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   43874   clinical trials with a EudraCT protocol, of which   7293   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 Randomized, Multicentre, Open-Label, Phase III Study of Lapatinib plus Capecitabine versus Trastuzumab plus Capecitabine in Subjects with Anthracycline- or Taxane-Exposed ErbB2-Positive Metastatic Breast Cancer Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.nov for complete trial results.

    Summary
    EudraCT number
    		 2008-000673-38
    Trial protocol
    		 DE   FR   ES   BE   IT   SE   DK   HU   GB   GR  
    Global end of trial date
    22 Mar 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Apr 2019
    First version publication date
    07 Apr 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    EGF111438
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00820222
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, novartis.email@novartis.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
    22 Mar 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    22 Mar 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective was to evaluate the effect of lapatinib plus capecitabine on incidence of central nervous system (CNS) metastases as site of first relapse as compared with trastuzumab plus capecitabine.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Apr 2009
    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
    Belgium: 4
    Country: Number of subjects enrolled
    Denmark: 3
    Country: Number of subjects enrolled
    France: 30
    Country: Number of subjects enrolled
    Germany: 32
    Country: Number of subjects enrolled
    Greece: 7
    Country: Number of subjects enrolled
    Hungary: 20
    Country: Number of subjects enrolled
    Italy: 47
    Country: Number of subjects enrolled
    Poland: 86
    Country: Number of subjects enrolled
    Russian Federation: 197
    Country: Number of subjects enrolled
    Spain: 31
    Country: Number of subjects enrolled
    Sweden: 8
    Country: Number of subjects enrolled
    Thailand: 8
    Country: Number of subjects enrolled
    United Kingdom: 64
    Country: Number of subjects enrolled
    United States: 3
    Worldwide total number of subjects
    540
    EEA total number of subjects
    332
    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)
    447
    From 65 to 84 years
    93
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The study was terminated based on the IDMC recommendation in 2012 and collection of efficacy data was discontinued.

    Pre-assignment
    Screening details
    		 An amended protocol allowed subjects to enroll in a Long Term Follow Up if they had evidence of clinical benefit but no local access to standard of care treatments. Subjects received study treatment until until disease progression, unacceptable toxicity, or participant withdrawal.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Lapatinib plus Capecitabine
    Arm description
    		 Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lapatinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Lapatinib 1250 mg once daily

    Investigational medicinal product name
    Capecitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Capecitabine 2000mg/m2/day, days 1-14, every 21 days

    Arm title
    		 Trastuzumab plus Capecitabine
    Arm description
    		 Participants received an intravenous (IV) infusion of trastuzumab 8 mg/kilogram (kg) on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Trastuzumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Trastuzumab loading dose of 8mg/kg followed by 6mg/kg q3weekly infusions.

    Investigational medicinal product name
    Capecitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Capecitabine 2500mg/m2/day, days 1-14, every 21 days

    Number of subjects in period 1
    		Lapatinib plus Capecitabine Trastuzumab plus Capecitabine
    Started
    271
    269
    Completed
    95
    79
    Not completed
    176
    190
         Consent withdrawn by subject
    19
    21
         Physician decision
    93
    88
         Sponsor Terminated Study
    43
    65
         Lost to follow-up
    10
    9
         Unkown
    11
    7

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Lapatinib plus Capecitabine
    Reporting group description
    		 Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

    Reporting group title
    Trastuzumab plus Capecitabine
    Reporting group description
    		 Participants received an intravenous (IV) infusion of trastuzumab 8 mg/kilogram (kg) on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

