Carcinoma, Non-Small-Cell LungPhase 2NCT00711594

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

A Phase 2 study testing BIBW 2992 MA2 40mg/day, BIBW 2992 MA2 50mg/day and BIBW 2992 MA2 20mg/day in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 20 sites in Japan.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial 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. Read more about this study

Who is it for?: Ages 20 years and older
Conditions the study is for: Carcinoma, Non-Small-Cell Lung
What is being tested?: BIBW 2992 MA2 40mg/day, BIBW 2992 MA2 50mg/day and BIBW 2992 MA2 20mg/day
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 74 participants
Where: 20 sitesJapan
Study dates: Apr 2008to Nov 2013
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 20 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Phase II step;
Patients with pathologic confirmation of NSCLC with tissue diagnosis or cytologic diagnosis, whose NSCLCs are locally advanced or metastatic Stage III-B / IV adenocarcinoma, and are inoperable and incurable with radiotherapy.
Patients who have received the following pretreatments for the treatment of relapsed or metastatic NSCLC.
Patients who have received at least one but not more than two lines of chemotherapy. ("Chemotherapy" means only the first line (doublet chemotherapies including a platinum) and/or the second line (single chemotherapy except for a platinum) of cytotoxic chemotherapy according to the standard chemotherapies, and erlotinib (Tarceva®) and gefitinib (Iressa®) should be excluded. One of the chemotherapy regimens must have been platinum-based. In addition, only one prior cytotoxic chemotherapy treatment regimen is allowed after adjuvant chemotherapy containing a platinum. More than two prior cytotoxic chemotherapy treatment regimens are not allowed.)
After the above chemotherapies, patients who once got clinical benefits (i.e. complete response, partial response or stable disease) but progressed following at least 12 weeks of treatment with erlotinib (Tarceva®) or gefitinib (Iressa®) as the most recent treatment. ("Clinical benefit" and "progression" should be confirmed by computed tomography (CT) or magnetic resonance imaging (MRI). In addition, "at least 12 weeks of treatment" should be 9 weeks or more as the actual "treatment period except for treatment pause due to adverse events and other reasons.) As long as the treatment is erlotinib or gefitinib monotherapy, patients can receive multiple regimens of either or both treatments, but one of the regimens should be for at least 12 weeks
Male or female patients age >=20 years at the enrolment.

Show all 10Show fewer

Life expectancy of at least three (3) months after the start of administration of the investigational drug.
Eastern Cooperative Oncology Group (ECOG) performance Score 0 or 1.
Patients with at least one tumor lesion that can accurately be measured by CT or MRI in at least one dimension with longest diameter to be recorded as no less than double the slice thickness and >=10 mm.
Written informed consent that is consistent with ICH-GCP guidelines.

Who cannot join

Phase II step;
Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within two weeks before starting the study medication.
Patients who have received definitive thoracic radiotherapy with curative intent. Patients who have received radiotherapy or other investigational drugs (non-oncological) within four weeks before enrolment.
Significant gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn's disease, mal-absorption, or CTCAE Grade >2 diarrhea of any etiology at the enrolment.
Patients with distinct / suspected pulmonary fibrosis or interstitial lung disease by the chest radiographic findings, or patients with a previous history of.
Brain tumor, and / or brain metastases, which are symptomatic or requiring treatment at the enrolment.

Show all 26Show fewer

Other malignancies diagnosed within the past five years (other than carcinoma in situ of gastric cancer, colon cancer and cervical cancer, and non melanomatous skin cancer).
History of uncontrolled cardiac disease such as angina or myocardial infarction within the past 6 months at the enrolment, congestive heart failure including New York Heart Association (NYHA) functional classification of 3, or arrhythmia requiring treatment.
Coelomic fluid retention (such as pleural effusion, ascites or pericardial effusion) requiring treatment.
Uncontrolled concomitant diseases (e.g. diabetes mellitus, hypertension etc).
History of serious drug hypersensitivity.
Patients who do not have sufficient baseline organ function and whose laboratory data do not meet the following criteria at the enrolment.11
Haemoglobin count >=9.0 g/dL
Absolute neutrophil count (ANC) >=1500 / mm3
Platelet count >=100 000 / mm3
Serum creatinine <=1.5 mg/dL
Total bilirubin <=1.5 mg/dL
Aspartate aminotransferase (AST) and / or alanine aminotransferase (ALT) <=2.5x upper limit of normal range (if related to liver metastases <=2.5x upper limit of normal also)
PaO2 >=60torr or SpO2 >=92%
LVEF as measured by echocardiography or multigated blood pool imaging of the heart (MUGA scan) >=50%
QTc interval <0.47 second
Patients who disagree with using a medically acceptable method of contraception during the administration of the investigational drug and for at least 6 months after the end of administration.
Pregnant or breast-feeding women, or women suspected of being pregnant.
Known positive HBs antigen, HCV antibody, or HIV antibody test.
Known or suspected active drug or alcohol abuse.
Other patients judged ineligible for enrolment in the study by the investigator (sub-investigator).

