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   43861   clinical trials with a EudraCT protocol, of which   7284   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 prospective double-blind randomized Phase III study of 300 mg vs. 150 mg erlotinib in current smokers with locally advanced or metastatic NSCLC in second-line setting after failure on chemotherapy

    Summary
    EudraCT number
    		 2010-018476-24
    Trial protocol
    		 NL   ES   DE   DK  
    Global end of trial date
    07 Feb 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    25 Apr 2016
    First version publication date
    08 Aug 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MO22162
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01183858
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    F. Hoffmann-La Roche AG
    Sponsor organisation address
    Grenzacherstrasse 124, Basel, Switzerland, CH-4070
    Public contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Scientific contact
    Roche Trial Information Hotline, F. Hoffmann-La Roche AG, 41 616878333, global.trial_information@roche.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Oct 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Oct 2013
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Feb 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To compare the efficacy of two dose levels of erlotinib (150 mg and 300 mg) on progression-free survival (PFS) in current smokers with stage IIIB/IV NSCLC after failure of first-line platinum-based chemotherapy.
    Protection of trial subjects
    All study participants were required to read and sign an Informed Consent Form. Patients received full supportive care throughout the study, including transfusion of blood products, treatment with antibiotics, anti-emetics, anti-diarrheals, and analgesics as appropriate.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Oct 2010
    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
    Netherlands: 11
    Country: Number of subjects enrolled
    Spain: 29
    Country: Number of subjects enrolled
    Denmark: 12
    Country: Number of subjects enrolled
    France: 19
    Country: Number of subjects enrolled
    Germany: 97
    Country: Number of subjects enrolled
    China: 95
    Country: Number of subjects enrolled
    Egypt: 11
    Country: Number of subjects enrolled
    Switzerland: 5
    Country: Number of subjects enrolled
    Turkey: 34
    Worldwide total number of subjects
    313
    EEA total number of subjects
    168
    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)
    217
    From 65 to 84 years
    96
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 315 participants were randomized. 313 participants were included in the Intent-to -treat (ITT) population. The ITT population excluded 2 randomized participants: 1 participant randomized in error and 1 participant with missing source data.

    Pre-assignment period milestones
    Number of subjects started
    		 315 [1]
    Number of subjects completed
    		 313

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Randomized in error: 1
    Reason: Number of subjects
    		 Missing Source Documentation: 1
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: The worldwide number of 313 participants is based on the Intent-to -treat (ITT)population. The ITT population excluded 2 randomized participants: 1 participant randomized in error and 1 participant with missing source data who are included in the Pre-Assignment period.
    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Erlotinib 150 mg
    Arm description
    		 Erlotinib 150 mg single daily oral dose until disease progression.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Erlotinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Single daily oral dose.

    Arm title
    		 Erlotinib 300 mg
    Arm description
    		 Erlotinib 300 mg single daily oral dose until disease progression.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Erlotinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Single daily oral dose.

    Number of subjects in period 1
    		Erlotinib 150 mg Erlotinib 300 mg
    Started
    154
    159
    Intent-to-treat Population
    154
    159
    Safety Population
    154
    158
    Completed
    1
    3
    Not completed
    153
    156
         Discontinued Smoking
    3
    1
         Withdrew Consent
    4
    4
         Death not related to PD
    5
    6
         Investigator's Decision
    -
    3
         Refused Treatment
    1
    4
         Progressive Disease
    112
    115
         Other Protocol Violation
    1
    -
         Death related to Progressive Disease (PD)
    4
    5
         Adverse Event(s)
    14
    11
         Administrative/Other
    6
    6
         Lost to follow-up
    1
    1
         Insufficient Therapeutic Response
    2
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Erlotinib 150 mg
    Reporting group description
    		 Erlotinib 150 mg single daily oral dose until disease progression.

    Reporting group title
    Erlotinib 300 mg
    Reporting group description
    		 Erlotinib 300 mg single daily oral dose until disease progression.

    Reporting group values
    		 Erlotinib 150 mg Erlotinib 300 mg Total
    Number of subjects
    		 154 159 313
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 106 111 217
        From 65-84 years
    		 48 48 96
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 59.7 ( 9.25 ) 59.2 ( 9.14 ) -
    Gender categorical
    Units: Subjects
        Female
    		 34 35 69
        Male
    		 120 124 244

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Erlotinib 150 mg
    Reporting group description
    		 Erlotinib 150 mg single daily oral dose until disease progression.

    Reporting group title
    Erlotinib 300 mg
    Reporting group description
    		 Erlotinib 300 mg single daily oral dose until disease progression.