    Reporting group values
    		 Lapatinib plus Capecitabine Trastuzumab plus Capecitabine Total
    Number of subjects
    		 271 269 540
    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)
    		 237 210 447
        From 65-84 years
    		 34 59 93
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 53.4 ( 10.23 ) 55.8 ( 10.26 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 271 269 540
        Male
    		 0 0 0
    Race/Ethnicity, Customized
    Units: Subjects
        White - White/Caucasian/European
    		 266 260 526
        White - Arabic/North African Heritage
    		 0 1 1
        African American/African Heritage
    		 1 1 2
        Asian - Central/South Asian Heritage
    		 1 1 2
        Asian - East Asian Heritage
    		 1 2 3
        Asian - South East Asian Heritage
    		 2 3 5
        Native Hawaiian or other Pacific Islander
    		 0 1 1

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Lapatinib plus Capecitabine
    Reporting group description
    		 Participants received a daily dose of 5 tablets of lapatinib (1250 milligrams [mg]) at approximately the same time every day, either 1 hour (or more) before breakfast or 1 hour (or more) after breakfast. Participants also received capecitabine 2000 mg per meters squared (mg/m^2) per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

    Reporting group title
    Trastuzumab plus Capecitabine
    Reporting group description
    		 Participants received an intravenous (IV) infusion of trastuzumab 8 mg/kilogram (kg) on Day 1, followed by a 6 mg/kg infusion every 3 weeks. Participants also received capecitabine 2500 mg/m^2 per day (divided and administered orally twice daily, 12 hours apart), for 14 days, every 21 days. Capecitabine was taken with food or within 30 minutes after food. Participants received study medication until disease progression, unacceptable toxicity, or participant withdrawal.

    Primary: Number of participants with Central Nervous System (CNS) metastases (as assessed by independent review) as the site of first relapse

    		 Close Top of page
    End point title
    		 Number of participants with Central Nervous System (CNS) metastases (as assessed by independent review) as the site of first relapse
    End point description
    CNS relapse is defined as the appearance of >=1 enhancing lesion measuring >=6 millimeters (mm) on T1Weighted (T1W) Magnetic Resonance Imaging (MRI) without CNS symptoms that were considered to be unequivocal based on all relevant radiological features (e.g., associated T2W signal abnormality); the appearance of any enhancing lesion on T1W MRI with CNS symptoms; unequivocal finding of leptomeningeal disease (defined as the dissemination of cancer throughout the spinal fluid), with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without symptoms. In the event of the appearance of a <6 mm lesions(s) without CNS lesions, or equivocal findings potentially suggesting leptomeningeal disease, these findings were followed with a subsequent scan within 6 weeks. If unequivocal progression was determined with the subsequent scan and/or CNS symptoms occurred, then CNS relapse crieria were met.
    End point type
    Primary
    End point timeframe
    From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012
    End point values
    		 Lapatinib plus Capecitabine Trastuzumab plus Capecitabine
    Number of subjects analysed
    251
    250
    Units: participants
    8
    12
    Statistical analysis title
    		 Comparison of CNS metastases
    Comparison groups
    Lapatinib plus Capecitabine v Trastuzumab plus Capecitabine
    Number of subjects included in analysis
    501
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.36
    Method
    		 Odds Ratio
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.26
         upper limit
    		 1.63

    Secondary: Progression free survival (PFS), as assessed by the investigator

    		 Close Top of page
    End point title
    		 Progression free survival (PFS), as assessed by the investigator
    End point description
    PFS is defined as the interval between the date of randomization and the earliest date of progressive disease (PD), or death due to any cause. PD is defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions based on investigator assessment of both CNS and non-CNS for response.
    End point type
    Secondary
    End point timeframe
    From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012
    End point values
    		 Lapatinib plus Capecitabine Trastuzumab plus Capecitabine
    Number of subjects analysed
    271
    269
    Units: months
        median (confidence interval 95%)
    6.60 (5.72 to 8.11)
    8.05 (6.14 to 8.90)
    Statistical analysis title
    		 Hazard Ratio for Progression Free Survival
    Comparison groups
    Lapatinib plus Capecitabine v Trastuzumab plus Capecitabine
    Number of subjects included in analysis
    540
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.021
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.04
         upper limit
    		 1.64
    Notes
    [1] - A HR > 1 indicates a higher risk for lapatinib+capecitabine compared with trastuzumab+capecitabine.