Trial locations and contacts

20 sites in 1 country.

City, postcode or hospital

20 sites in 1 country

Japan20 sites

1200.33.010 Boehringer Ingelheim Investigational Site
Akashi, Hyogo
1200.33.001 Boehringer Ingelheim Investigational Site
Chuo-ku, Tokyo
1200.33.007 Boehringer Ingelheim Investigational Site
Fukuoka, Fukuoka
1200.33.013 Boehringer Ingelheim Investigational Site
Hidaka, Saitama
1200.33.011 Boehringer Ingelheim Investigational Site
Kanazawa, Ishikawa
1200.33.003 Boehringer Ingelheim Investigational Site
Kashiwa, Chiba
1200.33.019 Boehringer Ingelheim Investigational Site
Kobe, Hyogo
1200.33.008 Boehringer Ingelheim Investigational Site
Koto-ku, Tokyo
1200.33.020 Boehringer Ingelheim Investigational Site
Matsuyama, Ehime
1200.33.006 Boehringer Ingelheim Investigational Site
Miyakojima-ku, Osaka
1200.33.004 Boehringer Ingelheim Investigational Site
Nagoya, Aichi
1200.33.017 Boehringer Ingelheim Investigational Site
Nagoya, Aichi
1200.33.016 Boehringer Ingelheim Investigational Site
Niigata, Niigata
1200.33.009 Boehringer Ingelheim Investigational Site
Okayama, Okayama
1200.33.005 Boehringer Ingelheim Investigational Site
Osaka-Sayama, Osaka
1200.33.018 Boehringer Ingelheim Investigational Site
Sakai, Osaka
1200.33.015 Boehringer Ingelheim Investigational Site
Sapporo, Hokkaido
1200.33.012 Boehringer Ingelheim Investigational Site
Sendai, Miyagi
1200.33.002 Boehringer Ingelheim Investigational Site
Sunto-gun, Shizuoka
1200.33.014 Boehringer Ingelheim Investigational Site
Yufu, Oita

Other trials in Japan

About this study

Official title: Phase I/II Open Label Trial of Continuous Once Daily Oral Treatment With BIBW 2992 - 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.

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.

Conditions: Carcinoma, Non-Small-Cell Lung
Being tested: BIBW 2992 MA2 40mg/day, BIBW 2992 MA2 50mg/day, BIBW 2992 MA2 20mg/day, BIBW 2992 QD
Medical subject headings: Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

BIBW 2992 MA2 40mg/dayDrug
Phase I step: Increased dose cohorts from low dose to MTD
BIBW 2992 MA2 50mg/dayDrug
Phase I step: Increased dose cohorts from low dose to MTD
BIBW 2992 MA2 20mg/dayDrug
Phase I step: Increased dose cohorts from low dose to MTD
BIBW 2992 QDDrug
Phase II step: This is an open label study. Patients are treated with BIBW 2992 until disease progression or undue AEs.

Study groups in NCT00711594
Study group	Role	What they receive
BIBW 2992 MA2	Experimental	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. Receives: Drug: BIBW 2992 MA2 40mg/day; Drug: BIBW 2992 MA2 50mg/day; Drug: BIBW 2992 MA2 20mg/day
BIBW 2992 QD	Experimental	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. Receives: Drug: BIBW 2992 QD

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: start of treatment to end of treatment
Phase II Step: Objective Tumour Response According to Response Evaluation Criteria in Solid Tumours (RECIST)
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.
Measured: 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

Secondary outcomes (15)

Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration
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.
Measured: 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
Phase II Step: Clinical Benefit
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.
Measured: 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
Phase II Step: Time to Objective Response
Number of participants with first response at week 4, 8 and 12, assessed by investigator and independent review.
Measured: 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
Phase II Step: Duration of Objective Response
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.
Measured: 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
Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings
Measured: Screening visit
Phase II Step: Duration of Clinical Benefit
Presented as duration of disease control.
Measured: 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
Phase II Step: Progression-free Survival (PFS)
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.
Measured: 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
Phase II Step: Overall Survival (OS)
OS was defined as the duration of time from the start of treatment to the time of death.
Measured: from start of treatment until end of follow up, up to 53 months
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE
outcome data show the number of patients with Adverse events (AE) by intensity and incidence of adverse events, graded according to CTCAE.
Measured: Start of treatment to end of treatment (up to 41.3 months) plus 4 week follow-up
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline
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
Measured: Start of treatment to end of treatment (up to 41.3 months) plus 4 week follow-up
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course1 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.
Measured: Course 1 Day 15
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 1
Outcome data show the gMean of trough plasma concentrations of BIBW 2992 after multiple oral administration of BIBW
Measured: Course 2 Day 1
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 15
Outcome data show the gMean of trough plasma concentrations of BIBW 2992 after multiple oral administration of BIBW
Measured: Course 2 Day 15
Phase II Step: Summary of EGFR Mutation Findings
Measured: Screening visit
Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration
Measured: Just before start of the treatment to Course 4 Visit 4R2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2008Nov 2013

First posted9 Jul 2008 (estimated)
Study startApr 2008
Primary completionNov 2013
Study completionNov 2013

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Enrolment: 74 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00711594
Sponsor's protocol ID: 1200.33
Status last verified: Jan 2015
First submitted: 8 Jul 2008
Last updated: 15 Jan 2015
Results posted: Yes, on ClinicalTrials.gov

Publications

Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol. 2013 Sep 20;31(27):3335-41. doi: 10.1200/JCO.2012.45.0981. Epub 2013 Jul 1.
PubMed 23816963
Murakami H, Tamura T, Takahashi T, Nokihara H, Naito T, Nakamura Y, Nishio K, Seki Y, Sarashina A, Shahidi M, Yamamoto N. Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4). Cancer Chemother Pharmacol. 2012 Apr;69(4):891-9. doi: 10.1007/s00280-011-1738-1. Epub 2011 Nov 10.
PubMed 22071596

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 15 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I/II Open Label Trial of Continuous Once Daily Oral Treatment With BIBW 2992 - 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.
ClinicalTrials.gov ID: NCT00711594
Acronym / sponsor ID: 1200.33
Conditions: Carcinoma, Non-Small-Cell Lung
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 74 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: Apr 2008
Primary completion: Nov 2013 (actual)
Study completion: Nov 2013 (actual)
First posted: 9 Jul 2008 (estimated)
Results: Posted 13 Nov 2013

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Single group
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
BIBW 2992 MA2	Experimental	Drug: BIBW 2992 MA2 40mg/day, Drug: BIBW 2992 MA2 50mg/day, Drug: BIBW 2992 MA2 20mg/dayPhase 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	Experimental	Drug: BIBW 2992 QDPhase 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.

Who may qualify

Ages: 20 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Phase II step;
Patients with pathologic confirmation of NSCLC with tissue diagnosis or cytologic diagnosis, whose NSCLCs are locally advanced or metastatic Stage III-B / IV adenocarcinoma, and are inoperable and incurable with radiotherapy.
Patients who have received the following pretreatments for the treatment of relapsed or metastatic NSCLC.
Male or female patients age >=20 years at the enrolment.
Life expectancy of at least three (3) months after the start of administration of the investigational drug.

Key exclusion criteria (26 listed)

Phase II step;
Use of erlotinib (Tarceva®) or gefitinib (Iressa®) within two weeks before starting the study medication.
Patients who have received definitive thoracic radiotherapy with curative intent. Patients who have received radiotherapy or other investigational drugs (non-oncological) within four weeks before enrolment.
Significant gastrointestinal disorders with diarrhea as a major symptom e.g., Crohn's disease, mal-absorption, or CTCAE Grade >2 diarrhea of any etiology at the enrolment.
Patients with distinct / suspected pulmonary fibrosis or interstitial lung disease by the chest radiographic findings, or patients with a previous history of.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BIBW 2992 MA2 40mg/dayPhase I step: Increased dose cohorts from low dose to MTD	Drug	BIBW 2992 MA2
BIBW 2992 MA2 50mg/dayPhase I step: Increased dose cohorts from low dose to MTD	Drug	BIBW 2992 MA2
BIBW 2992 MA2 20mg/dayPhase I step: Increased dose cohorts from low dose to MTD	Drug	BIBW 2992 MA2
BIBW 2992 QDPhase II step: This is an open label study. Patients are treated with BIBW 2992 until disease progression or undue AEs.	Drug	BIBW 2992 QD

Primary outcome

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
Time frame: start of treatment to end of treatment
Phase II Step: Objective Tumour Response According to Response Evaluation Criteria in Solid Tumours (RECIST)
Time frame: 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.

15 secondary outcomes

Phase I Step: AUC0-24, AUCtau,ss of BIBW 2992 After Multiple Oral Administration
Time frame: 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
Phase II Step: Clinical Benefit
Time frame: 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
Phase II Step: Time to Objective Response
Time frame: 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
Phase II Step: Duration of Objective Response
Time frame: 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
Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings
Time frame: Screening visit
Phase II Step: Duration of Clinical Benefit
Time frame: 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
Phase II Step: Progression-free Survival (PFS)
Time frame: 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
Phase II Step: Overall Survival (OS)
Time frame: from start of treatment until end of follow up, up to 53 months
Phase II Step: Safety of BIBW 2992 as Indicated by Intensity and Incidence of Adverse Events, Graded According to CTCAE
Time frame: Start of treatment to end of treatment (up to 41.3 months) plus 4 week follow-up
Phase II Step: Maximum CTC Grade During the Trial for Laboratory Parameters, Among Patients Who Experienced an Increase in CTC Grade From Baseline
Time frame: Start of treatment to end of treatment (up to 41.3 months) plus 4 week follow-up
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course1 Day 15
Time frame: Course 1 Day 15
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 1
Time frame: Course 2 Day 1
Phase II Step: Trough Plasma Concentrations of BIBW2992 After Multiple Oral Administration of BIBW 2992: Treatment course2 Day 15
Time frame: Course 2 Day 15
Phase II Step: Summary of EGFR Mutation Findings
Time frame: Screening visit
Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration
Time frame: Just before start of the treatment to Course 4 Visit 4R2

Results and safety

Results posted to the registry on 13 Nov 2013, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
BIBW 20mg	3	0
BIBW 40mg	3	0
BIBW 50mg (Phase I)	6	0
BIBW 50mg (Phase II)	62	0

Primary outcome: 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

Time frame: start of treatment to end of treatment. Number. Unit: participants

Measure	BIBW 20mg n = 3	BIBW 40mg n = 3	BIBW 50mg (Phase I) n = 6
Patients with any AE	3	3	6
Investigator defined drug-related AEs	3	3	6
Other significant AEs (according to ICH E3)	0	1	1
AEs leading to discontinuation of trial drug	1	0	0
Serious AEs	1	0	2
SAE: Requiring hospitalisation	0	0	1
SAE: Prolonging hospitalisation	1	0	1
SAE: Other	1	0	0

Population analysed: The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication.

Primary outcome: Phase II Step: Objective Tumour Response According to Response Evaluation Criteria in Solid Tumours (RECIST)

Time frame: 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 (95% Confidence Interval). Unit: percentage of participants

Measure	BIBW 50mg (Phase II) n = 61
Independent review	8.2 (2.7 to 18.1)
Investigator assessment	13.1 (5.8 to 24.2)

Population analysed: The "full analysis set" of patients was defined as all patients included in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started.

15 secondary outcomes are reported in the full results.

Adverse events

Time frame: from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
BIBW 20mg	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
BIBW 40mg	0 of 3 (0%)	3 of 3 (100%)	Not reported
BIBW 50mg (Phase I)	2 of 6 (33.3%)	6 of 6 (100%)	Not reported
BIBW 50mg (Phase II)	16 of 62 (25.8%)	62 of 62 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 23816963Katakami N, Atagi S, Goto K, Hida T, Horai T, Inoue A, Ichinose Y, Koboyashi K, Takeda K, Kiura K, Nishio K, Seki Y, Ebisawa R, Shahidi M, Yamamoto N. LUX-Lung 4: a phase II trial of afatinib in patients with advanced non-small-cell lung cancer who progressed during prior treatment with erlotinib, gefitinib, or both. J Clin Oncol. 2013 Sep 20;31(27):3335-41. doi: 10.1200/JCO.2012.45.0981. Epub 2013 Jul 1.
Derived from this study: PubMed 22071596Murakami H, Tamura T, Takahashi T, Nokihara H, Naito T, Nakamura Y, Nishio K, Seki Y, Sarashina A, Shahidi M, Yamamoto N. Phase I study of continuous afatinib (BIBW 2992) in patients with advanced non-small cell lung cancer after prior chemotherapy/erlotinib/gefitinib (LUX-Lung 4). Cancer Chemother Pharmacol. 2012 Apr;69(4):891-9. doi: 10.1007/s00280-011-1738-1. Epub 2011 Nov 10.
Related InfoLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Boehringer Ingelheim study chair

Boehringer Ingelheim

20 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing BIBW 2992 MA2 40mg/day, BIBW 2992 MA2 50mg/day and BIBW 2992 MA2 20mg/day in people with Carcinoma, Non-Small-Cell Lung, run by Boehringer Ingelheim at 20 sites in Japan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 13 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: start of treatment to end of treatment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00711594, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jan 2015.