Clinical Trial Results:
Phase II, Open-Label Study of Erlotinib (Tarceva®) Treatment in Patients with Locally Advanced or Metastatic Non-Small-Cell Lung Cancer Who Present Activating Mutations in the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor (EGFR) - (TRIGGER)
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Summary
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EudraCT number |
2010-023892-24 |
Trial protocol |
IT |
Global end of trial date |
31 Jan 2017
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Results information
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Results version number |
v2(current) |
This version publication date |
06 Jan 2018
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First version publication date |
31 Jul 2016
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Other versions |
v1 |
Version creation reason |
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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 |
ML25514
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01378962 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Study Name: TRIGGER | ||
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Sponsors
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Sponsor organisation name |
F. Hoffmann-La Roche AG
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Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
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Public contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
F. Hoffmann-La Roche AG, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.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 |
31 Jan 2017
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jan 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 |
This single-arm, open-label study evaluated the efficacy and safety of Tarceva (erlotinib) in subjects with locally advanced or metastatic non-small cell lung cancer. Subjects received a daily oral doses of 150 mg Tarceva. The anticipated time on study treatment was 12 months.
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Protection of trial subjects |
All study subjects were required to read and sign an Informed Consent Form.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
31 Mar 2011
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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 |
Italy: 50
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Worldwide total number of subjects |
50
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EEA total number of subjects |
50
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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) |
26
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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 |
- | ||||||||||||||
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Pre-assignment
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Screening details |
Fifty-one subjects were screened among the 7 centers involved in this study, however one patient was considered a screening failure and was not included in the enrolled population. | ||||||||||||||
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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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Erlotinib 150 mg | ||||||||||||||
Arm description |
Erlotinib 150 milligrams (mg) tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal. | ||||||||||||||
Arm type |
Experimental | ||||||||||||||
Investigational medicinal product name |
Erlotinib
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Investigational medicinal product code |
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Other name |
Tarceva
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal.
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Baseline characteristics reporting groups
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Reporting group title |
Erlotinib 150 mg
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Reporting group description |
Erlotinib 150 milligrams (mg) tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Erlotinib 150 mg
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Reporting group description |
Erlotinib 150 milligrams (mg) tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal. | ||
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End point title |
Percentage of Subjects with Disease Progression or Death at 12 Months After Baseline [1] | ||||||||
End point description |
According to Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST v1.1), progressive disease (PD) was defined as at least a 20 percent (%) increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Intent to treat (ITT) population included all subjects enrolled in the study who received at least one dose of treatment.
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End point type |
Primary
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End point timeframe |
12 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: No statistical analyses were performed as this study has only one arm. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-Free Survival (PFS) [2] | ||||||||
End point description |
PFS was defined as the time from baseline to the date of first occurrence of disease progression or death. According to RECIST v1.1, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. PFS was assessed using Kaplan-Meier method. ITT population included all subjects enrolled in the study who received at least one dose of treatment.
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End point type |
Primary
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End point timeframe |
Up to 1 year after enrollment of the last participant (maximum up to 27 months)
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| Notes [2] - 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: No statistical analyses were performed as this study has only one arm. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Probability of Being Progression Free 12 Months after Baseline [3] | ||||||||
End point description |
According to RECIST v1.1, PD was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. ITT population included all subjects enrolled in the study who received at least one dose of treatment.
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End point type |
Primary
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End point timeframe |
12 months
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| Notes [3] - 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: No statistical analyses were performed as this study has only one arm. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects who Died | ||||||||
End point description |
ITT population included all subjects enrolled in the study who received at least one dose of treatment.
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End point type |
Secondary
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End point timeframe |
Every 8 weeks during treatment, after discontinuation participants were followed for up to 1 year after enrollment of the last participant (maximum up to 27 months)
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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 randomization to the date of death due to any cause. OS was assessed using Kaplan-Meier method. ITT population included all subjects enrolled in the study who received at least one dose of treatment.
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End point type |
Secondary
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End point timeframe |
Every 8 weeks during treatment, after discontinuation participants were followed for up to 1 year after enrollment of the last participant (maximum up to 27 months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects With a Response by Best Overall Response | ||||||||||||||||||
End point description |
Tumour response assessed to RECIST v1.1. Complete response(CR): complete disappearance of all target lesions & non-target disease, with exception of nodal disease. All nodes must decrease to normal (short axis<10 mm), and no new lesions. Partial response(PR): greater than or equal to (>=) 30% decrease under baseline of sum of diameters of all target lesions. The short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. No unequivocal progression of non-target disease, and no new lesions. PD: >=20% increase in sum of longest diameter of target lesions, taking as reference smallest sum of longest diameter recorded since treatment started or appearance of 1 or more new lesions. For non-target lesions, appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions. Stable disease(SD): not qualifying for CR, PR, or PD. ITT population: all subjects enrolled who took at least one dose of treatment.
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End point type |
Secondary
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End point timeframe |
Baseline up to disease progression or end of study (up to 12 Months)
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Percentage of Subjects With Objective Response | ||||||||
End point description |
Objective response: percentage of subjects with CR or PR as best overall response by RECIST v1.1. Status of PR or CR was assigned if changes in tumour measurements were confirmed by repeated assessments no less than 4 weeks after criteria for response were first met. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than 10 mm), with no new lesions. PR was defined as >=30% decrease under baseline of sum of diameters of all target lesions. Short axis was used in sum for target nodes, while longest diameter was used in sum for all other target lesions. No unequivocal progression of non-target disease, and no new lesions. Non-responders: subjects with no tumour assessment after start of treatment. Percentage of subjects with response is presented. ITT population: all subjects enrolled who received at least one dose of treatment.
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End point type |
Secondary
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End point timeframe |
Baseline up to disease progression or end of study (up to 12 Months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects Achieving CR, PR, or SD as Best Overall Response | ||||||||
End point description |
The Disease Control Rate was defined as the percentage of subjects who had CR or PR or SD as Best Overall Response achieved within the time between the first drug administration and documented disease progression or end of study. According to RECIST v1.1, CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis less than 10 mm), with no new lesions. PR was defined as >=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease, and no new lesions. SD was defined as not qualifying for CR, PR, or PD. ITT population included all subjects enrolled in the study who received at least one dose of treatment.
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End point type |
Secondary
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End point timeframe |
Baseline up to disease progression or end of study (up to 12 Months)
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Subjects with Primary and Secondary Resistance | ||||||||||||
End point description |
Primary resistance: subjects did not reach SD or PR or CR before going to PD. Secondary resistance: subjects had PD after reached SD or PR or CR at least once. CR: complete disappearance of all target lesions and non-target disease, with exception of nodal disease. All nodes must decrease to normal (short axis < 10 mm), with no new lesions. PR: >=30% decrease under baseline of sum of diameters of all target lesions. Short axis was used in sum for target nodes, and longest diameter was used in sum for all other target lesions. No unequivocal progression of non-target disease, and no new lesions. PD: >=20% increase in sum of longest diameter of target lesions, taking as reference smallest sum of longest diameter recorded since treatment started or appearance of 1 or more (>=1) new lesions. For non-target lesions, appearance of >=1 new lesions and/or unequivocal progression of existing non-target lesions. ITT population: all subjects enrolled who received at least one dose of treatment.
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End point type |
Secondary
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End point timeframe |
Baseline up to disease progression (up to 12 Months)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Subjects With Epidermal Growth Factor Receptor (EGFR) Mutation by Mutation Type | ||||||||||||||||||||||||
End point description |
EGFR is a gene in the tumour tissues and mutations in this gene have been linked to a variety of tumors. Presence or absence of EGFR mutation was determined in liquid biopsies by reverse transcriptase-polymerase chain reaction (RT-PCR /Cobas).
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End point type |
Secondary
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End point timeframe |
Baseline, At progression of disease (up to 12 Months)
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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 |
Up to 1 year after enrollment of the last participant (maximum up to 27 months)
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Adverse event reporting additional description |
Safety population included all subjects enrolled in the study who received at least one dose of treatment and had at least one safety assessment.
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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 |
14.0
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Reporting groups
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Reporting group title |
Erlotinib 150 mg
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Reporting group description |
Erlotinib 150 mg tablet orally once daily up to end of study (12 months) or until disease progression, unacceptable toxicity or consent withdrawal. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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28 Jan 2013 |
Amendment 1 introduced a descriptive, interim analysis of clinical characteristics at baseline including the EGFR mutation test results obtained from basal tumor biopsies, from circulating tumor cells and plasma DNA and by immunohistochemical detection. Moreover, a descriptive analysis was performed on data collected up to January 2013 concerning data on demographics, disease history, treatment dose and duration, the incidence of rash, EGFR mutation test, results from both local and central laboratory, at baseline and at progression, stratifying patients according to their undergoing disease progression or not at the date of the analysis. No change in the experimental design was foreseen based on the analysis results. Since no model analyses on primary or secondary end-points were performed, no correction of the overall alpha level was applied. |
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08 Jul 2013 |
Amendment 2 ensured that patients who did not have progressive disease at the end of the study were able to continue to receive the study drug. For these patients, the protocol called for a reduction of dosage to 50 mg. Since the 25 mg dose is not commercialized in Italy, Roche provided the study drug until progression, unacceptable toxicity or consent withdrawal. No further data was to be captured for these patients. Nevertheless, adverse events (SAEs) continued to be collected and were reported as outlined in the study protocol. |
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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 | |||