    Secondary: Time to first CNS progression, defined as the time from randomization until the date of documented CNS progression as the first site of relapse

    		 Close Top of page
    End point title
    		 Time to first CNS progression, defined as the time from randomization until the date of documented CNS progression as the first site of relapse
    End point description
    CNS relapse is defined as the appearance of >=1 enhancing lesion measuring >=6 mm on T1W MRI without CNS symptoms that were considered to be unequivocal based on all relevant radiological features (e.g., associated T2W signal abnormality); the appearance of any enhancing lesion on T1W MRI with CNS symptoms; unequivocal finding of leptomeningeal disease (defined as the dissemination of cancer throughout the spinal fluid), with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without symptoms. In the event of the appearance of a <6 mm lesions(s) without CNS lesions, or equivocal findings potentially suggesting leptomeningeal disease, these findings were followed with a subsequent scan within 6 weeks. If unequivocal progression was determined with the subsequent scan and/or CNS symptoms occurred, then CNS relapse crieria were met.
    End point type
    Secondary
    End point timeframe
    From randomization until the date of documented CNS progression (average of 10 months). Cut-off 11-Jun-2012
    End point values
    		 Lapatinib plus Capecitabine Trastuzumab plus Capecitabine
    Number of subjects analysed
    8
    12
    Units: months
        arithmetic mean (standard deviation)
    8.2 ( 6.78 )
    6.7 ( 6.94 )
    No statistical analyses for this end point

    Secondary: Overall survival

    		 Close Top of page
    End point title
    		 Overall survival
    End point description
    Overall survival is defined as the time from randomization until death due to any cause or to the date of censor. In the absence of confirmation of death, survival time was to be censored at the time of the last investigator contact.
    End point type
    Secondary
    End point timeframe
    From randomization until death due to any cause (average of 10 months). Cut-off 11-Jun-2012
    End point values
    		 Lapatinib plus Capecitabine Trastuzumab plus Capecitabine
    Number of subjects analysed
    271
    269
    Units: months
        median (confidence interval 95%)
    22.7 (19.5 to 999)
    27.3 (23.7 to 999)
    Statistical analysis title
    		 Hazard Ratio for Overall Survival
    Comparison groups
    Lapatinib plus Capecitabine v Trastuzumab plus Capecitabine
    Number of subjects included in analysis
    540
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [2]
    P-value
    		 = 0.095
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.9
    Notes
    [2] - A HR > 1 indicates a higher risk for lapatinib+capecitabine compared with trastuzumab+capecitabine.

    Secondary: Number of participants with Overall Response (OR), as assessed by the investigator

    		 Close Top of page
    End point title
    		 Number of participants with Overall Response (OR), as assessed by the investigator
    End point description
    OR is defined as the number of participants with either a confirmed complete response (CR; disappearance of all target lesions) or partial response (PR: at least a 30% decrease in the sum of the LD of the target lesions, compared with the baseline sum LD). CR and PR were assessed per Response Evaluation Criteria in Solid Tumors (RECIST). To be assigned a status of PR or CR, a confirmatory disease assessment was to be performed 28 days (4 weeks) or greater after the criteria for response were first met. In addition, a bone scan must have been obtained to rule out the presence of new bone lesions or progression of existing bone lesions, even if the participant had no bone lesions present at Baseline. If a bone scan was performed at the time of initial response or near the time of response, the bone scan did not need to be repeated.
    End point type
    Secondary
    End point timeframe
    From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012
    End point values
    		 Lapatinib plus Capecitabine Trastuzumab plus Capecitabine
    Number of subjects analysed
    271
    269
    Units: participants
        CR
    8
    12
        PR
    65
    73
        Overall Response (CR + PR)
    73
    85
    Statistical analysis title
    		 Odds Ratio for Overall Response
    Comparison groups
    Lapatinib plus Capecitabine v Trastuzumab plus Capecitabine
    Number of subjects included in analysis
    540
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2731
    Method
    		 Fisher exact
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.7984
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5407
         upper limit
    		 1.1771

    Secondary: Number of participants with clinical benefit (CB)

    		 Close Top of page
    End point title
    		 Number of participants with clinical benefit (CB)
    End point description
    CB is defined as the number of participants with evidence of confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of the target lesions, compared with the baseline sum LD) at any time or stable disease (SD, neither sufficient shrinkage to qualify for a PR nor sufficient increase to qualify for PD [defined as at least a 20% increase in the sum of the LD of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions] based on investigator assessment), for at least 24 weeks.
    End point type
    Secondary
    End point timeframe
    From randomization until disease progression, death, or discontinuation from the study (average of 10 months). Cut-off 11-Jun-2012
    End point values
    		 Lapatinib plus Capecitabine Trastuzumab plus Capecitabine
    Number of subjects analysed
    271
    269
    Units: participants
        CR
    8
    12
        PR
    65
    73
        SD >= 24 weeks
    39
    33
        Clinical Benefit (CR + PR + SD >= 24 weeks)
    112
    118
    Statistical analysis title
    		 Odds Ratio for Clinical Benefit
    Comparison groups
    Lapatinib plus Capecitabine v Trastuzumab plus Capecitabine
    Number of subjects included in analysis
    540
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.6106
    Method
    		 Fisher exact
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    0.9016
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6315
         upper limit
    		 1.2866

    Secondary: Duration of response

    		 Close Top of page
    End point title
    		 Duration of response
    End point description
    Duration of response is defined as the time from the first documented evidence of CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of the LD of the target lesions, compared with the baseline sum LD) until the first documented sign of PD (at least a 20% increase in the sum of the LD of target lesions, compared with the smallest sum LD recorded since the treatment started, or the appearance of 1 or more new lesions) or death due to breast cancer. In the absence of confirmation of death, survival time was to be censored at the time of the last investigator contact.
    End point type
    Secondary
    End point timeframe
    From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (average of 10 months). Cut-off 11-Jun-2012
    End point values
    		 Lapatinib plus Capecitabine Trastuzumab plus Capecitabine
    Number of subjects analysed
    73
    85
    Units: months
        median (confidence interval 95%)
    6.2 (5.3 to 10.6)
    8.4 (6.0 to 21.6)
    No statistical analyses for this end point

    Secondary: Number of participants with CNS progression at any time

    		 Close Top of page
    End point title
    		 Number of participants with CNS progression at any time
    End point description
    CNS progression was documented by a brain scan and was indicated by the investigator on the follow-up electronic Case Report Form. CNS relapse is defined as the appearance of >=1 enhancing lesion measuring >=6 mm on T1W MRI without CNS symptoms that were considered to be unequivocal based on all relevant radiological features (e.g., associated T2W signal abnormality); the appearance of any enhancing lesion on T1W MRI with CNS symptoms; unequivocal finding of leptomeningeal disease, with or without symptoms; and unequivocal finding of multifocal intraparenchymal lesions with or without symptoms. In the event of the appearance of a <6 mm lesions(s) without CNS lesions, or equivocal findings potentially suggesting leptomeningeal disease, these findings were followed with a subsequent scan within 6 weeks. If unequivocal progression was determined with the subsequent scan and/or CNS symptoms occurred, then CNS relapse crieria were met.
    End point type
    Secondary
    End point timeframe
    From the time of randomization until death due to any cause (average of 10 months). Cut-off 11-Jun-2012
    End point values
    		 Lapatinib plus Capecitabine Trastuzumab plus Capecitabine
    Number of subjects analysed
    251
    250
    Units: participants
    17
    15
    No statistical analyses for this end point