    Primary: Progression-Free Survival (PFS)

    		 Close Top of page
    End point title
    		 Progression-Free Survival (PFS)
    End point description
    PFS is defined as the time from randomization to the date of first occurrence of disease progression or death. For target lesions, Progressive Disease (PD) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.
    End point type
    Primary
    End point timeframe
    Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)
    End point values
    		 Erlotinib 150 mg Erlotinib 300 mg
    Number of subjects analysed
    154
    159
    Units: weeks
        median (confidence interval 95%)
    6.86 (6.29 to 12)
    7 (6.29 to 11)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Erlotinib 150 mg v Erlotinib 300 mg
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.671 [1]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1.33
    Notes
    [1] - Unstratified analysis.

    Primary: Progression-Free Survival at the End of Study

    		 Close Top of page
    End point title
    		 Progression-Free Survival at the End of Study
    End point description
    PFS is defined as the time from randomization to the date of first occurrence of disease progression or death. For target lesions, Progressive Disease (PD) was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter recorded since treatment started or the appearance of 1 or more new lesions. For non-target lesions, PD was defined as the appearance of 1 or more new lesions and/or unequivocal progression of existing non-target lesions Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.
    End point type
    Primary
    End point timeframe
    Randomization to End of Study: 14 October 2010 – 7 February 2014 (Up to 39.8 months)
    End point values
    		 Erlotinib 150 mg Erlotinib 300 mg
    Number of subjects analysed
    154
    159
    Units: weeks
        median (confidence interval 95%)
    6.86 (6.29 to 12)
    7 (6.29 to 11.43)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    Erlotinib 300 mg v Erlotinib 150 mg
    Number of subjects included in analysis
    313
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.625 [2]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.06
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.84
         upper limit
    		 1.33
    Notes
    [2] - Unstratified Analysis

    Secondary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point description
    OS defined as the time from randomization to the date of death due to any cause. Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.
    End point type
    Secondary
    End point timeframe
    Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)
    End point values
    		 Erlotinib 150 mg Erlotinib 300 mg
    Number of subjects analysed
    154
    159
    Units: months
        median (confidence interval 95%)
    6.77 (5.65 to 8.77)
    6.83 (5.39 to 8.48)
    No statistical analyses for this end point

    Secondary: Overall Response Rate (ORR)

    		 Close Top of page
    End point title
    		 Overall Response Rate (ORR)
    End point description
    Tumor response was assessed by the investigator using computer tomography (CT) or magnetic resonance imaging (MRI) scans according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A participant was defined as a responder if they sustained a complete response (CR) or partial response (PR) for at least 4 weeks during randomized treatment (confirmed response). Patients with no tumor assessment after the start of study treatment were to be considered as non-responders. The percentage of participants in each best response category is presented. Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.
    End point type
    Secondary
    End point timeframe
    Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)
    End point values
    		 Erlotinib 150 mg Erlotinib 300 mg
    Number of subjects analysed
    154
    159
    Units: participants
    number (confidence interval 95%)
        Complete Response
    0 (0 to 0)
    0 (0 to 0)
        Partial Response
    7.1 (3.6 to 12.4)
    2.5 (0.7 to 6.3)
        Stable Disease
    33.1 (25.8 to 41.1)
    34 (26.6 to 41.9)
        Progressive Disease
    44.8 (36.8 to 53)
    45.9 (38 to 54)
        Not Evaluable
    14.9 (9.7 to 21.6)
    17.6 (12 to 24.4)
    No statistical analyses for this end point

    Secondary: Disease Control Rate (DCR)

    		 Close Top of page
    End point title
    		 Disease Control Rate (DCR)
    End point description
    Tumor response was assessed by the investigator using computer tomography (CT) or magnetic resonance imaging (MRI) scans. Disease control rates were measured according to RECIST version 1.1 criteria. A participant was defined as having controlled disease if they sustained a Complete Response (CR) or Partial Response (PR) for at least 4 weeks during randomized treatment (confirmed response), or Stable Disease (SD) for at least 6 weeks. Patients with no tumor assessment after the start of study treatment were considered as having uncontrolled disease. The percentage of participants with Disease Control is presented. Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.
    End point type
    Secondary
    End point timeframe
    Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)
    End point values
    		 Erlotinib 150 mg Erlotinib 300 mg
    Number of subjects analysed
    154
    159
    Units: percentage of participants
        number (confidence interval 95%)
    40.3 (32.4 to 48.5)
    36.5 (29 to 44.5)
    No statistical analyses for this end point

    Secondary: Time to Progression (TTP)

    		 Close Top of page
    End point title
    		 Time to Progression (TTP)
    End point description
    Tumor response was assessed by the investigator using computer tomography (CT) or magnetic resonance imaging (MRI) scans according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. Time to progression (TTP) in weeks was defined as the time from randomization to the date of disease progression. Participants without event were censored at the date of the last tumor assessment when the patient was known to be progression free. Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.
    End point type
    Secondary
    End point timeframe
    Randomization to Clinical Cutoff: 28 October 2013 (Up to 36.5 months)
    End point values
    		 Erlotinib 150 mg Erlotinib 300 mg
    Number of subjects analysed
    154
    159
    Units: weeks
        median (confidence interval 95%)
    9.86 (6.43 to 12.14)
    9.14 (6.43 to 12)
    No statistical analyses for this end point

    Secondary: Number of Participants With Adverse Events (AEs) at the End of the Study

    		 Close Top of page
    End point title
    		 Number of Participants With Adverse Events (AEs) at the End of the Study
    End point description
    An adverse event was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events. A serious adverse event is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant. Adverse Events in the following categories are presented: Adverse Events, Serious Adverse Events, AEs leading to withdrawal from treatment and AEs leading to death. Safety population included all randomized participants who received at least one dose of study drug.
    End point type
    Secondary
    End point timeframe
    Randomization to End of Study: 14 October 2010 – 7 February 2014 (Up to 39.8 months)
    End point values
    		 Erlotinib 150 mg Erlotinib 300 mg
    Number of subjects analysed
    154
    158
    Units: participants
        Adverse Events (AEs)
    130
    141
        Serious Adverse Events
    29
    35
        AEs leading to withdrawal
    18
    15
        AEs leading to death
    12
    13
    No statistical analyses for this end point

    Secondary: Overall Survival (OS) at the End of Study

    		 Close Top of page
    End point title
    		 Overall Survival (OS) at the End of Study
    End point description
    OS defined as the time from randomization to the date of death due to any cause. Intent-to-treat Population included all randomized participants. 2 participants were excluded from analysis: 1 participant randomized in error and 1 participant with missing source data.
    End point type
    Secondary
    End point timeframe
    Randomization to End of Study: 14 October 2010 – 7 February 2014 (Up to 39.8 months)
    End point values
    		 Erlotinib 150 mg Erlotinib 300 mg
    Number of subjects analysed
    154
    159
    Units: months
        median (confidence interval 95%)
    7 (5.65 to 8.84)
    6.9 (5.62 to 8.64)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Randomization to End of Study: 14 October 2010 – 7 February 2014 (Up to 39.8 months)
    Adverse event reporting additional description
    Safety population: All participants who received at least 1 dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.1
    Reporting groups
    Reporting group title
    Erlotinib 150 mg
    Reporting group description
    		 Erlotinib 150 mg single daily oral dose until disease progression.

    Reporting group title
    Erlotinib 300 mg
    Reporting group description
    		 Erlotinib 300 mg single daily oral dose until disease progression.

    Serious adverse events
    		 Erlotinib 150 mg Erlotinib 300 mg
    Total subjects affected by serious adverse events
         subjects affected / exposed
    29 / 154 (18.83%)
    35 / 158 (22.15%)
         number of deaths (all causes)
    123
    125
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Gastric cancer
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pericardial effusion malignant
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    1 / 154 (0.65%)
    3 / 158 (1.90%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Fatigue
         subjects affected / exposed
    1 / 154 (0.65%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    3 / 154 (1.95%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 154 (0.00%)
    2 / 158 (1.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Acute respiratory failure
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hydropneumothorax
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pulmonary haemorrhage
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hip fracture
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
         subjects affected / exposed
    1 / 154 (0.65%)
    3 / 158 (1.90%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    Arteriospasm coronary
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Intracardiac thrombus
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Right ventricular failure
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Nervous system disorders
    Cerebral infarction
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Hypoxic-ischaemic encephalopathy
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Ischaemic stroke
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Neuralgia
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 154 (0.65%)
    2 / 158 (1.27%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 154 (0.65%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Vomiting
         subjects affected / exposed
    0 / 154 (0.00%)
    2 / 158 (1.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal ulcer
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stomatitis
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic failure
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Renal failure acute
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal failure chronic
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 154 (0.65%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    6 / 154 (3.90%)
    3 / 158 (1.90%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 3
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 154 (0.00%)
    3 / 158 (1.90%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Anal abscess
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection bacterial
         subjects affected / exposed
    0 / 154 (0.00%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 154 (0.65%)
    0 / 158 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    2 / 154 (1.30%)
    1 / 158 (0.63%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Erlotinib 150 mg Erlotinib 300 mg
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    115 / 154 (74.68%)
    128 / 158 (81.01%)
    Investigations
    Weight decreased
         subjects affected / exposed
    7 / 154 (4.55%)
    15 / 158 (9.49%)
         occurrences all number
    7
    16
    Nervous system disorders
    Headache
         subjects affected / exposed
    9 / 154 (5.84%)
    2 / 158 (1.27%)
         occurrences all number
    9
    2
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    21 / 154 (13.64%)
    26 / 158 (16.46%)
         occurrences all number
    28
    30
    Chest pain
         subjects affected / exposed
    7 / 154 (4.55%)
    14 / 158 (8.86%)
         occurrences all number
    7
    18
    Asthenia
         subjects affected / exposed
    9 / 154 (5.84%)
    12 / 158 (7.59%)
         occurrences all number
    10
    14
    Pain
         subjects affected / exposed
    8 / 154 (5.19%)
    5 / 158 (3.16%)
         occurrences all number
    8
    5
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    6 / 154 (3.90%)
    8 / 158 (5.06%)
         occurrences all number
    6
    8
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    29 / 154 (18.83%)
    46 / 158 (29.11%)
         occurrences all number
    36
    56
    Nausea
         subjects affected / exposed
    20 / 154 (12.99%)
    17 / 158 (10.76%)
         occurrences all number
    21
    19
    Vomiting
         subjects affected / exposed
    13 / 154 (8.44%)
    14 / 158 (8.86%)
         occurrences all number
    14
    15
    Constipation
         subjects affected / exposed
    9 / 154 (5.84%)
    11 / 158 (6.96%)
         occurrences all number
    9
    11
    Dyspepsia
         subjects affected / exposed
    3 / 154 (1.95%)
    8 / 158 (5.06%)
         occurrences all number
    5
    8
    Abdominal pain upper
         subjects affected / exposed
    1 / 154 (0.65%)
    8 / 158 (5.06%)
         occurrences all number
    1
    8
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    26 / 154 (16.88%)
    19 / 158 (12.03%)
         occurrences all number
    29
    19
    Cough
         subjects affected / exposed
    23 / 154 (14.94%)
    19 / 158 (12.03%)
         occurrences all number
    25
    25
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    43 / 154 (27.92%)
    75 / 158 (47.47%)
         occurrences all number
    53
    101
    Dry skin
         subjects affected / exposed
    13 / 154 (8.44%)
    17 / 158 (10.76%)
         occurrences all number
    14
    19
    Pruritus
         subjects affected / exposed
    8 / 154 (5.19%)
    16 / 158 (10.13%)
         occurrences all number
    9
    17
    Dermatitis acneiform
         subjects affected / exposed
    11 / 154 (7.14%)
    9 / 158 (5.70%)
         occurrences all number
    11
    9
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    8 / 154 (5.19%)
    6 / 158 (3.80%)
         occurrences all number
    11
    6
    Pain in extremity
         subjects affected / exposed
    3 / 154 (1.95%)
    8 / 158 (5.06%)
         occurrences all number
    3
    8
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    26 / 154 (16.88%)
    32 / 158 (20.25%)
         occurrences all number
    28
    33

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 May 2011
    •Clarified exclusion criteria to allow the prior use of bevacizumab as standard first-line treatment for Non-small cell lung cancer (NSCLC). •Clarified exclusion criteria to exclude patients with previously diagnosed and treated brain metastases with symptomatic evidence. •Allowed screening evaluations to be performed on the same day as the patient’s inclusion provided all the results were obtained prior to inclusion and visit descriptions were aligned for consistency with the laboratory manual, Interactive web response system (IWRS) Electronic case report form (eCRF). •Allowed the results of screening laboratory assessments done within 3 days prior to inclusion to be used for the Baseline laboratory assessment.
    09 Jul 2013
    •The primary endpoint of Progression-free survival (PFS), as well as response, was updated to be solely based on the investigator-assessed response evaluation; an independent review committee was no longer used due to accumulating evidence pointing to limited value of independent reviews in double-blind, randomized clinical studies. •The protocol originally specified a randomized stratification by geographical region (Eastern Europe, Western Europe and Asia). However during the study only two strata were used (Europe and Asia) for randomization. •The original recruitment period was estimated to be approximately 18 months. Due to slower than expected recruitment, the recruitment period was changed so that it would be closed when approximately 300 patients had been randomized into the study. •This study was event-driven. The primary analysis was scheduled to be undertaken once approximately 277 PFS events (corresponding to the needed number of PFS events for the primary analysis) had occurred. Data were collected and queries answered until database lock, following the receipt of the 277th PFS event. Originally it was thought that this required number of events would be achieved approximately 6 months after the last patient was recruited; however as timing could not be predicted, this reference to the 6-month time frame was removed. Study treatment continued until disease progression, death, unacceptable toxicity or clinician/patient decision to stop study treatment. It was deemed to be likely that some patients would still be on study drug at the end of the study (upon database lock). Patients still receiving treatment were unblinded and patients who were receiving the experimental dose of erlotinib at the end of the study continued to be provided with erlotinib on an ongoing basis through clinical study supply, until disease progression, death, unacceptable toxicity or clinician/patient decision to stop this therapy.

    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-Thu Apr 25 22:11:29 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA