Clinical Trial Results:
Phase II, open-label study of erlotinib (Tarceva®) treatment in patients with locally advanced, metastatic or recurrent non-small cell lung cancer who present activating mutations in the tyrosine kinase domain of the epidermal growth factor receptor
|
Summary
|
|
EudraCT number |
2010-024061-48 |
Trial protocol |
BG |
Global end of trial date |
10 Jan 2014
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
12 Mar 2016
|
First version publication date |
12 Mar 2016
|
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 |
ML25423
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT01372384 | ||
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 61 6878333, global.trial_information@roche.com
|
||
Scientific contact |
Roche Trial Information Hotline, F. Hoffmann-La Roche AG, +41 61 6878333, 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 |
10 Jan 2014
|
||
Is this the analysis of the primary completion data? |
No
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
10 Jan 2014
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
Evaluate efficacy of erlotinib (Tarceva TM; 150 mg) on progression free survival (PFS) in participants with non-small cell lung cancer (NSCLC) in locally advanced or metastatic stages (Stage IIIB and Stage IV) or recurrent NSCLC 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 |
The conduct of this clinical study met all local legal and regulatory requirements. The study was
conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki
and the International Conference on Harmonization guideline E6: Good Clinical Practice. Before entering the study, the informed consent form was read by and explained to all participants and/or their legally authorized representative. Participants signed informed consent form and could withdraw from the study at any time without any disadvantage and without having to provide a reason for this decision. Only investigators qualified by training and experience were selected as appropriate experts to investigate the study drug.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
06 Jan 2012
|
||
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 |
Bulgaria: 6
|
||
Worldwide total number of subjects |
6
|
||
EEA total number of subjects |
6
|
||
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) |
2
|
||
From 65 to 84 years |
4
|
||
85 years and over |
0
|
||
|
|||||||||||
|
Recruitment
|
|||||||||||
Recruitment details |
- | ||||||||||
|
Pre-assignment
|
|||||||||||
Screening details |
In all, 145 patients were screened. Of these, 6 participants were randomized; major reason for screen failure was negative mutation status. | ||||||||||
|
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
|
|||||||||||
|
Arm title
|
Erlotinib | ||||||||||
Arm description |
Participants received recommended dose of erlotinib (150 mg/day). No dose escalation of erlotinib was permitted. Participants were treated until disease progression, unacceptable toxicity, death or participant request for discontinuation. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Erlotinib
|
||||||||||
Investigational medicinal product code |
|||||||||||
Other name |
|||||||||||
Pharmaceutical forms |
Film-coated tablet
|
||||||||||
Routes of administration |
Oral use
|
||||||||||
Dosage and administration details |
Erlotinib was administered as a single daily oral dose as a Tablet of 150 mg, with up to 200 ml of water,
preferably in the morning. No dose escalation of erlotinib was permitted. The study drug was taken at
least 1 hour before or 2 hours after ingestion of food or any other medication.
|
||||||||||
|
|||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Erlotinib
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received recommended dose of erlotinib (150 mg/day). No dose escalation of erlotinib was permitted. Participants were treated until disease progression, unacceptable toxicity, death or participant request for discontinuation. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Erlotinib
|
||
Reporting group description |
Participants received recommended dose of erlotinib (150 mg/day). No dose escalation of erlotinib was permitted. Participants were treated until disease progression, unacceptable toxicity, death or participant request for discontinuation. | ||
Subject analysis set title |
Intent-to-treat population
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The Intent-to-treat (ITT) population included all participants with at least one valid post-baseline assessment.
|
||
Subject analysis set title |
Per-Protocol population
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
The per-protocol (PP) population included all participants from the ITT population who did not violate the inclusion criteria: Histologically documented inoperable, locally advanced (Stage IIIB with supraclavicular lymph node metastases or malignant pleural or pericardial effusion [if clinically significant – after treatment]) or metastatic (Stage IV) NSCLC or recurrent NSCLC disease who presented with activating mutations (exon 19 deletions or exon 21 substitution L858R) in the tyrosine kinase domain of EGFR.
|
||
Subject analysis set title |
Safety population
|
||
Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All participants who received at least one dose of study drug and had a safety assessment
performed post baseline were included in the safety population. Participants were analyzed according to the first dose received during the study.
|
||
|
|||||||||
End point title |
Progression Free Survival [1] | ||||||||
End point description |
Progression free survival is (PFS) defined as the time from the first dose of erlotinib to the date of first
occurrence of disease progression or death. The ITT population was used for the analysis.
|
||||||||
End point type |
Primary
|
||||||||
End point timeframe |
Until participants had disease progression, unacceptable toxicity or died (approximately 24 months).
|
||||||||
| 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: Primary end point was described using descriptive statistics; no statistical analyses were carried out. |
|||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||
End point title |
Overall survival | ||||||||
End point description |
The overall survival (OS) is defined as the time from the first dose of erlotinib to the date of death due
to any cause. The ITT population was used for the analysis.
|
||||||||
End point type |
Secondary
|
||||||||
End point timeframe |
Until participants had disease progression, unacceptable toxicity, or died (approximately 24 months).
|
||||||||
|
|||||||||
| No statistical analyses for this end point | |||||||||
|
|||||||||||||||||||||||||
End point title |
Objective Response Rate (Investigator Assessed) | ||||||||||||||||||||||||
End point description |
Objective response rate (ORR) was defined by Response evaluation criteria in solid tumors (RECIST) criteria 1.1 : Partial response (PR) was defined as >= 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) was defined as disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression of disease (PD) was defined as 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions. Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on the study. The ITT population was used for the analysis.
|
||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||
End point timeframe |
Visit 4, Visit 6, Visit 10 and Visit 22 (approximately 24 months)
|
||||||||||||||||||||||||
|
|||||||||||||||||||||||||
Attachments |
Statistical Analysis for between proportions of Re |
||||||||||||||||||||||||
| Notes [2] - Only those participants available at the specified time points were analyzed (represented by n=X) |
|||||||||||||||||||||||||
| No statistical analyses for this end point | |||||||||||||||||||||||||
|
|||||||||||
End point title |
Safety: Incidence of Adverse Events | ||||||||||
End point description |
An AE is any untoward medical occurrence in a patient or clinical investigation patient administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. An SAE is any experience that suggests a significant hazard, contraindication, side effect, or precaution. The safety population was used for the analysis.
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
Until participants had disease progression, unacceptable toxicity, or died (approximately 24 months).
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Up to 24 months
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Serious adverse events and non-serious adverse events are reported in Safety Analysis Set, consists of
all participants who received at least one dose of study drug and had a safety assessment
performed post baseline.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Erlotinib
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Participants received recommended dose of erlotinib (150 mg/day). No dose escalation of erlotinib was permitted. Participants were treated until disease progression, unacceptable toxicity, death or participant request for discontinuation. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? No | |||
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 | |||