    Secondary: Number of participants with qualitative and quantitative toxicities

    		 Close Top of page
    End point title
    		 Number of participants with qualitative and quantitative toxicities
    End point description
    Qualitative and quantitative toxicities were measured as AEs. See the outcome measure entitled "Number of participants with the indicated Grade 3 or Grade 4 Adverse Events (AEs) occurring in >=2 participants in either treatment arm" and the AE module of this results summary for a list of AEs occurring in the study. An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
    End point type
    Secondary
    End point timeframe
    From the first dose of study medication until 30 days after the last dose of study treatment (average of 10 months)
    End point values
    		 Lapatinib plus Capecitabine Trastuzumab plus Capecitabine
    Number of subjects analysed
    0 [3]
    0 [4]
    Units: participants
    Notes
    [3] - Reported in the AE module of this results summary.
    [4] - Reported in the AE module of this results summary.
    No statistical analyses for this end point

    Secondary: Number of participants expressing glucocorticoid receptor, phosphatase and tensin homolog (PTEN), phosphatidylinositide 3-kinase (PI3K)/AKT, protein 53 (P53), insulin-like growth factor-1 (IGF-1), and genes involved in cell cycle regulation

    		 Close Top of page
    End point title
    		 Number of participants expressing glucocorticoid receptor, phosphatase and tensin homolog (PTEN), phosphatidylinositide 3-kinase (PI3K)/AKT, protein 53 (P53), insulin-like growth factor-1 (IGF-1), and genes involved in cell cycle regulation
    End point description
    Because the study terminated early, pharmacogenetic and biomarker analyses were not performed.
    End point type
    Secondary
    End point timeframe
    Baseline
    End point values
    		 Lapatinib plus Capecitabine Trastuzumab plus Capecitabine
    Number of subjects analysed
    0 [5]
    0 [6]
    Units: participants
    Notes
    [5] - Because the study terminated early, pharmacogenetic and biomarker analyses were not performed.
    [6] - Because the study terminated early, pharmacogenetic and biomarker analyses were not performed.
    No statistical analyses for this end point

    Secondary: Number of participants with the indicated Grade 3 or Grade 4 Adverse Events (AEs) occurring in >=2% of participants in either treatment arm

    		 Close Top of page
    End point title
    		 Number of participants with the indicated Grade 3 or Grade 4 Adverse Events (AEs) occurring in >=2% of participants in either treatment arm
    End point description
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The Investigator assessed whether the AE was related to study drug. AEs were graded using the Common Toxicity Criteria from the Cancer Therapy Evaluation Program, Division of Cancer Therapy, National Cancer Institute. Grades: 0=No AE or within normal limits; 1=Mild AE; 2=Moderate AE; 3=Severe and undesirable AE; 4=Life-threatening or disabling AE; 5=Death related to AE.
    End point type
    Secondary
    End point timeframe
    From the first dose of study medication until 30 days after the last dose of study treatment (average of 10 months).
    End point values
    		 Lapatinib plus Capecitabine Trastuzumab plus Capecitabine
    Number of subjects analysed
    270
    267
    Units: participants
        Palmar-plantar erythrodysaesthesia syndrome
    29
    45
        Diarrhoea
    19
    22
        Aspartate aminotransferase increased
    11
    4
        Neutropenia
    9
    18
        Asthenia
    9
    6
        Fatigue
    7
    4
        Alanine aminotransferase increased
    4
    6
        Hypokalaemia
    3
    11
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From randomization until up to and including 30 days after the last dose of study treatment (up to 7 years post randomization)
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Lapatinib + Capecitabine
    Reporting group description
    		 Lapatinib + Capecitabine

    Reporting group title
    Trastuzumab + Capecitabine
    Reporting group description
    		 Trastuzumab + Capecitabine

    Serious adverse events
    		 Lapatinib + Capecitabine Trastuzumab + Capecitabine
    Total subjects affected by serious adverse events
         subjects affected / exposed
    41 / 270 (15.19%)
    51 / 267 (19.10%)
         number of deaths (all causes)
    12
    3
         number of deaths resulting from adverse events
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour haemorrhage
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 270 (0.37%)
    2 / 267 (0.75%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pelvic venous thrombosis
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    1 / 270 (0.37%)
    2 / 267 (0.75%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombosis
         subjects affected / exposed
    0 / 270 (0.00%)
    2 / 267 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vena cava thrombosis
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 270 (0.37%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucosal inflammation
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 270 (0.00%)
    2 / 267 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    3 / 270 (1.11%)
    3 / 267 (1.12%)
         occurrences causally related to treatment / all
    4 / 6
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Cervical dysplasia
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Aspiration
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    2 / 270 (0.74%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleurisy
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Productive cough
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    3 / 270 (1.11%)
    6 / 267 (2.25%)
         occurrences causally related to treatment / all
    1 / 3
    3 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 270 (0.74%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 270 (0.37%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ejection fraction decreased
         subjects affected / exposed
    0 / 270 (0.00%)
    3 / 267 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    4 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Platelet count decreased
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Left ventricular dysfunction
         subjects affected / exposed
    0 / 270 (0.00%)
    2 / 267 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral haematoma
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Cerebrovascular accident
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Haemorrhagic stroke
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Headache
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hemiplegia
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic stroke
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurological decompensation
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 270 (0.37%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    2 / 270 (0.74%)
    6 / 267 (2.25%)
         occurrences causally related to treatment / all
    2 / 2
    5 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 270 (0.37%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain upper
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    2 / 270 (0.74%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    4 / 270 (1.48%)
    10 / 267 (3.75%)
         occurrences causally related to treatment / all
    5 / 6
    10 / 10
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal inflammation
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 270 (0.37%)
    2 / 267 (0.75%)
         occurrences causally related to treatment / all
    1 / 1
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 270 (0.74%)
    2 / 267 (0.75%)
         occurrences causally related to treatment / all
    2 / 3
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stevens-Johnson syndrome
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 270 (0.37%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Erysipelas
         subjects affected / exposed
    1 / 270 (0.37%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 270 (0.37%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis bacterial
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Localised infection
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    2 / 270 (0.74%)
    2 / 267 (0.75%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyelonephritis acute
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 270 (0.37%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 270 (0.00%)
    2 / 267 (0.75%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 270 (0.37%)
    2 / 267 (0.75%)
         occurrences causally related to treatment / all
    0 / 4
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral pharyngitis
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperuricaemia
         subjects affected / exposed
    2 / 270 (0.74%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    1 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 270 (0.00%)
    3 / 267 (1.12%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 270 (0.00%)
    1 / 267 (0.37%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 270 (0.37%)
    0 / 267 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Lapatinib + Capecitabine Trastuzumab + Capecitabine
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    241 / 270 (89.26%)
    236 / 267 (88.39%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    34 / 270 (12.59%)
    35 / 267 (13.11%)
         occurrences all number
    45
    43
    Aspartate aminotransferase increased
         subjects affected / exposed
    33 / 270 (12.22%)
    30 / 267 (11.24%)
         occurrences all number
    42
    39
    Blood alkaline phosphatase increased
         subjects affected / exposed
    17 / 270 (6.30%)
    11 / 267 (4.12%)
         occurrences all number
    18
    15
    Blood bilirubin increased
         subjects affected / exposed
    19 / 270 (7.04%)
    9 / 267 (3.37%)
         occurrences all number
    48
    15
    Nervous system disorders
    Headache
         subjects affected / exposed
    15 / 270 (5.56%)
    17 / 267 (6.37%)
         occurrences all number
    26
    17
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    22 / 270 (8.15%)
    27 / 267 (10.11%)
         occurrences all number
    31
    38
    Leukopenia
         subjects affected / exposed
    11 / 270 (4.07%)
    21 / 267 (7.87%)
         occurrences all number
    19
    43
    Neutropenia
         subjects affected / exposed
    38 / 270 (14.07%)
    44 / 267 (16.48%)
         occurrences all number
    77
    91
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    46 / 270 (17.04%)
    45 / 267 (16.85%)
         occurrences all number
    80
    63
    Fatigue
         subjects affected / exposed
    26 / 270 (9.63%)
    33 / 267 (12.36%)
         occurrences all number
    47
    41
    Mucosal inflammation
         subjects affected / exposed
    21 / 270 (7.78%)
    27 / 267 (10.11%)
         occurrences all number
    31
    42
    Pyrexia
         subjects affected / exposed
    19 / 270 (7.04%)
    25 / 267 (9.36%)
         occurrences all number
    28
    34
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    21 / 270 (7.78%)
    16 / 267 (5.99%)
         occurrences all number
    27
    20
    Diarrhoea
         subjects affected / exposed
    125 / 270 (46.30%)
    107 / 267 (40.07%)
         occurrences all number
    300
    209
    Dyspepsia
         subjects affected / exposed
    21 / 270 (7.78%)
    19 / 267 (7.12%)
         occurrences all number
    24
    20
    Nausea
         subjects affected / exposed
    82 / 270 (30.37%)
    50 / 267 (18.73%)
         occurrences all number
    116
    79
    Stomatitis
         subjects affected / exposed
    16 / 270 (5.93%)
    23 / 267 (8.61%)
         occurrences all number
    22
    27
    Vomiting
         subjects affected / exposed
    35 / 270 (12.96%)
    27 / 267 (10.11%)
         occurrences all number
    60
    35
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    35 / 270 (12.96%)
    26 / 267 (9.74%)
         occurrences all number
    67
    50
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    22 / 270 (8.15%)
    16 / 267 (5.99%)
         occurrences all number
    25
    16
    Dyspnoea
         subjects affected / exposed
    11 / 270 (4.07%)
    18 / 267 (6.74%)
         occurrences all number
    12
    18
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    15 / 270 (5.56%)
    7 / 267 (2.62%)
         occurrences all number
    18
    7
    Nail disorder
         subjects affected / exposed
    21 / 270 (7.78%)
    13 / 267 (4.87%)
         occurrences all number
    21
    14
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    142 / 270 (52.59%)
    160 / 267 (59.93%)
         occurrences all number
    238
    222
    Rash
         subjects affected / exposed
    66 / 270 (24.44%)
    21 / 267 (7.87%)
         occurrences all number
    90
    26
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    16 / 270 (5.93%)
    13 / 267 (4.87%)
         occurrences all number
    22
    14
    Pain in extremity
         subjects affected / exposed
    14 / 270 (5.19%)
    9 / 267 (3.37%)
         occurrences all number
    15
    15
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    28 / 270 (10.37%)
    21 / 267 (7.87%)
         occurrences all number
    33
    21

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    16 Mar 2009
    Country specific amendment was done for Sweden to modify exclusion criteria and allow subjects participating in Study LAP112867 who had short exposure to lapatinib to be eligible for this study.
    08 Sep 2010
    Changed description of the primary endpoint of the study and mandated independent review of baseline brain MRI scan for eligibility purpose and changes in analysis plan. Other amendments were made on inclusion/exclusion criteria and some study procedures and biomarker research.
    30 Nov 2011
    Minimum of one primary analysis utilizing an IDMC review to assess safety, PFS events and futility analysis on primary endpoint.
    10 Sep 2012
    The study was terminated based on the IDMC recommendation. However, this amendment allowed subjects to receive either lapatinib in combination with capecitabine or trastuzumab in combination with capecitabine where there was no local access to standard of care treatments.
    24 Mar 2016
    Deleted or replaced references to GSK or its staff with that of Novartis/Novartis and its authorized agents. Made administrative changes to align with Novartis processes and procedures.

    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.
    Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.nov for complete trial results.
    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-Wed May 08 14:18:38 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA