Clinical Trial Results:
An open-label, single-arm phase IV study to assess the efficacy and safety of afatinib as second-line therapy for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring an Epidermal growth factor receptor (EGFR) mutation (Del19 or L858R) who have failed first-line treatment with platinum-based chemotherapy
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Summary
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EudraCT number |
2014-001077-14 |
Trial protocol |
RO PL |
Global end of trial date |
13 Jun 2017
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Results information
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Results version number |
v1 |
This version publication date |
21 Jun 2018
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First version publication date |
21 Jun 2018
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Other versions |
v2 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
1200.217
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02208843 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Boehringer Ingelheim
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Sponsor organisation address |
Binger Strasse 173, Ingelheim am Rhein, Germany, 55216
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Public contact |
QRPE Processes and Systems Coordination Clinical Trial Information Disclosure, Boehringer Ingelheim, 001 8002430127, clintriage.rdg@boehringer-ingelheim.com
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Scientific contact |
QRPE Processes and Systems Coordination Clinical Trial Information Disclosure, Boehringer Ingelheim, 001 8002430127, clintriage.rdg@boehringer-ingelheim.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
03 Jul 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 May 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Jun 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The objective of this single-arm, open-label trial was to assess the efficacy and safety of afatinib as second-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harbouring an epidermal growth factor receptor (EGFR) mutation (Del19 and/or L858R) who had failed first-line platinumbased chemotherapy.
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Protection of trial subjects |
Only subjects that met all the study inclusion and none of the exclusion criteria were to be entered in the study. All subjects were free to withdraw from the clinical trial at any time for any reason given. Close monitoring of all subjects was adhered to throughout the trial conduct. Rescue medication was allowed for all patients as required.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Nov 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Egypt: 17
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Country: Number of subjects enrolled |
Philippines: 6
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Country: Number of subjects enrolled |
Poland: 7
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Country: Number of subjects enrolled |
Romania: 15
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Country: Number of subjects enrolled |
Serbia: 6
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Country: Number of subjects enrolled |
Thailand: 19
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Worldwide total number of subjects |
70
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EEA total number of subjects |
22
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
46
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From 65 to 84 years |
24
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85 years and over |
0
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Recruitment
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Recruitment details |
An open-label, single-arm phase IV, a total of 70 patients were enrolled by multinational trial at 24 sites in 7 countries. Of the 70 enrolled patients, 60 patients were entered the trial and 60 were treated. | ||||||||||||||||||||||
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Pre-assignment
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Screening details |
All patients were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that all subjects met all inclusion/exclusion criteria. Subjects were not to be entered to trial treatment if any one of the specific entry criteria were not met. | ||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||||
Blinding implementation details |
This is Non-Randomised and Non controlled trial
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Arms
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Arm title
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Afatinib 40 mg | ||||||||||||||||||||||
Arm description |
All patients received continuous daily treatment with Afatinib at a starting dose of 40 miligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food. | ||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||
Investigational medicinal product name |
Afatinib
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Film-coated tablet
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Routes of administration |
Oral use
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Dosage and administration details |
All patients were orally received continuous daily treatment with Afatinib at a starting dose of 40 miligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs).
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Baseline characteristics are based on patients who were randomized after successfully completing the screening period and received at least one dose of the trial medication. |
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Baseline characteristics reporting groups
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Reporting group title |
Afatinib 40 mg
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Reporting group description |
All patients received continuous daily treatment with Afatinib at a starting dose of 40 miligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Afatinib 40 mg
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Reporting group description |
All patients received continuous daily treatment with Afatinib at a starting dose of 40 miligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food. | ||
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End point title |
Objective tumour response (complete response [CR], partial response [PR]) as assessed by the investigator according to the RECIST version 1.1 [1] | ||||||||
End point description |
As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by Magnetic resonance imaging (MRI): Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions
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End point type |
Primary
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End point timeframe |
Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: This endpoint was evaluated only descriptively. Thus, no statistical hypothesis were tested. |
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| Notes [2] - TS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free survival (PFS) as assessed by the investigator according to RECIST 1.1. | ||||||||
End point description |
Progression-free survival (PFS) is the time from treatment start to disease progression (or death if the patient died before progression). PFS as assessed based on investigator review according to the response evaluation criteria in solid tumours (RECIST) version 1.1.
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End point type |
Secondary
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End point timeframe |
Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days
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| Notes [3] - TS |
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| No statistical analyses for this end point | |||||||||
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End point title |
Disease control (CR, PR, stable disease [SD]) as assessed by the investigator according to RECIST 1.1 | ||||||||
End point description |
As Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), disappearance of all target lesions; Partial Response (PR), =30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
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End point type |
Secondary
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End point timeframe |
Post baseline tumour-imaging was performed at every 8 weeks until Week 56 and then every 12 weeks; up to 802 days
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| Notes [4] - TS |
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From first drug administration until 28 days after last drug administration, up to 830 days.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Afatinib 40 mg
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Reporting group description |
All patients received continuous daily treatment with Afatinib at a starting dose of 40 miligram (mg), treatment interruption and reduction scheme to 30 mg and then to 20 mg were permitted to manage treatment-related adverse events (AEs). Patients were orally administered with the film coated tablet once a day without food. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
