Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Study to Assess the Incidence of Mutations in the Tyrosine Kinase Domain of the Epidermal Growth Factor Receptor in UK Patients with Newly Diagnosed Locally Advanced or Metastatic Non-Small Cell Lung Cancer and to Investigate the Quality of Life of These Patients Undergoing First-Line Monotherapy with Erlotinib (Tarceva®).

    Summary
    EudraCT number
    		 2010-021120-96
    Trial protocol
    		 GB  
    Global end of trial date
    07 May 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Feb 2016
    First version publication date
    25 Feb 2016
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ML25279
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01250119
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, CH-4070, Basel, Switzerland,
    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
    14 Jul 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 May 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to assess the prevalence of Epidermal Growth Factor Receptor (EGFR) exon 19 deletion or exon 21 mutation in Non-Small Cell Lung Cancer (NSCLC) participants tested in the United Kingdom (UK).
    Protection of trial subjects
    The study was conducted in full conformance with the principles of the Declaration of Helsinki. The study also adhered to the principles outlined in the Guideline for Good Clinical Practice (GCP) International Conference on Harmonisation (ICH) Tripartite Guideline (January 1977) and with local UK law. The investigators ensured compliance with the European Union (EU) Clinical Trial Directive (2001/20/EC).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    19 May 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 688
    Worldwide total number of subjects
    688
    EEA total number of subjects
    688
    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)
    243
    From 65 to 84 years
    424
    85 years and over
    21

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 During the Diagnostic Phase, Screening period was from Day -28 to Day -14 and during the Treatment Phase, Screening period was from Day -14 to Day -1.

    Period 1
    Period 1 title
    Diagnostic Phase
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Non-Small-Cell Lung Cancer (NSCLC) Group
    Arm description
    		 During the Diagnostic Phase participants newly diagnosed with recurrent or metastatic NSCLC were tested for Epidermal Growth Factor Receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Erlotinib
    Investigational medicinal product code
    Other name
    Tarceva
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Erlotinib was administered on an outpatient basis at a fixed dose of 150 mg as a single daily oral dose.

    Number of subjects in period 1
    		Non-Small-Cell Lung Cancer (NSCLC) Group
    Started
    688
    Completed
    575
    Not completed
    113
         Participants not tested
    44
         Failed to produce a test results
    69
    Period 2
    Period 2 title
    Treatment Phase
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Erlotinib 150 milligrams per day (mg/day)
    Arm description
    		 During the Treatment Phase participants found to have a tumor with EGFR exon 19 deletion or exon 21 (L858R) mutations received erlotinib 150 mg/day as a single oral dose until progressive disease (PD), death, unacceptable toxicity or withdrawal of consent.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Erlotinib
    Investigational medicinal product code
    Other name
    Tarceva
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Erlotinib was administered on an outpatient basis at a fixed dose of 150 mg as a single daily oral dose.

    Number of subjects in period 2 [1]
    		Erlotinib 150 milligrams per day (mg/day)
    Started
    41
    Completed
    0
    Not completed
    41
         Adverse event, serious fatal
    2
         Consent withdrawn by subject
    1
         Adverse event, non-fatal
    2
         Unknown reason
    4
         Progressive disease
    32
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: During the first period (Diagnostic Phase) participants were tested to determine the presence of EGFR exon 19 deletions or exon 21 (L858R) mutations. Only participants who tested positive for exon 19 deletions or exon 21 (L858R) mutations were included in the second period (Treatment Phase). Out of 52 participants with positive EGFR mutation test result, only 41 participants were treated.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Non-Small-Cell Lung Cancer (NSCLC) Group
    Reporting group description
    		 During the Diagnostic Phase participants newly diagnosed with recurrent or metastatic NSCLC were tested for Epidermal Growth Factor Receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations.

    Reporting group values
    		 Non-Small-Cell Lung Cancer (NSCLC) Group Total
    Number of subjects
    		 688 688
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 68 ± 10 -
    Gender categorical
    Units: Subjects
        Female
    		 299 299
        Male
    		 389 389

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Non-Small-Cell Lung Cancer (NSCLC) Group
    Reporting group description
    		 During the Diagnostic Phase participants newly diagnosed with recurrent or metastatic NSCLC were tested for Epidermal Growth Factor Receptor (EGFR) exon 19 deletions or exon 21 (L858R) mutations.
    Reporting group title
    Erlotinib 150 milligrams per day (mg/day)
    Reporting group description
    		 During the Treatment Phase participants found to have a tumor with EGFR exon 19 deletion or exon 21 (L858R) mutations received erlotinib 150 mg/day as a single oral dose until progressive disease (PD), death, unacceptable toxicity or withdrawal of consent.

    Subject analysis set title
    EGFR Positive
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants who tested positive for EGFR mutations were included in this group.

    Subject analysis set title
    EGFR Negative
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    All participants who tested negative for EGFR mutations were included in this group.

    Subject analysis set title
    EGFR Positive and Negative
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants who tested either positive or negative foe EGFR mutations were included in this group.

