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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BIBW 2992 MA2 40mg/day | Drug | Phase I step: Increased dose cohorts from low dose to MTD |
| |
| Measure | Description | Time Frame |
|---|---|---|
| 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) | 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. | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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 |
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Inclusion criteria:
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.
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.
Exclusion criteria:
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.
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
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).
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| Name | Affiliation | Role |
|---|---|---|
| Boehringer Ingelheim | Boehringer Ingelheim | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| 1200.33.010 Boehringer Ingelheim Investigational Site | Akashi, Hyogo | Japan | ||||
| 1200.33.001 Boehringer Ingelheim Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23816963 | Derived | 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. | |
| 22071596 |
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| ID | Title | Description |
|---|---|---|
| FG000 | BIBW 20mg | Continuous once daily oral treatment with BIBW 2992 20mg tablets |
| FG001 | BIBW 40mg | Continuous once daily oral treatment with BIBW 2992 40mg tablets |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| BIBW 2992 MA2 50mg/day |
| Drug |
Phase I step: Increased dose cohorts from low dose to MTD |
|
| BIBW 2992 MA2 20mg/day | Drug | Phase I step: Increased dose cohorts from low dose to MTD |
|
| BIBW 2992 QD | Drug | Phase II step: This is an open label study. Patients are treated with BIBW 2992 until disease progression or undue AEs. |
|
| 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. | 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. | 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. | 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 | Screening visit |
| Phase II Step: Duration of Clinical Benefit | Presented as duration of disease control. | 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. | 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. | 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. | 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 | 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. | 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 | 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 | Course 2 Day 15 |
| 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 |
| Chuo-ku, Tokyo |
| Japan |
| 1200.33.007 Boehringer Ingelheim Investigational Site | Fukuoka, Fukuoka | Japan |
| 1200.33.013 Boehringer Ingelheim Investigational Site | Hidaka, Saitama | Japan |
| 1200.33.011 Boehringer Ingelheim Investigational Site | Kanazawa, Ishikawa | Japan |
| 1200.33.003 Boehringer Ingelheim Investigational Site | Kashiwa, Chiba | Japan |
| 1200.33.019 Boehringer Ingelheim Investigational Site | Kobe, Hyogo | Japan |
| 1200.33.008 Boehringer Ingelheim Investigational Site | Koto-ku, Tokyo | Japan |
| 1200.33.020 Boehringer Ingelheim Investigational Site | Matsuyama, Ehime | Japan |
| 1200.33.006 Boehringer Ingelheim Investigational Site | Miyakojima-ku, Osaka | Japan |
| 1200.33.004 Boehringer Ingelheim Investigational Site | Nagoya, Aichi | Japan |
| 1200.33.017 Boehringer Ingelheim Investigational Site | Nagoya, Aichi | Japan |
| 1200.33.016 Boehringer Ingelheim Investigational Site | Niigata, Niigata | Japan |
| 1200.33.009 Boehringer Ingelheim Investigational Site | Okayama, Okayama | Japan |
| 1200.33.005 Boehringer Ingelheim Investigational Site | Osaka-Sayama, Osaka | Japan |
| 1200.33.018 Boehringer Ingelheim Investigational Site | Sakai, Osaka | Japan |
| 1200.33.015 Boehringer Ingelheim Investigational Site | Sapporo, Hokkaido | Japan |
| 1200.33.012 Boehringer Ingelheim Investigational Site | Sendai, Miyagi | Japan |
| 1200.33.002 Boehringer Ingelheim Investigational Site | Sunto-gun, Shizuoka | Japan |
| 1200.33.014 Boehringer Ingelheim Investigational Site | Yufu, Oita | Japan |
| Derived |
| 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. |
| FG002 | BIBW 50mg (Phase I) | Continuous once daily oral treatment with BIBW 2992 50mg tablets |
| FG003 | BIBW 50mg (Phase II) | Continuous once daily oral treatment with BIBW 2992 50mg tablets |
| COMPLETED |
|
| NOT COMPLETED |
|
|
Until the snapshot for CTR
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| ID | Title | Description |
|---|---|---|
| BG000 | BIBW 20mg | Continuous once daily oral treatment with BIBW 2992 20mg tablets |
| BG001 | BIBW 40mg | Continuous once daily oral treatment with BIBW 2992 40mg tablets |
| BG002 | BIBW 50mg (Phase I) | Continuous once daily oral treatment with BIBW 2992 50mg tablets |
| BG003 | BIBW 50mg (Phase II) | Continuous once daily oral treatment with BIBW 2992 50mg tablets |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | BIBW 20mg, 40mg, 50mg (Phase I) | Median | Full Range | years |
| ||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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 | The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication. | Posted | Number | participants | start of treatment to end of treatment |
|
|
| |||||||||||||||||||||||||||||||||||
| Primary | 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. | 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. | Posted | Number | 95% Confidence Interval | percentage of participants | 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 | 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. | "Treated set" was defined as all patients who received at least 1 dose of BIBW2992. Some samples were excluded from calculation of descriptive statistics of plasma concentration because these were taken outside the allowed time-windows but used for calculation of PK parameters. Number of analyzed patients of BIBW 50mg:5(AUCtau,ss), 40mg:2(AUC0-24) | Posted | Geometric Mean | Geometric Coefficient of Variation | ng·h/mL | 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 |
| |||||||||||||||||||||||||||||||||||
| Secondary | 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. | The "full analysis set" of patients was defined as all patients includes in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started. | Posted | Number | 95% Confidence Interval | percentage of participants | 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 | 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. | The "full analysis set" of patients was defined as all patients includes in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started. | Posted | Number | Number of patients | 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 | 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. | The "full analysis set" of patients was defined as all patients includes in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started. | Posted | Median | Full Range | weeks | 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 | Phase I Step: Summary of Epidermal Growth Factor Receptor (EGFR) Mutation Findings | The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication. | Posted | Number | participants | Screening visit |
|
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| Secondary | Phase II Step: Duration of Clinical Benefit | Presented as duration of disease control. | The "full analysis set" of patients was defined as all patients includes in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started. | Posted | Median | Full Range | Weeks | 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 | 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. | The "full analysis set" of patients was defined as all patients includes in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started. | Posted | Median | Inter-Quartile Range | Months | 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 |
|
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| Secondary | Phase II Step: Overall Survival (OS) | OS was defined as the duration of time from the start of treatment to the time of death. | The "full analysis set" of patients was defined as all patients includes in the treated set who have both baseline tumour imaging data and at least one analysable tumour imaging data after BIBW 2992 started. | Posted | Median | Inter-Quartile Range | Months | from start of treatment until end of follow up, up to 53 months |
|
| ||||||||||||||||||||||||||||||||||
| Secondary | 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. | The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication. | Posted | Number | participants | Start of treatment to end of treatment (up to 41.3 months) plus 4 week follow-up |
|
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| Secondary | 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 | The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication. For activated partial thromboplastin time (APTT), N = 59 For Prothrombin Time and International Normalized Ratio (PT-INR), N = 61 | Posted | Number | participants | Start of treatment to end of treatment (up to 41.3 months) plus 4 week follow-up |
|
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| Secondary | 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. | Plasma concentrations of BIBW2992 were to be presented for all patients and sampling points with concentrations above the lower limit of quantification. No patient was treated with 30 mg during the Course 1. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/ml | Course 1 Day 15 |
| |||||||||||||||||||||||||||||||||||
| Secondary | 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 | Plasma concentrations of BIBW2992 were to be presented for all patients and sampling points with concentrations above the lower limit of quantification. 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/ml | Course 2 Day 1 |
| |||||||||||||||||||||||||||||||||||
| Secondary | 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 | Plasma concentrations of BIBW2992 were to be presented for all patients and sampling points with concentrations above the lower limit of quantification. 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. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/ml | Course 2 Day 15 |
| |||||||||||||||||||||||||||||||||||
| Secondary | Phase II Step: Summary of EGFR Mutation Findings | The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication. | Posted | Number | participants | Screening visit |
|
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| |||||||||||||||||||||||||||||||||||
| Secondary | Phase I Step: Cmax,Cmax,ss of BIBW 2992 After Multiple Oral Administration | The "treated set" of patients was defined as all patients who received at least 1 dose of BIBW 2992 medication.Some samples were excluded from the evaluation because these were taken outside the allowed time-windows. Number of analyzed patients of BIBW 50mg cohort for Cmax,ss: 5 | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Just before start of the treatment to Course 4 Visit 4R2 |
|
|
from first administration of study medication up to 28 days after the completion of drug administration, up to 1260 days
Not provided
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BIBW 20mg | Continuous once daily oral treatment with BIBW 2992 20mg tablets | 1 | 3 | 3 | 3 | ||
| EG001 | BIBW 40mg | Continuous once daily oral treatment with BIBW 2992 40mg tablets | 0 | 3 | 3 | 3 | ||
| EG002 | BIBW 50mg (Phase I) | Continuous once daily oral treatment with BIBW 2992 50mg tablets | 2 | 6 | 6 | 6 | ||
| EG003 | BIBW 50mg (Phase II) | Continuous once daily oral treatment with BIBW 2992 50mg tablets | 16 | 62 | 62 | 62 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bronchitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Pneumonia bacterial | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Bile duct cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Metastatic pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MEDDRA 16.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Ileus | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Spinal osteoarthritis | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Renal failure acute | Renal and urinary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Bone contusion | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Neutropenia | Blood and lymphatic system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Conjunctivitis | Eye disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Epidermolysis | Congenital, familial and genetic disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cheilitis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Gingivitis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Glossitis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pancreatitis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Peritonitis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cholangitis | Hepatobiliary disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Gait disturbance | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Malaise | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Mucosal dryness | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Mucosal inflammation | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Tenderness | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Thirst | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Vessel puncture site haematoma | General disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Cystitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MEDDRA 16.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Blood albumin decreased | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Blood urine present | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Haemoglobin decreased | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Protein total decreased | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| White blood cells urine positive | Investigations | MEDDRA 16.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Gout | Metabolism and nutrition disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dysgeusia | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dysphonia | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Nasal inflammation | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Oropharyngeal discomfort | Respiratory, thoracic and mediastinal disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Acne | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Nail disorder | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Skin fissures | Skin and subcutaneous tissue disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Haemorrhage | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MEDDRA 16.1 | Systematic Assessment |
| |
| Excoriation | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MEDDRA 16.1 | Systematic Assessment |
|
Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Boehringer Ingelheim Call Center | Boehringer Ingelheim Pharmaceuticals | 1-800-243-0127 | clintriage.rdg@boehringer-ingelheim.com |
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D000077716 | Afatinib |
| ID | Term |
|---|---|
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D011799 | Quinazolines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
Not provided
| Male |
|
|
| Other significant AEs (according to ICH E3) |
|
| AEs leading to discontinuation of trial drug |
|
| Serious AEs |
|
| SAE: Requiring hospitalisation |
|
| SAE: Prolonging hospitalisation |
|
| SAE: Other |
|
| Highest CTCAE grade for AEs (Grade 1) |
|
| Highest CTCAE grade for AEs (Grade 2) |
|
| Highest CTCAE grade for AEs (Grade 3) |
|
| Highest CTCAE grade for AEs (Grade 4) |
|
| Highest CTCAE grade for AEs (Grade 5) |
|
| Patients with any DLT (Course 1) |
|
| Patients with any DLT (All Courses) |
|
|
Continuous once daily oral treatment with BIBW 2992 50mg tablets
|
|
|
|
|
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| Categories |
|---|
| EGFR Mutation test done (local or central) |
| |||||
| Positive |
| |||||
| Del19 |
| |||||
| Del19 + L858R |
| |||||
| Del19 + T790M |
| |||||
| Del19 + Other |
| |||||
| L858R |
| |||||
| L858R + T790M |
| |||||
| L858R + Other |
| |||||
| L861Q |
| |||||
| Negative |
|
|