Clinical Trial Results:
A 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
|
Summary
|
|
EudraCT number |
2010-023869-21 |
Trial protocol |
FI |
Global end of trial date |
20 Nov 2013
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
14 Jul 2016
|
First version publication date |
06 Aug 2015
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
ML25575
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01287754 | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
F. Hoffmann-La Roche AG
|
||
Sponsor organisation address |
Grenzacherstrasse 124, Basel, Switzerland, CH-4070
|
||
Public contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
|
||
Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
03 Nov 2014
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
20 Nov 2013
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
20 Nov 2013
|
||
Was the trial ended prematurely? |
Yes
|
||
|
General information about the trial
|
|||
Main objective of the trial |
The study was designed to assess the efficacy of erlotinib (Tarceva[TM]; 150 milligrams [mg]) on progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) in locally advanced or metastatic stages (stage IIIB and stage IV) who have not received previous chemotherapy for their disease and who present activating mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (EGFR).
|
||
Protection of trial subjects |
This study was done in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
22 Mar 2011
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Finland: 24
|
||
Worldwide total number of subjects |
24
|
||
EEA total number of subjects |
24
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
11
|
||
From 65 to 84 years |
12
|
||
85 years and over |
1
|
||
|
|||||||||||||||||||||||||||||
|
Recruitment
|
|||||||||||||||||||||||||||||
Recruitment details |
- | ||||||||||||||||||||||||||||
|
Pre-assignment
|
|||||||||||||||||||||||||||||
Screening details |
All participants underwent EGFR mutation testing at Screening. Those positive for the EGFR mutation and who met eligibility criteria (number of participants [n] = 3) received treatment with erlotinib. The remaining participants (n = 21) were followed for overall survival but did not receive treatment. | ||||||||||||||||||||||||||||
|
Period 1
|
|||||||||||||||||||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||||||||||||||||||
Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
|
||||||||||||||||||||||||||||
Blinding used |
Not blinded | ||||||||||||||||||||||||||||
|
Arms
|
|||||||||||||||||||||||||||||
Are arms mutually exclusive |
No
|
||||||||||||||||||||||||||||
|
Arm title
|
Erlotinib | ||||||||||||||||||||||||||||
Arm description |
Participants positive for the EGFR mutation and who met eligibility criteria received treatment with erlotinib, 150 mg orally once daily until disease progression or unacceptable toxicity. | ||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Erlotinib
|
||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||
Dosage and administration details |
Participants received treatment with erlotinib, 150 mg orally once daily until disease progression or unacceptable toxicity.
|
||||||||||||||||||||||||||||
|
Arm title
|
Untreated | ||||||||||||||||||||||||||||
Arm description |
Participants without the EGFR mutation were followed for overall survival but did not receive treatment. Additionally, participants positive for the EGFR mutation who were excluded from treatment were followed for overall survival. | ||||||||||||||||||||||||||||
Arm type |
No intervention | ||||||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
|
||||||||||||||||||||||||||||
|
Arm title
|
Total Population | ||||||||||||||||||||||||||||
Arm description |
All participants underwent EGFR mutation testing at Screening. Those positive for the EGFR mutation and who met eligibility criteria (n = 3) received treatment with erlotinib, 150 mg orally once daily until disease progression or unacceptable toxicity. The remaining participants (n = 21) were followed for overall survival but did not receive treatment. | ||||||||||||||||||||||||||||
Arm type |
Experimental or no intervention | ||||||||||||||||||||||||||||
Investigational medicinal product name |
Erlotinib
|
||||||||||||||||||||||||||||
Investigational medicinal product code |
|||||||||||||||||||||||||||||
Other name |
|||||||||||||||||||||||||||||
Pharmaceutical forms |
Tablet
|
||||||||||||||||||||||||||||
Routes of administration |
Oral use
|
||||||||||||||||||||||||||||
Dosage and administration details |
Eligible participants (n = 3) received treatment with erlotinib, 150 mg orally once daily until disease progression or unacceptable toxicity.
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Erlotinib
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants positive for the EGFR mutation and who met eligibility criteria received treatment with erlotinib, 150 mg orally once daily until disease progression or unacceptable toxicity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Untreated
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants without the EGFR mutation were followed for overall survival but did not receive treatment. Additionally, participants positive for the EGFR mutation who were excluded from treatment were followed for overall survival. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Total Population
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All participants underwent EGFR mutation testing at Screening. Those positive for the EGFR mutation and who met eligibility criteria (n = 3) received treatment with erlotinib, 150 mg orally once daily until disease progression or unacceptable toxicity. The remaining participants (n = 21) were followed for overall survival but did not receive treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Erlotinib
|
||
Reporting group description |
Participants positive for the EGFR mutation and who met eligibility criteria received treatment with erlotinib, 150 mg orally once daily until disease progression or unacceptable toxicity. | ||
Reporting group title |
Untreated
|
||
Reporting group description |
Participants without the EGFR mutation were followed for overall survival but did not receive treatment. Additionally, participants positive for the EGFR mutation who were excluded from treatment were followed for overall survival. | ||
Reporting group title |
Total Population
|
||
Reporting group description |
All participants underwent EGFR mutation testing at Screening. Those positive for the EGFR mutation and who met eligibility criteria (n = 3) received treatment with erlotinib, 150 mg orally once daily until disease progression or unacceptable toxicity. The remaining participants (n = 21) were followed for overall survival but did not receive treatment. | ||
|
|||||||||
End point title |
Progression-Free Survival (PFS) among Erlotinib-Treated Participants with the EGFR Mutation [1] [2] | ||||||||
End point description |
PFS was defined as the time from the first dose of erlotinib to the first documentation of disease progression or death, whichever occurred first. Tumor progression was determined using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), which defines progression as a 20 percent (%) or greater increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeters (mm), or the appearance of one or more new lesions. PFS was calculated in months as [first event date minus first dose date plus 1] divided by 30.44. All participants who received at least one dose of erlotinib were included in the analysis. (99999 = not estimable because data for 1 of 3 participants were censored, and thus a confidence interval upper limit was not reached.)
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Per standard of care (every 3 months) until discontinuation for up to approximately 2 years
|
||||||||
| 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: Statistical analysis was not performed and/or reported because there were no statistical assumptions. Only descriptive statistics were planned. [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Erlotinib-treated participants were analyzed for all reported outcome measures; untreated participants were only followed for overall survival and are thus only included in the survival outcome measures. Except for the percentage of participants with EGFR mutation at Screening, outcome measures were not analyzed for the total collective population. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||
End point title |
Number of Erlotinib-Treated Participants with the EGFR Mutation with an Objective Response per RECIST v1.1 [3] | ||||||||||
End point description |
Objective tumor response was assessed by the investigator using RECIST v1.1 and recorded as complete response (CR), partial response (PR), or unmeasurable. RECIST v1.1 defines CR as disappearance of all target lesions, with short-axis reduction to less than (<) 10 mm for any pathological lymph nodes, and PR as a 30% or greater reduction from baseline in the sum of diameters of target lesions. All participants who received at least one dose of erlotinib were included in the analysis.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Per standard of care (every 3 months) until discontinuation for up to approximately 2 years
|
||||||||||
| Notes [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Erlotinib-treated participants were analyzed for all reported outcome measures; untreated participants were only followed for overall survival and are thus only included in the survival outcome measures. Except for the percentage of participants with EGFR mutation at Screening, outcome measures were not analyzed for the total collective population. |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||
End point title |
Overall Survival (OS) among Erlotinib-Treated and Untreated Participants [4] | ||||||||||||
End point description |
OS was defined as the time from recorded diagnosis to death from any cause or last patient last visit. OS was calculated in months as [death date or last-known alive date minus diagnosis date plus 1] divided by 30.44. All erlotinib-treated participants who received at least one dose of erlotinib, in addition to all enrolled untreated participants, were included in the analysis. (99999 = not estimable because data for 1 of 3 participants were censored, and thus a confidence interval upper limit was not reached.)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Per standard of care (every 3 months) until discontinuation for up to approximately 2 years
|
||||||||||||
| Notes [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Erlotinib-treated participants were analyzed for all reported outcome measures; untreated participants were only followed for overall survival and are thus only included in the survival outcome measures. Except for the percentage of participants with EGFR mutation at Screening, outcome measures were not analyzed for the total collective population. |
|||||||||||||
|
|||||||||||||
| No statistical analyses for this end point | |||||||||||||
|
||||||||||||||||
End point title |
Percentage of Participants Alive at 6 and 12 Months [5] | |||||||||||||||
End point description |
Death from any cause was documented at 6 and 12 months from recorded diagnosis. The percentage of participants alive at each timepoint was calculated as [number of participants alive divided by number enrolled] multiplied by 100. All erlotinib-treated participants who received at least one dose of erlotinib, in addition to all enrolled untreated participants, were included in the analysis.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
At 6 and 12 months
|
|||||||||||||||
| Notes [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Erlotinib-treated participants were analyzed for all reported outcome measures; untreated participants were only followed for overall survival and are thus only included in the survival outcome measures. Except for the percentage of participants with EGFR mutation at Screening, outcome measures were not analyzed for the total collective population. |
||||||||||||||||
|
||||||||||||||||
| No statistical analyses for this end point | ||||||||||||||||
|
|||||||
End point title |
Percentage of Participants with EGFR Mutation at Screening [6] | ||||||
End point description |
Participants were tested at Screening for the presence of activating mutations in the tyrosine kinase domain of EGFR. The percentage of participants with mutation was calculated as [number of mutation-positive participants divided by number tested] multiplied by 100. All erlotinib-treated participants who received at least one dose of erlotinib, in addition to all enrolled untreated patients, were included in the analysis.
|
||||||
End point type |
Secondary
|
||||||
End point timeframe |
Screening
|
||||||
| Notes [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Erlotinib-treated participants were analyzed for all reported outcome measures; untreated participants were only followed for overall survival and are thus only included in the survival outcome measures. The percentage of participants with EGFR mutation at Screening was reported for the total collective population. |
|||||||
|
|||||||
| No statistical analyses for this end point | |||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 2 years
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Only participants treated with erlotinib were assessed for adverse events.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
NCI CTC-AE | ||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Erlotinib
|
||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants positive for the EGFR mutation and who met eligibility criteria received treatment with erlotinib, 150 mg orally once daily until disease progression or unacceptable toxicity. | ||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
13 Sep 2011 |
The study design was modified to collect follow-up information on survival in each study arm. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