    Primary: Percentage of Participants Who Tested Positive for EGFR Mutations

    		 Close Top of page
    End point title
    		 Percentage of Participants Who Tested Positive for EGFR Mutations [1]
    End point description
    All participants newly diagnosed with recurrent or metastatic NSCLC were tested for EGFR exon 19 deletion or exon 21 mutations. Diagnostic population: All participants newly diagnosed with recurrent or metastatic NSCLC who entered the study and signed the consent form were included in this population.
    End point type
    Primary
    End point timeframe
    14 days
    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: The primary endpoint in this study was to determine the percentage of participants who test positive for EGFR mutations in the diagnostic phase. Therefore only descriptive analyses were performed for this endpoint.
    End point values
    		 Non-Small-Cell Lung Cancer (NSCLC) Group
    Number of subjects analysed
    644 [2]
    Units: percentage of participants
        number (not applicable)
    8.1
    Notes
    [2] - Only participants who were tested for EGFR mutations were included in the analysis.
    No statistical analyses for this end point

    Primary: Percentage of Participants With EGFR Mutations by Subgroup

    		 Close Top of page
    End point title
    		 Percentage of Participants With EGFR Mutations by Subgroup
    End point description
    Incidence of EGFR mutations were summarized overall and with respect to different subgroups as follows: (1) equals (=) Histopathology, (2) = Stage of disease, (3) = Age at consent, (4) = Gender, (5) = Race, (6) = Smoking history. Only participants with a valid EGFR mutations test result were included in the analysis. Analysis was performed on the Diagnostic Population.
    End point type
    Primary
    End point timeframe
    14 days
    End point values
    		 EGFR Positive EGFR Negative
    Number of subjects analysed
    52
    523
    Units: percentage of participants
    number (not applicable)
        (1) Squamous cell carcinoma
    0
    22.6
        (1) Adenocarcinoma
    100
    67.3
        (1) Bronchoalveolar carcinoma
    0
    1.7
        (1) Large cell carcinoma
    0
    0.6
        (1) Other
    0
    7.8
        (2) Unresectable Stage IIIB
    1.9
    11.9
        (2) Stage IIIB with malignant effusions
    1.9
    3.4
        (2) Stage IV
    96.2
    84.7
        (3) Less than 70 years
    73.1
    55.6
        (3) Greater than 70 years
    26.9
    44.4
        (4) Male
    23.1
    60.8
        (4) Female
    76.9
    39.2
        (5) Asian
    13.5
    2.9
        (5) Black
    9.6
    3.3
        (5) Caucasian
    75
    93.5
        (5) Other
    1.9
    0.4
        (6) Never smoked
    44.2
    7.8
        (6) Previous smoker
    44.2
    60.6
        (6) Current smoker
    7.7
    31
        (6) Missing
    3.8
    0.6
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    EGFR Positive v EGFR Negative
    Number of subjects included in analysis
    575
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0 [3]
    Method
    		 Wald Test
    Confidence interval
    Notes
    [3] - Test for difference in incidence of EGFR mutations for each subgroup controlled for histopathology; Univariate analysis
    Statistical analysis title
    		 Statistical Analysis 2
    Comparison groups
    EGFR Positive v EGFR Negative
    Number of subjects included in analysis
    575
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1038 [4]
    Method
    		 Wald Test
    Confidence interval
    Notes
    [4] - Test for difference in incidence of EGFR mutations for each subgroup controlled for histopathology; Multivariate analysis (6 main effects only).
    Statistical analysis title
    		 Statistical Analysis 3
    Comparison groups
    EGFR Positive v EGFR Negative
    Number of subjects included in analysis
    575
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0588 [5]
    Method
    		 Wald Test
    Confidence interval
    Notes
    [5] - Test for difference in incidence of EGFR mutations for each subgroup controlled for stage of disease; Univariate analysis
    Statistical analysis title
    		 Statistical Analysis 4
    Comparison groups
    EGFR Positive v EGFR Negative
    Number of subjects included in analysis
    575
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.4802 [6]
    Method
    		 Wald Test
    Confidence interval
    Notes
    [6] - Test for difference in incidence of EGFR mutations for each subgroup controlled for stage of disease; Multivariate analysis (6 main effects only).
    Statistical analysis title
    		 Statistical Analysis 5
    Comparison groups
    EGFR Negative v EGFR Positive
    Number of subjects included in analysis
    575
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0147 [7]
    Method
    		 Wald Test
    Confidence interval
    Notes
    [7] - Test for difference in incidence of EGFR mutations for each subgroup controlled for age at consent; Multivariate analysis (6 main effects only).
    Statistical analysis title
    		 Statistical Analysis 6
    Comparison groups
    EGFR Positive v EGFR Negative
    Number of subjects included in analysis
    575
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.1181 [8]
    Method
    		 Wald Test
    Confidence interval
    Notes
    [8] - Test for difference in incidence of EGFR mutations for each subgroup controlled for age at consent; Multivariate analysis (6 main effects only).
    Statistical analysis title
    		 Statistical Analysis 7
    Comparison groups
    EGFR Positive v EGFR Negative
    Number of subjects included in analysis
    575
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0 [9]
    Method
    		 Wald Test
    Confidence interval
    Notes
    [9] - Test for difference in incidence of EGFR mutations for each subgroup controlled for gender; Univariate analysis.
    Statistical analysis title
    		 Statistical Analysis 8
    Comparison groups
    EGFR Positive v EGFR Negative
    Number of subjects included in analysis
    575
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0006 [10]
    Method
    		 Wald Test
    Confidence interval
    Notes
    [10] - Test for difference in incidence of EGFR mutations for each subgroup controlled for gender; Multivariate analysis (6 main effects only).
    Statistical analysis title
    		 Statistical Analysis 9
    Comparison groups
    EGFR Positive v EGFR Negative
    Number of subjects included in analysis
    575
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0004 [11]
    Method
    		 Wald Test
    Confidence interval
    Notes
    [11] - Test for difference in incidence of EGFR mutations for each subgroup controlled for race; Univariate analysis.
    Statistical analysis title
    		 Statistical Analysis 10
    Comparison groups
    EGFR Positive v EGFR Negative
    Number of subjects included in analysis
    575
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.3371 [12]
    Method
    		 Wald Test
    Confidence interval
    Notes
    [12] - Test for difference in incidence of EGFR mutations for each subgroup controlled for race; Multivariate analysis (6 main effects only).
    Statistical analysis title
    		 Statistical Analysis 11
    Comparison groups
    EGFR Positive v EGFR Negative
    Number of subjects included in analysis
    575
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0 [13]
    Method
    		 Wald Test
    Confidence interval
    Notes
    [13] - Test for difference in incidence of EGFR mutations for each subgroup controlled for smoking history; Univariate analysis.
    Statistical analysis title
    		 Statistical Analysis 12
    Comparison groups
    EGFR Positive v EGFR Negative
    Number of subjects included in analysis
    575
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0001 [14]
    Method
    		 Wald Test
    Confidence interval
    Notes
    [14] - Test for difference in incidence of EGFR mutations for each subgroup controlled for smoking history; Multivariate analysis (6 main effects only).

    Secondary: Percentage of Participants With a Response by Best Objective Tumor Response

    		 Close Top of page
    End point title
    		 Percentage of Participants With a Response by Best Objective Tumor Response
    End point description
    Best objective response was defined as the best response recorded from the start of treatment until disease progression/recurrence. Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<)10 millimeters (mm). Partial Response (PR): At least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this may include the baseline sum). The sum must also demonstrate an absolute increase of at least 5 mm. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Intention-to-treat (ITT) population: All participants in the target population who were eligible for treatment and who actually received one dose of treatment.
    End point type
    Secondary
    End point timeframe
    Screening, Day 1 of each 6 week visit starting from Visit 3 until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months
    End point values
    		 Erlotinib 150 milligrams per day (mg/day)
    Number of subjects analysed
    41
    Units: percentage of participants
    number (not applicable)
        CR
    0
        PR
    84.8
        SD
    9.1
        PD
    6.1
    No statistical analyses for this end point

    Secondary: Probability of Being Alive and Free of Progression by Timepoint

    		 Close Top of page
    End point title
    		 Probability of Being Alive and Free of Progression by Timepoint
    End point description
    Progression Free Survival (PFS) was defined as the interval (number of days) from the trial treatment start date to the earlier of the date of the first tumor response assessment of PD or the date of death by any cause. Participants who experienced neither of these events or who were lost to followup at the time of the analysis were censored at date of last contact. PFS was summarized according to the Kaplan-Meier method. Analysis was performed on the ITT Population.
    End point type
    Secondary
    End point timeframe
    Months 0, 3, 6, 9, 12, 15, and 18
    End point values
    		 Erlotinib 150 milligrams per day (mg/day)
    Number of subjects analysed
    41 [15]
    Units: Probability of being alive
    number (confidence interval 95%)
        0 Months
    1 (1 to 1)
        3 Months
    0.97 (0.81 to 1)
        6 Months
    0.94 (0.78 to 0.98)
        9 Months
    0.73 (0.54 to 0.85)
        12 Months
    0.54 (0.36 to 0.69)
        15 Months
    0.37 (0.21 to 0.54)
        18 Months
    0.22 (0.09 to 0.39)
    Notes
    [15] - ITT population
    No statistical analyses for this end point

    Secondary: Survival Time in Months

    		 Close Top of page
    End point title
    		 Survival Time in Months
    End point description
    Duration of time in months from Screening until Death due to any cause. Analysis was performed on the ITT population.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 1 of each 6-week visit starting from Visit 3 until PD, Death, Unacceptable toxicity or Withdrawal of consent
    End point values
    		 Erlotinib 150 milligrams per day (mg/day)
    Number of subjects analysed
    41
    Units: months
        median (confidence interval 95%)
    12.57 (10.1 to 16.53)
    No statistical analyses for this end point

    Secondary: Quality of Life Assessment Using EuroQol(EQ) 5D Visual Analog Score (VAS) Instrument

    		 Close Top of page
    End point title
    		 Quality of Life Assessment Using EuroQol(EQ) 5D Visual Analog Score (VAS) Instrument
    End point description
    he EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The EQ-5D also contains a visual analog scale (EQ-VAS), which records the respondent's self-rated health status on a vertical graduated visual analog scale in millimeters (mm) ranging from 0 (worst imaginable health state) to 100 (best imaginable health state). Analysis was performed on the ITT population.
    End point type
    Secondary
    End point timeframe
    Screening, Baseline and Final or Withdrawal Visit up to 34 months
    End point values
    		 Erlotinib 150 milligrams per day (mg/day)
    Number of subjects analysed
    40 [16]
    Units: mm
    arithmetic mean (standard deviation)
        Screening (n=40)
    62.6 ± 23.5
        Baseline (n=20)
    65.4 ± 19.9
        Final visit/Withdrawal (n=20)
    63 ± 22.4
        Change from Baseline Final visit(n=20)
    -0.4 ± 22
    Notes
    [16] - number (n) = number of participants analyzed at the specified visit.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Problems With Mobility as Assessed Using the EQ-5D

    		 Close Top of page
    End point title
    		 Percentage of Participants With Problems With Mobility as Assessed Using the EQ-5D
    End point description
    The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their mobility as the following categories: Category 1. I have no problems in walking about; Category 2. I have some problems in walking about; Category 3. I am confined to bed. Analysis was performed on the ITT Population.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months
    End point values
    		 Erlotinib 150 milligrams per day (mg/day)
    Number of subjects analysed
    41 [17]
    Units: percentage of participants
    number (not applicable)
        Screening Category 1 (n=41)
    43.9
        Screening Category 2 (n=41)
    56.1
        Screening Category 3 (n=41)
    0
        Visit 01 Category 1 (n=20)
    45
        Visit 01 Category 2 (n=20)
    55
        Visit 01 Category 3 (n=20)
    0
        Visit 02 Category 1 (n=33)
    45.5
        Visit 02 Category 2 (n=33)
    54.5
        Visit 02 Category 3 (n=33)
    0
        Visit 03 Category 1 (n=30)
    56.7
        Visit 03 Category 2 (n=30)
    43.3
        Visit 03 Category 3 (n=30)
    0
        Visit 04 Category 1 (n=29)
    51.7
        Visit 04 Category 2 (n=29)
    48.3
        Visit 04 Category 3 (n=29)
    0
        Visit 05 Category 1 (n=33)
    54.5
        Visit 05 Category 2 (n=33)
    45.5
        Visit 05 Category 3 (n=33)
    0
        Visit 06 Category 1 (n=31)
    54.8
        Visit 06 Category 2 (n=31)
    45.2
        Visit 06 Category 3 (n=31)
    0
        Visit 07 Category 1 (n=29)
    58.6
        Visit 07 Category 2 (n=29)
    41.4
        Visit 07 Category 3 (n=29)
    0
        Visit 08 Category 1 (n=27)
    55.6
        Visit 08 Category 2 (n=27)
    44.4
        Visit 08 Category 3 (n=27)
    0
        Visit 09 Category 1 (n=24)
    62.5
        Visit 09 Category 2 (n=24)
    37.5
        Visit 09 Category 3 (n=24)
    0
        Visit 10 Category 1 (n=21)
    42.9
        Visit 10 Category 2 (n=21)
    57.1
        Visit 10 Category 3 (n=21)
    0
        Visit 11 Category 1 (n=13)
    46.2
        Visit 11 Category 2 (n=13)
    53.8
        Visit 11 Category 3 (n=13)
    0
        Visit 12 Category 1 (n=11)
    45.5
        Visit 12 Category 2 (n=11)
    54.5
        Visit 12 Category 3 (n=11)
    0
        Visit 13 Category 1 (n=9)
    55.6
        Visit 13 Category 2 (n=9)
    44.4
        Visit 13 Category 3 (n=9)
    0
        Visit 14 Category 1 (n=8)
    50
        Visit 14 Category 2 (n=8)
    50
        Visit 14 Category 3 (n=8)
    0
        Visit 15 Category 1 (n=5)
    40
        Visit 15 Category 2 (n=5)
    60
        Visit 15 Category 3 (n=5)
    0
        Visit 16 Category 1 (n=4)
    25
        Visit 16 Category 2 (n=4)
    75
        Visit 16 Category 3 (n=4)
    0
        Visit 17 Category 1 (n=4)
    25
        Visit 17 Category 2 (n=4)
    75
        Visit 17 Category 3 (n=4)
    0
        Visit 18 Category 1 (n=3)
    33.3
        Visit 18 Category 2 (n=3)
    66.7
        Visit 18 Category 3 (n=3)
    0
        Visit 19 Category 1 (n=2)
    50
        Visit 19 Category 2 (n=2)
    50
        Visit 19 Category 3 (n=2)
    0
        Visit 20 Category 1 (n=2)
    50
        Visit 20 Category 2 (n=2)
    50
        Visit 20 Category 3 (n=2)
    0
        Visit 21 Category 1 (n=2)
    50
        Visit 21 Category 2 (n=2)
    50
        Visit 21 Category 3 (n=2)
    0
        Visit 22 Category 1 (n=1)
    0
        Visit 22 Category 2 (n=1)
    100
        Visit 22 Category 3 (n=1)
    0
        Visit 23 Category 1 (n=1)
    0
        Visit 23 Category 2 (n=1)
    100
        Visit 23 Category 3 (n=1)
    0
        Visit 24 Category 1 (n=1)
    0
        Visit 24 Category 2 (n=1)
    100
        Visit 24 Category 3 (n=1)
    0
        Visit 25 Category 1 (n=1)
    0
        Visit 25 Category 2 (n=1)
    100
        Visit 25 Category 3 (n=1)
    0
        Final visit/Withdraw Category 1 (n=21)
    33.3
        Final visit/Withdraw Category 2 (n=21)
    66.7
        Final visit/Withdraw Category 3 (n=21)
    0
    Notes
    [17] - n = number of participants analyzed at for the given parameter at the specified visit.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Problems With Self-Care as Assessed Using the EQ-5D

    		 Close Top of page
    End point title
    		 Percentage of Participants With Problems With Self-Care as Assessed Using the EQ-5D
    End point description
    The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their self-care as the following categories: Category 1. I have no problems with self-care; Category 2. I have some problems washing or dressing myself; Category 3. I am unable to wash or dress myself. Analysis was performed on the ITT Population.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months
    End point values
    		 Erlotinib 150 milligrams per day (mg/day)
    Number of subjects analysed
    41 [18]
    Units: percentage of particvipants
    number (not applicable)
        Screening Category 1 (n=41)
    78
        Screening Category 2 (n=41)
    17.1
        Screening Category 3 (n=41)
    4.9
        Visit 01 Category 1 (n=20)
    80
        Visit 01 Category 2 (n=20)
    20
        Visit 01 Category 3 (n=20)
    0
        Visit 02 Category 1 (n=33)
    81.8
        Visit 02 Category 2 (n=33)
    18.2
        Visit 02 Category 3 (n=33)
    0
        Visit 03 Category 1 (n=29)
    86.2
        Visit 03 Category 2 (n=29)
    13.8
        Visit 03 Category 3 (n=29)
    0
        Visit 04 Category 1 (n=28)
    82.1
        Visit 04 Category 2 (n=28)
    17.9
        Visit 04 Category 3 (n=28)
    0
        Visit 05 Category 1 (n=33)
    78.8
        Visit 05 Category 2 (n=33)
    21.2
        Visit 05 Category 3 (n=33)
    0
        Visit 06 Category 1 (n=31)
    83.9
        Visit 06 Category 2 (n=31)
    16.1
        Visit 06 Category 3 (n=31)
    0
        Visit 07 Category 1 (n=29)
    79.3
        Visit 07 Category 2 (n=29)
    20.7
        Visit 07 Category 3 (n=29)
    0
        Visit 08 Category 1 (n=27)
    85.2
        Visit 08 Category 2 (n=27)
    14.8
        Visit 08 Category 3 (n=27)
    0
        Visit 09 Category 1 (n=24)
    75
        Visit 09 Category 2 (n=24)
    25
        Visit 09 Category 3 (n=24)
    0
        Visit 10 Category 1 (n=21)
    71.4
        Visit 10 Category 2 (n=21)
    28.6
        Visit 10 Category 3 (n=21)
    0
        Visit 11 Category 1 (n=13)
    61.5
        Visit 11 Category 2 (n=13)
    38.5
        Visit 11 Category 3 (n=13)
    0
        Visit 12 Category 1 (n=11)
    54.5
        Visit 12 Category 2 (n=11)
    45.5
        Visit 12 Category 3 (n=11)
    0
        Visit 13 Category 1 (n=9)
    55.6
        Visit 13 Category 2 (n=9)
    44.4
        Visit 13 Category 3 (n=9)
    0
        Visit 14 Category 1 (n=8)
    62.5
        Visit 14 Category 2 (n=8)
    37.5
        Visit 14 Category 3 (n=8)
    0
        Visit 15 Category 1 (n=5)
    40
        Visit 15 Category 2 (n=5)
    60
        Visit 15 Category 3 (n=5)
    0
        Visit 16 Category 1 (n=4)
    50
        Visit 16 Category 2 (n=4)
    50
        Visit 16 Category 3 (n=4)
    0
        Visit 17 Category 1 (n=4)
    50
        Visit 17 Category 2 (n=4)
    50
        Visit 17 Category 3 (n=4)
    0
        Visit 18 Category 1 (n=3)
    33.3
        Visit 18 Category 2 (n=3)
    66.7
        Visit 18 Category 3 (n=3)
    0
        Visit 19 Category 1 (n=2)
    50
        Visit 19 Category 2 (n=2)
    50
        Visit 19 Category 3 (n=2)
    0
        Visit 20 Category 1 (n=2)
    50
        Visit 20 Category 2 (n=2)
    50
        Visit 20 Category 3 (n=2)
    0
        Visit 21 Category 1 (n=2)
    50
        Visit 21 Category 2 (n=2)
    50
        Visit 21 Category 3 (n=2)
    0
        Visit 22 Category 1 (n=1)
    100
        Visit 22 Category 2 (n=1)
    0
        Visit 22 Category 3 (n=1)
    0
        Visit 23 Category 1 (n=1)
    0
        Visit 23 Category 2 (n=1)
    100
        Visit 23 Category 3 (n=1)
    0
        Visit 24 Category 1 (n=1)
    0
        Visit 24 Category 2 (n=1)
    100
        Visit 24 Category 3 (n=1)
    0
        Visit 25 Category 1 (n=1)
    0
        Visit 25 Category 2 (n=1)
    100
        Visit 25 Category 3 (n=1)
    0
        Final Visit/Withdraw Category 1 (n=21)
    66.7
        Final Visit/Withdraw Category 2 (n=21)
    33.3
        Final Visit/Withdraw Category 3 (n=21)
    0
    Notes
    [18] - n = number of participants analyzed for the given parameter at the specified visit.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Problems With Usual Activities as Assessed Using the EQ-5D

    		 Close Top of page
    End point title
    		 Percentage of Participants With Problems With Usual Activities as Assessed Using the EQ-5D
    End point description
    The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their ability to perform usual activities as the following categories: Category 1. I have no problems with performing my usual activities; Category 2. I have some problems with performing my usual activities; Category 3. I am unable to perform my usual activities. Analysis was performed on the ITT Population.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months
    End point values
    		 Erlotinib 150 milligrams per day (mg/day)
    Number of subjects analysed
    41 [19]
    Units: percentage of psarticipants
    number (not applicable)
        Screening Category 1 (n=41)
    39
        Screening Category 2 (n=41)
    46.3
        Screening Category 3 (n=41)
    14.6
        Visit 01 Category 1 (n=20)
    40
        Visit 01 Category 2 (n=20)
    50
        Visit 01 Category 3 (n=20)
    10
        Visit 02 Category 1 (n=33)
    36.4
        Visit 02 Category 2 (n=33)
    60.6
        Visit 02 Category 3 (n=33)
    3
        Visit 03 Category 1 (n=30)
    40
        Visit 03 Category 2 (n=30)
    53.3
        Visit 03 Category 3 (n=30)
    6.7
        Visit 04 Category 1 (n=29)
    51.7
        Visit 04 Category 2 (n=29)
    44.8
        Visit 04 Category 3 (n=29)
    3.4
        Visit 05 Category 1 (n=33)
    51.5
        Visit 05 Category 2 (n=33)
    48.5
        Visit 05 Category 3 (n=33)
    0
        Visit 06 Category 1 (n=31)
    45.2
        Visit 06 Category 2 (n=31)
    54.8
        Visit 06 Category 3 (n=31)
    0
        Visit 07 Category 1 (n=29)
    48.3
        Visit 07 Category 2 (n=29)
    51.7
        Visit 07 Category 3 (n=29)
    0
        Visit 08 Category 1 (n=27)
    40.7
        Visit 08 Category 2 (n=27)
    59.3
        Visit 08 Category 3 (n=27)
    0
        Visit 09 Category 1 (n=24)
    33.3
        Visit 09 Category 2 (n=24)
    66.7
        Visit 09 Category 3 (n=24)
    0
        Visit 10 Category 1 (n=21)
    38.1
        Visit 10 Category 2 (n=21)
    61.9
        Visit 10 Category 3 (n=21)
    0
        Visit 11 Category 1 (n=13)
    30.8
        Visit 11 Category 2 (n=13)
    69.2
        Visit 11 Category 3 (n=13)
    0
        Visit 12 Category 1 (n=11)
    27.3
        Visit 12 Category 2 (n=11)
    72.7
        Visit 12 Category 3 (n=11)
    0
        Visit 13 Category 1 (n=9)
    22.2
        Visit 13 Category 2 (n=9)
    77.8
        Visit 13 Category 3 (n=9)
    0
        Visit 14 Category 1 (n=8)
    37.5
        Visit 14 Category 2 (n=8)
    62.5
        Visit 14 Category 3 (n=8)
    0
        Visit 15 Category 1 (n=5)
    20
        Visit 15 Category 2 (n=5)
    80
        Visit 15 Category 3 (n=5)
    0
        Visit 16 Category 1 (n=4)
    25
        Visit 16 Category 2 (n=4)
    75
        Visit 16 Category 3 (n=4)
    0
        Visit 17 Category 1 (n=4)
    25
        Visit 17 Category 2 (n=4)
    75
        Visit 17 Category 3 (n=4)
    0
        Visit 18 Category 1 (n=3)
    33.3
        Visit 18 Category 2 (n=3)
    66.7
        Visit 18 Category 3 (n=3)
    0
        Visit 19 Category 1 (n=2)
    50
        Visit 19 Category 2 (n=2)
    50
        Visit 19 Category 3 (n=2)
    0
        Visit 20 Category 1 (n=2)
    50
        Visit 20 Category 2 (n=2)
    50
        Visit 20 Category 3 (n=2)
    0
        Visit 21 Category 1 (n=2)
    50
        Visit 21 Category 2 (n=2)
    50
        Visit 21 Category 3 (n=2)
    0
        Visit 22 Category 1 (n=1)
    0
        Visit 22 Category 2 (n=1)
    100
        Visit 22 Category 3 (n=1)
    0
        Visit 23 Category 1 (n=1)
    0
        Visit 23 Category 2 (n=1)
    100
        Visit 23 Category 3 (n=1)
    0
        Visit 24 Category 1 (n=1)
    0
        Visit 24 Category 2 (n=1)
    100
        Visit 24 Category 3 (n=1)
    0
        Visit 25 Category 1 (n=1)
    0
        Visit 25 Category 2 (n=1)
    100
        Visit 25 Category 3 (n=1)
    0
        Final Visit/Withdrawal Category 1 (n=21)
    33.3
        Final Visit/Withdrawal Category 2 (n=21)
    61.9
        Final Visit/Withdrawal Category 3 (n=21)
    4.8
    Notes
    [19] - n = number of participants analyzed for the given parameter at the specified visit.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Pain/Discomfort as Assessed Using the EQ-5D

    		 Close Top of page
    End point title
    		 Percentage of Participants With Pain/Discomfort as Assessed Using the EQ-5D
    End point description
    The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their pain as the following categories: Category 1. I have no pain or discomfort; Category 2. I have moderate pain or discomfort; Category 3. I have extreme pain or discomfort. Analysis was performed on the ITT Population.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months
    End point values
    		 Erlotinib 150 milligrams per day (mg/day)
    Number of subjects analysed
    41 [20]
    Units: percentage of participants
    number (not applicable)
        Screening Category 1 (n=41)
    29.3
        Screening Category 2 (n=41)
    63.4
        Screening Category 3 (n=41)
    7.3
        Visit 01 Category 1 (n=20)
    10
        Visit 01 Category 2 (n=20)
    85
        Visit 01 Category 3 (n=20)
    5
        Visit 02 Category 1 (n=32)
    43.8
        Visit 02 Category 2 (n=32)
    56.3
        Visit 02 Category 3 (n=32)
    0
        Visit 03 Category 1 (n=30)
    40
        Visit 03 Category 2 (n=30)
    60
        Visit 03 Category 3 (n=30)
    0
        Visit 04 Category 1 (n=29)
    55.2
        Visit 04 Category 2 (n=29)
    37.9
        Visit 04 Category 3 (n=29)
    6.9
        Visit 05 Category 1 (n=33)
    45.5
        Visit 05 Category 2 (n=33)
    51.5
        Visit 05 Category 3 (n=33)
    3
        Visit 06 Category 1 (n=31)
    48.4
        Visit 06 Category 2 (n=31)
    51.6
        Visit 06 Category 3 (n=31)
    0
        Visit 07 Category 1 (n=29)
    48.3
        Visit 07 Category 2 (n=29)
    51.7
        Visit 07 Category 3 (n=29)
    0
        Visit 08 Category 1 (n=27)
    37
        Visit 08 Category 2 (n=27)
    59.3
        Visit 08 Category 3 (n=27)
    3.7
        Visit 09 Category 1 (n=24)
    50
        Visit 09 Category 2 (n=24)
    37.5
        Visit 09 Category 3 (n=24)
    12.5
        Visit 10 Category 1 (n=21)
    42.9
        Visit 10 Category 2 (n=21)
    47.6
        Visit 10 Category 3 (n=21)
    9.5
        Visit 11 Category 1 (n=13)
    46.2
        Visit 11 Category 2 (n=13)
    53.8
        Visit 11 Category 3 (n=13)
    0
        Visit 12 Category 1 (n=11)
    45.5
        Visit 12 Category 2 (n=11)
    36.4
        Visit 12 Category 3 (n=11)
    18.2
        Visit 13 Category 1 (n=9)
    44.4
        Visit 13 Category 2 (n=9)
    55.6
        Visit 13 Category 3 (n=9)
    0
        Visit 14 Category 1 (n=8)
    62.5
        Visit 14 Category 2 (n=8)
    37.5
        Visit 14 Category 3 (n=8)
    0
        Visit 15 Category 1 (n=5)
    60
        Visit 15 Category 2 (n=5)
    40
        Visit 15 Category 3 (n=5)
    0
        Visit 16 Category 1 (n=4)
    25
        Visit 16 Category 2 (n=4)
    75
        Visit 16 Category 3 (n=4)
    0
        Visit 17 Category 1 (n=4)
    25
        Visit 17 Category 2 (n=4)
    75
        Visit 17 Category 3 (n=4)
    0
        Visit 18 Category 1 (n=3)
    0
        Visit 18 Category 2 (n=3)
    100
        Visit 18 Category 3 (n=3)
    0
        Visit 19 Category 1 (n=2)
    0
        Visit 19 Category 2 (n=2)
    100
        Visit 19 Category 3 (n=2)
    0
        Visit 20 Category 1 (n=2)
    0
        Visit 20 Category 2 (n=2)
    100
        Visit 20 Category 3 (n=2)
    0
        Visit 21 Category 1 (n=2)
    0
        Visit 21 Category 2 (n=2)
    100
        Visit 21 Category 3 (n=2)
    0
        Visit 22 Category 1 (n=1)
    100
        Visit 22 Category 2 (n=1)
    0
        Visit 22 Category 3 (n=1)
    0
        Visit 23 Category 1 (n=1)
    0
        Visit 23 Category 2 (n=1)
    100
        Visit 23 Category 3 (n=1)
    0
        Visit 24 Category 1 (n=1)
    0
        Visit 24 Category 2 (n=1)
    100
        Visit 24 Category 3 (n=1)
    0
        Visit 25 Category 1 (n=1)
    0
        Visit 25 Category 2 (n=1)
    100
        Visit 25 Category 3 (n=1)
    0
        Final Visit/Withdrawal Category 1 (n=21)
    38.1
        Final Visit/Withdrawal Category 2 (n=21)
    57.1
        Final Visit/Withdrawal Category 3 (n=21)
    4.8
    Notes
    [20] - n = number of participants analyzed for the given parameter at the specified visit.
    No statistical analyses for this end point

    Secondary: Percentage of Participants With Anxiety/Depression as Assessed Using the EQ-5D

    		 Close Top of page
    End point title
    		 Percentage of Participants With Anxiety/Depression as Assessed Using the EQ-5D
    End point description
    The EQ-5D contains a descriptive system which measures 5 health dimensions: mobility, self-care, usual activity, pain/discomfort, and anxiety/depression. The participants were required to rate their pain as the following categories: Category 1. I am not anxious or depressed; Category 2. I am moderately anxious or depressed; Category 3. I am extremely anxious or depressed. Analysis was performed on the ITT Population.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 1), Days 10 to 14 (Visit 2), Day 1 of every 6 weeks until PD, Death, Unacceptable toxicity or Withdrawal of consent up to 34 months
    End point values
    		 Erlotinib 150 milligrams per day (mg/day)
    Number of subjects analysed
    41 [21]
    Units: percentage of participants
    number (not applicable)
        Screening Category 1 (n=40)
    52.5
        Screening Category 2 (n=40)
    37.5
        Screening Category 3 (n=40)
    10
        Visit 01 Category 1 (n=19)
    57.9
        Visit 01 Category 2 (n=19)
    42.1
        Visit 01 Category 3 (n=19)
    0
        Visit 02 Category 1 (n=33)
    57.6
        Visit 02 Category 2 (n=33)
    42.4
        Visit 02 Category 3 (n=33)
    0
        Visit 03 Category 1 (n=30)
    43.3
        Visit 03 Category 2 (n=30)
    56.7
        Visit 03 Category 3 (n=30)
    0
        Visit 04 Category 1 (n=29)
    58.6
        Visit 04 Category 2 (n=29)
    41.4
        Visit 04 Category 3 (n=29)
    0
        Visit 05 Category 1 (n=33)
    60.6
        Visit 05 Category 2 (n=33)
    36.4
        Visit 05 Category 3 (n=33)
    3
        Visit 06 Category 1 (n=31)
    48.4
        Visit 06 Category 2 (n=31)
    51.6
        Visit 06 Category 3 (n=31)
    0
        Visit 07 Category 1 (n=29)
    62.1
        Visit 07 Category 2 (n=29)
    37.9
        Visit 07 Category 3 (n=29)
    0
        Visit 08 Category 1 (n=27)
    55.6
        Visit 08 Category 2 (n=27)
    44.4
        Visit 08 Category 3 (n=27)
    0
        Visit 09 Category 1 (n=24)
    62.5
        Visit 09 Category 2 (n=24)
    25
        Visit 09 Category 3 (n=24)
    12.5
        Visit 10 Category 1 (n=21)
    61.9
        Visit 10 Category 2 (n=21)
    28.6
        Visit 10 Category 3 (n=21)
    9.5
        Visit 11 Category 1 (n=13)
    61.5
        Visit 11 Category 2 (n=13)
    30.8
        Visit 11 Category 3 (n=13)
    7.7
        Visit 12 Category 1 (n=11)
    45.5
        Visit 12 Category 2 (n=11)
    45.5
        Visit 12 Category 3 (n=11)
    9.1
        Visit 13 Category 1 (n=9)
    77.8
        Visit 13 Category 2 (n=9)
    22.2
        Visit 13 Category 3 (n=9)
    0
        Visit 14 Category 1 (n=8)
    75
        Visit 14 Category 2 (n=8)
    25
        Visit 14 Category 3 (n=8)
    0
        Visit 15 Category 1 (n=5)
    60
        Visit 15 Category 2 (n=5)
    40
        Visit 15 Category 3 (n=5)
    0
        Visit 16 Category 1 (n=4)
    75
        Visit 16 Category 2 (n=4)
    25
        Visit 16 Category 3 (n=4)
    0
        Visit 17 Category 1 (n=4)
    75
        Visit 17 Category 2 (n=4)
    25
        Visit 17 Category 3 (n=4)
    0
        Visit 18 Category 1 (n=3)
    66.7
        Visit 18 Category 2 (n=3)
    33.3
        Visit 18 Category 3 (n=3)
    0
        Visit 19 Category 1 (n=2)
    50
        Visit 19 Category 2 (n=2)
    50
        Visit 19 Category 3 (n=2)
    0
        Visit 20 Category 1 (n=2)
    50
        Visit 20 Category 2 (n=2)
    50
        Visit 20 Category 3 (n=2)
    0
        Visit 21 Category 1 (n=2)
    50
        Visit 21 Category 2 (n=2)
    50
        Visit 21 Category 3 (n=2)
    0
        Visit 22 Category 1 (n=1)
    100
        Visit 22 Category 2 (n=1)
    0
        Visit 22 Category 3 (n=1)
    0
        Visit 23 Category 1 (n=1)
    0
        Visit 23 Category 2 (n=1)
    100
        Visit 23 Category 3 (n=1)
    0
        Visit 24 Category 1 (n=1)
    0
        Visit 24 Category 2 (n=1)
    100
        Visit 24 Category 3 (n=1)
    0
        Visit 25 Category 1 (n=1)
    0
        Visit 25 Category 2 (n=1)
    100
        Visit 25 Category 3 (n=1)
    0
        Final Visit/Withdrawal Category 1 (n=21)
    57.1
        Final Visit/Withdrawal Category 2 (n=21)
    38.1
        Final Visit/Withdrawal Category 3 (n=21)
    4.8
    Notes
    [21] - n = number of participants analyzed for the given parameter at the specified visit.
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were recorded from Visit 1 (Baseline) until 30 days after the Final/Withdrawal Visit.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    14.1
    Reporting groups
    Reporting group title
    Erlotinib
    Reporting group description
    		 During the Treatment Phase participants found to have a tumour with EGFR exon 19 deletion or exon 21 (L858R) mutations received erlotinib 150 mg/day as a single oral dose until PD, death, unacceptable toxicity or withdrawal of consent.

    Serious adverse events
    		 Erlotinib
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 41 (39.02%)
         number of deaths (all causes)
    9
         number of deaths resulting from adverse events
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Presyncope
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    2 / 41 (4.88%)
         occurrences causally related to treatment / all
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 41 (4.88%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Interstitial lung disease
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Respiratory failure
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Erlotinib
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    40 / 41 (97.56%)
    Investigations
    Pulmonary function test decreased
         subjects affected / exposed
    6 / 41 (14.63%)
         occurrences all number
    8
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    4 / 41 (9.76%)
         occurrences all number
    4
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    7 / 41 (17.07%)
         occurrences all number
    9
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 41 (9.76%)
         occurrences all number
    4
    Chest pain
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    3
    Fatigue
         subjects affected / exposed
    14 / 41 (34.15%)
         occurrences all number
    17
    Mucosal inflammation
         subjects affected / exposed
    6 / 41 (14.63%)
         occurrences all number
    6
    Oedema peripheral
         subjects affected / exposed
    7 / 41 (17.07%)
         occurrences all number
    10
    Pain
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    3
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    4
    Dry eye
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    3
    Vision blurred
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    3
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    5 / 41 (12.20%)
         occurrences all number
    5
    Abdominal pain upper
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    3
    Constipation
         subjects affected / exposed
    9 / 41 (21.95%)
         occurrences all number
    10
    Diarrhoea
         subjects affected / exposed
    26 / 41 (63.41%)
         occurrences all number
    40
    Dyspepsia
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    3
    Nausea
         subjects affected / exposed
    11 / 41 (26.83%)
         occurrences all number
    14
    Oral pain
         subjects affected / exposed
    5 / 41 (12.20%)
         occurrences all number
    5
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    10 / 41 (24.39%)
         occurrences all number
    11
    Dyspnoea
         subjects affected / exposed
    5 / 41 (12.20%)
         occurrences all number
    7
    Epistaxis
         subjects affected / exposed
    5 / 41 (12.20%)
         occurrences all number
    5
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    9 / 41 (21.95%)
         occurrences all number
    9
    Dermatitis acneiform
         subjects affected / exposed
    5 / 41 (12.20%)
         occurrences all number
    5
    Dry skin
         subjects affected / exposed
    13 / 41 (31.71%)
         occurrences all number
    15
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    8
    Pruritus
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    3
    Rash
         subjects affected / exposed
    26 / 41 (63.41%)
         occurrences all number
    42
    Skin ulcer
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    3
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    7 / 41 (17.07%)
         occurrences all number
    7
    Back pain
         subjects affected / exposed
    6 / 41 (14.63%)
         occurrences all number
    8
    Muscle spasms
         subjects affected / exposed
    4 / 41 (9.76%)
         occurrences all number
    5
    Musculoskeletal pain
         subjects affected / exposed
    4 / 41 (9.76%)
         occurrences all number
    4
    Pain in extremity
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    5
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    3
    Lower respiratory tract infection
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    3
    Nasopharyngitis
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    3
    Paronychia
         subjects affected / exposed
    8 / 41 (19.51%)
         occurrences all number
    9
    Urinary tract infection
         subjects affected / exposed
    3 / 41 (7.32%)
         occurrences all number
    3
    Oral candidiasis
         subjects affected / exposed
    4 / 41 (9.76%)
         occurrences all number
    4
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    10 / 41 (24.39%)
         occurrences all number
    10

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    04 Apr 2011
    This amendment clarified that participants with previous treatment with NSCLC with chemotherapy were not excluded if the chemotherapy was neo-adjuvant or adjuvant and was completed > 6 months prior to concent for the diagnostic phase of the study. Physical examination, vital signs and EQ-5D were added to the text on the 'final visit/withdrawal from study' assessments to make the text consistent with the table of assessments. Shelf life of erlotinib was updated to 4 years. RECIST criteria to be used was updated from version 1.0 to 1.1.
    28 Nov 2012
    A further approved indication for erlotinib was added. Introduction sections were updated to included additional publications. Administrative changes were documented. Number of participants to enter diagnostic phase was reduced from 1200 to 700. Number of participants to enter treatment phase was reduced from 120 to 60. It was specified that if the drug was to be destroyed it had to be done by a Roche approved vendor.

    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
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri Apr 26 21:27:25 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA