Clinical Trial Results:
Biomarkers Impact on the Response to Treatment With Erlotinib in First Line Non-small Cell Lung Cancer With EGFR Activating Mutations - BIOTEC
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Summary
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EudraCT number |
2009-017063-42 |
Trial protocol |
RO |
Global end of trial date |
14 Jul 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
24 Mar 2017
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First version publication date |
24 Mar 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 |
ML22606
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01153984 | ||
WHO universal trial number (UTN) |
- | ||
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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 |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 616878333, global.trial_information@roche.com
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Scientific contact |
Roche Trial Information Hotline, 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 |
14 Jul 2015
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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 |
14 Jul 2015
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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 is a multi-center open-label, single arm, Phase II trial with erlotinib as first-line therapy in participants who are chemotherapy-naive with advanced and/or metastatic (Stage IIIB/ IV) non-small cell lung cancer (NSCLC) and endothelial growth factor receptor (EGFR) activating mutations to assess the progression free survival, time to progression, objective response rate, and 1-year survival rate.
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Protection of trial subjects |
The study was conducted in accordance with the principles of the “Declaration of Helsinki” and Good Clinical Practice (GCP).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
01 Jun 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 |
Romania: 23
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Worldwide total number of subjects |
23
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EEA total number of subjects |
23
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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) |
19
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From 65 to 84 years |
4
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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 |
Ninety participants were screened and 23 participants were enrolled. | ||||||||||||
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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 | ||||||||||||
Arm description |
Participants received 150 milligrams (mg) erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death. | ||||||||||||
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 oral doses were administered daily.
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Baseline characteristics reporting groups
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Reporting group title |
Erlotinib
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Reporting group description |
Participants received 150 milligrams (mg) erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death. | |||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Erlotinib
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Reporting group description |
Participants received 150 milligrams (mg) erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death. | ||
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End point title |
Progression-Free Survival (PFS), as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) [1] | ||||||||
End point description |
PFS was the time from inclusion in the study to the date of first documented PD or death from any cause, whichever occurred first. Participants without event were censored at the date of the last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Analysis was performed using Kaplan-Meier method. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. All enrolled participants.
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End point type |
Primary
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End point timeframe |
Baseline up to approximately 4 years
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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 analysis was planned in this study. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Time to Disease Progression, as Assessed by Investigator Using RECIST v1.1 | ||||||||
End point description |
Time to disease progression was defined as the time from baseline evaluation to the first date PD was recorded. Participants without progression were censored at the date of last tumor assessment where non-progression was documented. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. All enrolled participants.
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End point type |
Secondary
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End point timeframe |
Baseline up to approximately 4 years
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants with Complete Response (CR) And Partial Response (PR) as Assessed by the Investigator Using RECIST v1.1 | ||||||||||||
End point description |
CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to baseline. All enrolled participants.
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End point type |
Secondary
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End point timeframe |
Baseline up to approximately 4 years
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Participants who Were Alive One Year After Study Treatment Initiation | ||||||||
End point description |
All enrolled participants with available data for this end point.
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End point type |
Secondary
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End point timeframe |
Year 1
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| No statistical analyses for this end point | |||||||||
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End point title |
Percentage of Participants by Localization of PD as Assessed by Investigator Using RECIST v1.1 | ||||||||||||||||||
End point description |
PD was assessed using RECIST v1.1. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Percentage of participants by localization of PD were reported. Localization included: Left lung inferior lobe; Para-aortic; Left lung upper lobe; Right lung inferior lobe; and Infracranial. All enrolled participants with available data for this end point.
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End point type |
Secondary
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End point timeframe |
Baseline up to approximately 4 years
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of EGFR Positive Participants Classified Based on Smoking Status | ||||||||||||||
End point description |
Participants were asked: “Have you smoked at least 100 cigarettes in your entire life?” and “Do you now smoke cigarettes every day, some days, or not at all?” Responses were grouped into three categories: Current Smoker, Former Smoker, and Non-Smoker. Participants who reported smoking at least 100 cigarettes in their lifetime and who, at the time of survey, smoked either every day or some days were defined as 'Current smoker'. Participants who reported smoking at least 100 cigarettes in their lifetime and who, at the time of the survey, did not smoke at all were defined as 'Former smoker'. Participants who reported never having smoked 100 cigarettes were defined as 'Non-smoker'. All enrolled participants.
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End point type |
Secondary
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End point timeframe |
Day 1
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of EGFR Positive Participants Classified Based on Type of EGFR Mutations | ||||||||||||
End point description |
Participants with NSCLC have tumor associated with EGFR mutations. These mutations occur within EGFR Exons 18-21, which encodes a portion of the EGFR kinase domain. All enrolled participants.
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End point type |
Secondary
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End point timeframe |
Day 1
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Percentage of Similar EGFR Mutations Between Matched Plasma and Tumor Tissue Samples | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Baseline up to approximately 4 years
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| Notes [2] - No participants were analyzed for this outcome as no plasma samples during the 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 |
Up to approximately 5 years 4 months
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Adverse event reporting additional description |
Safety analysis population included all participants who receive at least one dose of treatment and had at least one monthly assessment.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
Unspecific
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Reporting groups
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Reporting group title |
Erlotinib
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Reporting group description |
Participants received 150 mg erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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19 Aug 2013 |
Protocol was amended to reduce the number of the enrolled participants, study procedures, adverse events reporting and other modifications. |
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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 | |||
