer Ingelheim Investigational Site; 🇯🇵 Miyakojima-ku, Osaka, Japan

1200.33.010 Boehringer Ingelheim Investigational Site; 🇯🇵 Akashi, Hyogo, Japan

1200.33.003 Boehringer Ingelheim Investigational Site; 🇯🇵 Kashiwa, Chiba, Japan

1200.33.011 Boehringer Ingelheim Investigational Site; 🇯🇵 Kanazawa, Ishikawa, Japan

1200.33.007 Boehringer Ingelheim Investigational Site; 🇯🇵 Fukuoka, Fukuoka, Japan

1200.33.002 Boehringer Ingelheim Investigational Site; 🇯🇵 Sunto-gun, Shizuoka, Japan

1200.33.012 Boehringer Ingelheim Investigational Site; 🇯🇵 Sendai, Miyagi, Japan

1200.33.015 Boehringer Ingelheim Investigational Site; 🇯🇵 Sapporo, Hokkaido, Japan

1200.33.013 Boehringer Ingelheim Investigational Site; 🇯🇵 Hidaka, Saitama, Japan

1200.33.001 Boehringer Ingelheim Investigational Site; 🇯🇵 Chuo-ku, Tokyo, Japan

1200.33.008 Boehringer Ingelheim Investigational Site; 🇯🇵 Koto-ku, Tokyo, Japan

1200.33.020 Boehringer Ingelheim Investigational Site; 🇯🇵 Matsuyama, Ehime, Japan

1200.33.016 Boehringer Ingelheim Investigational Site; 🇯🇵 Niigata, Niigata, Japan

1200.33.018 Boehringer Ingelheim Investigational Site; 🇯🇵 Sakai, Osaka, Japan

1200.33.004 Boehringer Ingelheim Investigational Site; 🇯🇵 Nagoya, Aichi, Japan

1200.33.005 Boehringer Ingelheim Investigational Site; 🇯🇵 Osaka-Sayama, Osaka, Japan

1200.33.014 Boehringer Ingelheim Investigational Site; 🇯🇵 Yufu, Oita, Japan

1200.33.019 Boehringer Ingelheim Investigational Site; 🇯🇵 Kobe, Hyogo, Japan

1200.33.017 Boehringer Ingelheim Investigational Site; 🇯🇵 Nagoya, Aichi, Japan

1200.33.009 Boehringer Ingelheim Investigational Site; 🇯🇵 Okayama, Okayama, Japan