Clinical Trial Results:
An Open-Label, Multicentre, Single-Arm Study to Characterise the Efficacy, Safety, and Tolerability of Gefitinib 250 mg (IRESSA™1) as First-Line Treatment in Caucasian Patients Who Have Epidermal Growth Factor Receptor (EGFR) Mutation-Positive Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)
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Summary
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EudraCT number |
2010-018614-70 |
Trial protocol |
PT ES GB FR IT NO HU GR BG |
Global end of trial date |
06 Jun 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Jun 2017
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First version publication date |
10 Jun 2017
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Other versions |
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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 |
D791AC00014
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
AstraZeneca
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Sponsor organisation address |
One Medimmune Way, 101 ORD, 2233C, Gaithersburg, United States, MD 20878
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Public contact |
Yuri Rukazenkov, AstraZeneca, +44 01625 231825, yuri.rukazenkov@astrazeneca.com
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Scientific contact |
Yuri Rukazenkov, AstraZeneca, +44 01625 231825, yuri.rukazenkov@astrazeneca.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 |
15 Aug 2012
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Aug 2012
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Global end of trial reached? |
Yes
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Global end of trial date |
06 Jun 2016
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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 primary objective of this study was to evaluate the ORR (confirmed complete response [CR] or partial response [PR]) of gefitinib using Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1, in Caucasian patients with Activating sensitising EGFR mutation-positive (EGFR M+) Non-small cell lung cancer (NSCLC).
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
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Background therapy |
- | ||
Evidence for comparator |
This was a single arm trial - there were no comparators | ||
Actual start date of recruitment |
08 Sep 2010
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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 |
Bulgaria: 2
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Country: Number of subjects enrolled |
France: 2
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Country: Number of subjects enrolled |
Greece: 8
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Country: Number of subjects enrolled |
Hungary: 20
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Country: Number of subjects enrolled |
Italy: 5
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Country: Number of subjects enrolled |
Norway: 2
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Country: Number of subjects enrolled |
Portugal: 7
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Country: Number of subjects enrolled |
Romania: 19
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Country: Number of subjects enrolled |
Spain: 15
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Country: Number of subjects enrolled |
Switzerland: 1
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Country: Number of subjects enrolled |
Turkey: 7
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Country: Number of subjects enrolled |
United Kingdom: 7
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Country: Number of subjects enrolled |
Poland: 12
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Worldwide total number of subjects |
107
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EEA total number of subjects |
99
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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) |
53
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From 65 to 84 years |
54
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85 years and over |
0
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Recruitment
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Recruitment details |
1060 Caucasian patients with locally advanced or metastatic NSCLC were screened, and 118 patients had activating sensitizing EGFR mutation eligible for the study (EGFR M+). 107 patients received at least 1 dose of gefitinib: 106 were EGFR M+ and one EGFR M+I (ineligible). | ||||||||||||||||||
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Pre-assignment
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Screening details |
1060 Caucasian patients with locally advanced or metastatic NSCLC were screened, and 118 patients had activating sensitizing EGFR mutation eligible for the study (EGFR M+). 107 patients received at least 1 dose of gefitinib: 106 were EGFR M+ and one EGFR M+I (ineligible). | ||||||||||||||||||
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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 | ||||||||||||||||||
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Arms
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Arm title
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Gefitinib | ||||||||||||||||||
Arm description |
Gefitinib 250 mg oral tablets once daily, administered continuously from Visit 2 until objective disease progression was documented or any other criterion for discontinuation was met. Gefitinib tablets were taken at approximately the same time each day. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Iressa
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
250mg tablet once daily
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Baseline characteristics reporting groups
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Reporting group title |
Gefitinib
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Reporting group description |
Gefitinib 250 mg oral tablets once daily, administered continuously from Visit 2 until objective disease progression was documented or any other criterion for discontinuation was met. Gefitinib tablets were taken at approximately the same time each day. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Gefitinib
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Reporting group description |
Gefitinib 250 mg oral tablets once daily, administered continuously from Visit 2 until objective disease progression was documented or any other criterion for discontinuation was met. Gefitinib tablets were taken at approximately the same time each day. | ||
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End point title |
Objective response rate (ORR) (Investigator) [1] | ||||||||||
End point description |
% of patients in the Full analysis set who have a complete response [CR] or partial response [PR] confirmed by repeat imaging at least 4 weeks later with no evidence of progression between confirmation visits (as defined by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1)). CR: disappearance of all target lesions (TLs) & non-target lesions (NTLs). PR: >= 30% decrease in the sum of diameters compared to baseline (with no evidence of progression) and the NTLs are at least stable with no evidence of new lesions. Outcome is based on measurements made at site by investigator.
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End point type |
Primary
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End point timeframe |
Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months
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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 is a single arm study with no planned comparative analysis and so non is included in this form |
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| Notes [2] - One subject excluded from analysis as not eligible for study |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Disease Control Rate (DCR) (Investigator) | ||||||||||
End point description |
DCR is calculated as the % of the FAS patient population with a best visit response of CR, PR (a visit response of CR or PR which is confirmed at least 4 weeks later) or stable disease (SD). SD is defined as no evidence of CR, PR or progression and must have occurred at a minimum of 6 weeks after first dose of study treatment. (progression is defined as ≥20% increase in the sum of the diameters of target lesions from minimum; clinically significant progression in non-target lesions; the presence of a new lesion or death). Outcome is based on measurements made at site by investigator.
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End point type |
Secondary
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End point timeframe |
Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months
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| Notes [3] - One subject excluded from analysis as not eligible for study. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Progression - Free Survival (PFS) (Investigator) | ||||||||
End point description |
PFS was defined as the time from the first dose of gefitinib study treatment until objective disease progression as defined by RECIST 1.1 (≥20% increase in the sum of the diameters of target lesions from minimum, clinically significant progression in non-target lesions or the presence of a new lesion) or death (by any cause in the absence of progression). Progression is based on measurements made at site by investigator.
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End point type |
Secondary
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End point timeframe |
Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months
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| Notes [4] - One subject excluded from analysis as not eligible for study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival (OS) | ||||||||
End point description |
OS was defined as the time from first dose of gefitinib study treatment until death by any cause. Patients who had not died at the time of analysis were censored at the last date the patient was known to be alive.
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End point type |
Secondary
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End point timeframe |
Survival follow up from first dose of gefitinib till death of the patient or till end of study in absence of death.
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| Notes [5] - NB Upper limit of confidence interval for Median is Not Calculable due to insufficient data. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Disease Control Rate (DCR) (Independent central review) | ||||||||||
End point description |
DCR is calculated as the % of the FAS patient population with a best visit response of CR, PR (a visit response of CR or PR which is confirmed at least 4 weeks later) or stable disease (SD). SD is defined as no evidence of CR, PR or progression and must have occurred at a minimum of 6 weeks after first dose of study treatment. (progression is defined as ≥20% increase in the sum of the diameters of target lesions from minimum; clinically significant progression in non-target lesions; the presence of a new lesion or death). Outcome is based on measurements of scans by central review.
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End point type |
Other pre-specified
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End point timeframe |
Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months
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| Notes [6] - One subject excluded from analysis as not eligible for study. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Objective response rate (ORR) (Independent central review)) | ||||||||||
End point description |
% of patients in the Full analysis set who have a complete response [CR] or partial response [PR] confirmed by repeat imaging at least 4 weeks later with no evidence of progression between confirmation visits (as defined by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1)). CR: disappearance of all target lesions (TLs) & non-target lesions (NTLs). PR: >= 30% decrease in the sum of diameters compared to baseline (with no evidence of progression) and the NTLs are at least stable with no evidence of new lesions. Outcome is based on measurements of scans by central review.
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End point type |
Other pre-specified
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End point timeframe |
Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months
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| Notes [7] - One subject excluded from analysis as not eligible for study. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Progression - Free Survival (PFS) (Independent central review) | ||||||||
End point description |
PFS was defined as the time from the first dose of gefitinib study treatment until objective disease progression as defined by RECIST 1.1 (≥20% increase in the sum of the diameters of target lesions from minimum, clinically significant progression in non-target lesions or the presence of a new lesion) or death (by any cause in the absence of progression). Progression is based on measurements of scans by central review.
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End point type |
Other pre-specified
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End point timeframe |
Scans taken at baseline and then follow up assessments taken every 6 weeks until progression, or last evaluable assessment in the absence of progression, assessed up to 23 months
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| Notes [8] - One subject excluded from analysis as not eligible for study. |
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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 |
Adverse Events and Serious Adverse Events were collected from the time of screening informed consent throughout the treatment period, until 30 days after discontinuation of gefitinib treatment. All ongoing AEs & SAEs were to be followed until resolution.
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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 |
15
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Reporting groups
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Reporting group title |
Gefitinib 250 mg
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Reporting group description |
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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? Yes | |||
Date |
Amendment |
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27 Jan 2011 |
The amendment included the following updates to the protocol:
- Final IPASS OS analysis had been conducted and new data were added to the CSP.
-New safety information regarding gastrointestinal perforation reported in patients taking IRESSA, in most cases this was associated with other known risk factors, including increasing age, concomitant medications such as steroids or NSAIDS, underlying history of GI ulceration, smoking or bowel metastases at sites of perforation.
-Clarification of exclusion criteria no 3, that patients considered to require radiotherapy to the lung at the time of study entry or in the near future are excluded from the study.
-Clarification that residual material (tumour) may be used for optional exploratory biomarker research if consent has been obtained for this research.
-Clarification that Residual material (tumour, plasma, serum) will be stored for a maximum of 25 years.
-Clarification that for each of the following objectives: ORR, DCR, PFS and OS, the mutation sub type of the positive mutations will be considered as subgroups. |
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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 | |||
