A Phase 2 interventional study of BIBW 2992 in Carcinoma, Non-Small-Cell Lung, sponsored by Boehringer Ingelheim. Completed at 30 sites in 2 countries. Open to participants aged 18 Years to 99 Years. Per ClinicalTrials.gov, last updated 2016-09-16.
Sponsored by Boehringer Ingelheim · Phase 2, Interventional, and Treatment
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.
6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.
This study's enrollment of 129 is above the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Browse Carcinoma, Non-Small-Cell Lung studies →Boehringer Ingelheim is the lead sponsor of 2,245 studies on the registry; 58 are open to participants now.
Of its 162 completed or terminated interventional studies of FDA-regulated products, 116 (72%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion criteria:
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
This is an open label study. Patients are treated with BIBW 2992 until disease progression or undue AEs
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.
Time frame: 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 as Determined by RECIST 1.0
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.
Time frame: 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
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.
Time frame: 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
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 frame: 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
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.
Time frame: 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
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.
Time frame: 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.
Overall Survival Time
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.
Time frame: Start of treatment to time to all death, up to 93 months
Cpre,ss,29
Predose concentration of the analyte in plasma at steady state immediately before administration of the 29th dose (Cpre,ss,29).
Time frame: -0:05h (pre-dose) on Day 29
Safety of BIBW 2992 as Indicated by Incidence of Specified Adverse Events.
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).
Time frame: First administration of trial medication until 28 days after last administration of trial medication, up to 93 months.
Safety of BIBW 2992 as Indicated by Intensity and Incidence of Worst Adverse Events Graded According to NCI CTCAE Version 3.0
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).
Time frame: First administration of trial medication until 28 days after last administration of trial medication, up to 93 months.
| Milestone | First-line Afatinib 40 mg | First-line Afatinib 50 mg | Second-line Afatinib 40 mg | Second-line Afatinib 50 mg |
|---|---|---|---|---|
| Started | 23 | 38 | 7 | 61 |
| Completed | 0 | 0 | 0 | 0 |
| Not completed | 23 | 38 | 7 | 61 |
| Withdrew: Other adverse event | 3 | 5 | 1 | 8 |
| Withdrew: Progressive disease | 18 | 30 | 6 | 49 |
| Withdrew: Refused continuation of study medication | 0 | 2 | 0 | 1 |
| Withdrew: Other than stated | 2 | 1 | 0 | 3 |
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.
| percentage of participants | Afatinib |
|---|---|
| Objective Response (OR) as Determined by RECIST 1.0 | 62.0 (53.1 to 70.4) |
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.
| Percentage of participants | Afatinib |
|---|---|
| Clinical Benefit as Determined by RECIST 1.0 | 82.2 (74.5 to 88.3) |
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.
| weeks | Afatinib |
|---|---|
| Duration of Clinical Benefit | 81.6 ± 80.5 |
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.
| Weeks | Afatinib |
|---|---|
| Duration of Objective Response | 76.5 ± 77.2 |
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.
| Percentage of participants | Afatinib |
|---|---|
| Week 4 | 38.8 |
| Week 8 | 12.4 |
| Week 12 | 1.6 |
| Week 20 | 5.4 |
| Week 28 | 0.0 |
| Week 36 | 1.6 |
| Week 44 | 0.0 |
| >= Week 52 | 2.3 |
| no objective response | 38.0 |
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.
| Months | Afatinib |
|---|---|
| Progression-free Survival | 10.2 (8.1 to 13.7) |
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.
| Months | Afatinib |
|---|---|
| Overall Survival Time | 26.8 (22.0 to 34.5) |
Predose concentration of the analyte in plasma at steady state immediately before administration of the 29th dose (Cpre,ss,29).
| ng/mL | Afatinib 30 mg | Afatinib 40 mg | Afatinib 50 mg |
|---|---|---|---|
| Cpre,ss,29 | 54.1 ± 78.5 | 27.9 ± 63.1 | 33.7 ± 64.1 |
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).
| Percentage of participants | BIBW 40mg | BIBW 50mg |
|---|---|---|
| skin reactions | 16.7 | 27.3 |
| gastrointestinal (GI) | 100.0 | 97.0 |
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).
| Percentage of participants | BIBW 40mg | BIBW 50mg |
|---|---|---|
| Grade 1 | 3.3 | 1.0 |
| Grade 2 | 36.7 | 25.3 |
| Grade 3 | 46.7 | 57.6 |
| Grade 4 | 6.7 | 3.0 |
| Grade 5 | 6.7 | 12.1 |
Collected over First administration of trial medication until 28 days after last administration of trial medication, up to 93 months.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| BIBW 40mg | — | 9/30 (30%) | 30/30 (100%) |
| BIBW 50mg | — | 44/99 (44.4%) | 98/99 (99%) |
| Event | BIBW 40mg | BIBW 50mg |
|---|---|---|
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/30 | 7/99 |
| Neoplasm progressionNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 2/30 | 1/99 |
| PneumothoraxRespiratory, thoracic and mediastinal disorders | 2/30 | 0/99 |
| PneumoniaInfections and infestations | 0/30 | 4/99 |
| Intracranial pressure increasedNervous system disorders | 0/30 | 4/99 |
| NauseaGastrointestinal disorders | 1/30 | 2/99 |
| VomitingGastrointestinal disorders | 1/30 | 1/99 |
| Chest painGeneral disorders | 1/30 | 0/99 |
| FatigueGeneral disorders | 1/30 | 0/99 |
| PyrexiaGeneral disorders | 1/30 | 2/99 |
| Event | BIBW 40mg | BIBW 50mg |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 29/30 | 92/99 |
| ParonychiaInfections and infestations | 20/30 | 79/99 |
| RashSkin and subcutaneous tissue disorders | 20/30 | 75/99 |
| PruritusSkin and subcutaneous tissue disorders | 15/30 | 60/99 |
| RhinorrhoeaRespiratory, thoracic and mediastinal disorders | 11/30 | 46/99 |
| CoughRespiratory, thoracic and mediastinal disorders | 9/30 | 41/99 |
| Mucosal inflammationGeneral disorders | 8/30 | 39/99 |
| Decreased appetiteMetabolism and nutrition disorders | 10/30 | 39/99 |
| StomatitisGastrointestinal disorders | 3/30 | 37/99 |
| FolliculitisInfections and infestations | 7/30 | 36/99 |
Treated set: The patients who had taken at least one dose of afatinib were included in the treated set.
| Age, Continuous(years) | First-line Afatinib 40 mg | First-line Afatinib 50 mg | Second-line Afatinib 40 mg | Second-line Afatinib 50 mg | Total |
|---|---|---|---|---|---|
| Mean | 64 ± 11.0 | 62 ± 9.6 | 57 ± 14.5 | 61 ± 11.5 | 62 ± 11.1 |
| Sex: Female, Male(Participants) | First-line Afatinib 40 mg | First-line Afatinib 50 mg | Second-line Afatinib 40 mg | Second-line Afatinib 50 mg | Total |
|---|---|---|---|---|---|
| Female | 13 | 27 | 3 | 32 | 75 |
| Male | 10 | 11 | 4 | 29 | 54 |
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Carcinoma, Non-Small-Cell Lung→
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