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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   38485   clinical trials with a EudraCT protocol, of which   6324   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).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A study of lapatinib in combination with oxaliplatin and capecitabine in early HER-2 overexpressing oesophageal and gastric cancers.

    Summary
    EudraCT number
    2010-019602-16
    Trial protocol
    GB  
    Global end of trial date
    26 Mar 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    08 Jul 2016
    First version publication date
    30 Jul 2015
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    N/A
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Cambridge University Hospitals NHS Foundation Trust
    Sponsor organisation address
    Hills Road, Cambridge University Hospitals NHS Foundation Trus, United Kingdom, CB2 0QQ
    Public contact
    Prasanna Kapilan, Cambridge clinical trials unit (CCTU) , +44 1223 216524, Prasanna.kapilan@addenbrookes.nhs.uk
    Scientific contact
    Hugo Ford, Cambridge University Hospitals NHS Foundation Trust , +44 1223 216524, hugo.ford@addenbrookes.nhs.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Oct 2014
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Sep 2014
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Mar 2015
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    "Assess ability of ex vivo molecular response to predict molecular response on a biopsy after 10 days of treatment with lapatinib, and to report observations of patterns of radiological, functional imaging and pathological response associated with molecular response"
    Protection of trial subjects
    "Additional visits for investigations no risks. Where possible tests will be scheduled on the same day to minimise inconvenience. Additional endoscopy: Minimal risk. Where possible pretreatment research biopsies will be obtained at a routine endoscopy visit rather than at an additional visit. The day 10 endoscopy is unavoidable. Radiation risk from additional PET/CT scan: There is a small additional risk of second malignancy from the PET/CT scan and from MUGA scan if required. This is unavoidable but patients will be fully informed in the information sheet Toxicity from Lapatinib: The main potential side effects from lapatinib are diarrhoea, skin rash and heart toxicity. Diarrhoea and rash are normally easily managed without great distress to the patient. Heart toxicity is rare, but to minimise the chance of it being a problem we will be monitoring heart function throughtout treatment with echocardiograms. Although these tests involve an additional hospital visit they are noninvasive and should not cause any discomfort or distress. In addition we have modified the standard chemotherapy to minimise the risk of toxicity of the combination of lapatinib with standard treatment. This involves omitting one drug (epirubicin) which is known to also damage heart tissue, and reducing the dose of capecitabine. This combination at these doses has already been tested in gastric cancer and has been found to be safe and effective, but to ensure patient safety we are performing a formal safety analysis after 6 patients have been recruited to ensure there is no need for further modifications."
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    24 May 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 10
    Worldwide total number of subjects
    10
    EEA total number of subjects
    10
    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)
    6
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    1st patient registered 05/07/2011, last patient registered 15/04/2013. Patients were recruited from two English sites in the patients' oncology clinics.

    Pre-assignment
    Screening details
    Patients underwent pre-treatment Oesophago-gastro-duodenoscopy (OGD) and biopsy.

    Pre-assignment period milestones
    Number of subjects started
    187 [1]
    Number of subjects completed
    10

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    Consent withdrawn by subject: 9
    Reason: Number of subjects
    Not meeting inclusion criteria as HER2 negative: 134
    Reason: Number of subjects
    Not meeting inclusion criteria - other reasons (20: 34
    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: 187 patients assessed for eligibility and 177 patients excluded, so 10 patients enrolled for protocol treatment.
    Period 1
    Period 1 title
    On-Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Not applicable
    Blinding used
    Not blinded

    Arms
    Arm title
    All patients
    Arm description
    All registered subjects, planned to receive lapatinib in combination with oxaliplatin & capecitabine.
    Arm type
    Experimental

    Investigational medicinal product name
    Oxaliplatin
    Investigational medicinal product code
    Other name
    Eloxatin
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    "130 mg/m2 IV in 250-500 ml of 5% glucose over 2 hours (given once every 21 days for three cycles starting on day 11 of the trial)"

    Investigational medicinal product name
    capecitabine
    Investigational medicinal product code
    Other name
    Xeloda
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    850mg/m2 b.i.d po for 14 days.

    Investigational medicinal product name
    850mg/m2 b.i.d po for 14 days
    Investigational medicinal product code
    Other name
    Tyverb
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    1250 mg od po for days 1-72

    Number of subjects in period 1
    All patients
    Started
    10
    10-day Induction period
    10
    Proceeded with surgery
    9
    Completed
    7
    Not completed
    3
         Adverse event, non-fatal
    2
         Consent withdrawn by subject
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    On-Study
    Reporting group description
    -

    Reporting group values
    On-Study Total
    Number of subjects
    10 10
    Age categorical
    All registered subjects, planned to receive lapatinib in combination with oxaliplatin & capecitabine.
    Units: Subjects
        In utero
    0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0
        Newborns (0-27 days)
    0 0
        Infants and toddlers (28 days-23 months)
    0 0
        Children (2-11 years)
    0 0
        Adolescents (12-17 years)
    0 0
        Adults (18-64 years)
    6 6
        From 65-84 years
    4 4
        85 years and over
    0 0
    Age continuous
    All registered subjects, planned to receive lapatinib in combination with oxaliplatin & capecitabine
    Units: years
        arithmetic mean (standard deviation)
    61.7 ± 9.4 -
    Gender categorical
    All registered subjects, planned to receive lapatinib in combination with oxaliplatin & capecitabine.
    Units: Subjects
        Female
    3 3
        Male
    7 7
    Disease Site
    Site of primary disease.
    Units: Subjects
        Oesophagus
    3 3
        Stomach
    1 1
        Oesophago-gastric Junction (OGJ) Type I
    1 1
        Oesophago-gastric Junction (OGJ) Type II
    3 3
        Oesophago-gastric Junction (OGJ) Type III
    2 2

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    All patients
    Reporting group description
    All registered subjects, planned to receive lapatinib in combination with oxaliplatin & capecitabine.

    Subject analysis set title
    All
    Subject analysis set type
    Full analysis
    Subject analysis set description
    All registered subjects, planned to receive lapatinib in combination with oxaliplatin & capecitabine.

    Primary: Molecular response

    Close Top of page
    End point title
    Molecular response [1]
    End point description
    Concordance between molecular response in biopsies taken pre treatment and treated with lapatinib ex vivo and molecular response in a biopsy taken after 10 days of oral lapatinib in vivo (based on P-HER-2 staining on IHC only)
    End point type
    Primary
    End point timeframe
    From pre-treatment to 10 days post-treatment with lapatinib
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: This is a single arm study. The summary of primary endpoints are provided.
    End point values
    All patients All
    Number of subjects analysed
    9
    9
    Units: subjects
    number (confidence interval 95%)
        Same Response
    0.55 (0.2449 to 0.9148)
    0.55 (0.2449 to 0.9148)
    Attachments
    LEO SAE Listing
    No statistical analyses for this end point

    Secondary: Response on FGD-PET (SUV Max)

    Close Top of page
    End point title
    Response on FGD-PET (SUV Max)
    End point description
    Perecentage of responders on FDG-PET based on reduction of >35% in Standard Uptake Variable (SUV) Maximal from central review .
    End point type
    Secondary
    End point timeframe
    Please provide the time frame: it is requied for the end point definition.
    End point values
    All
    Number of subjects analysed
    9
    Units: subjects
        Non-Responder
    9
        Responder
    0
    No statistical analyses for this end point

    Secondary: Response on FGD-PET (SUV Average)

    Close Top of page
    End point title
    Response on FGD-PET (SUV Average)
    End point description
    Perecentage of responders on FDG-PET based on reduction of >35% in Standard Uptake Variable (SUV) Average from central review.
    End point type
    Secondary
    End point timeframe
    Please provide the time frame: it is requied for the end point definition
    End point values
    All
    Number of subjects analysed
    9
    Units: subjects
        Non-Responder
    9
        Responder
    0
    No statistical analyses for this end point

    Secondary: Objective Radiological Response

    Close Top of page
    End point title
    Objective Radiological Response
    End point description
    Objective Radiological Response by RECIST crieteria - Percentage of responders.
    End point type
    Secondary
    End point timeframe
    Please provide the time frame: it is requied for the end point definition
    End point values
    All
    Number of subjects analysed
    10
    Units: Subjects
    number (confidence interval 95%)
        Responder
    0.5 (0.1871 to 0.8129)
    No statistical analyses for this end point

    Secondary: R0 Resection

    Close Top of page
    End point title
    R0 Resection
    End point description
    R0 Resection - Percentage of Responders.
    End point type
    Secondary
    End point timeframe
    Please provide the time frame: it is requied for the end point definition.
    End point values
    All
    Number of subjects analysed
    9
    Units: Sujects
    number (confidence interval 95%)
        Responder
    0.778 (0.3999 to 0.9719)
    No statistical analyses for this end point

    Secondary: Pathological Complete Response

    Close Top of page
    End point title
    Pathological Complete Response
    End point description
    Pathological Complete Response - Percentage of Responders.
    End point type
    Secondary
    End point timeframe
    Please provide the time frame: it is requied for the end point definition.
    End point values
    All
    Number of subjects analysed
    9
    Units: Subjects
    number (confidence interval 95%)
        Responder
    0.333 (0.0749 to 0.7007)
    No statistical analyses for this end point

    Secondary: Overall Survival

    Close Top of page
    End point title
    Overall Survival
    End point description
    Overall Survival (months) - calculated from date of registration to date of death from any cause; suviving patients are censored at the date last known alive.
    End point type
    Secondary
    End point timeframe
    Please provide the time frame: it is requied for the end point definition.
    End point values
    All
    Number of subjects analysed
    10
    Units: Months
    median (inter-quartile range (Q1-Q3))
        Overall Survival
    32.4573 (13.7319 to 32.4573)
    No statistical analyses for this end point

    Secondary: Progression-Free Survival

    Close Top of page
    End point title
    Progression-Free Survival
    End point description
    Progression-Free Survival (months) - calculated from date of registration to date of first progression or date of death from any cause, whichever occurs first; surviving patients without disease progression are censored at the date last known alive.
    End point type
    Secondary
    End point timeframe
    Please provide the time frame: it is requied for the end point definition
    End point values
    All
    Number of subjects analysed
    10
    Units: Months
    median (inter-quartile range (Q1-Q3))
        Progression-Free Survival
    21.2714 (12.9435 to 99999)
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    Date of patient registration onto the trial and continued until 21 days after the last study drug administration.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    NCI CTC
    Dictionary version
    3
    Frequency threshold for reporting non-serious adverse events: 0%
    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: Serious adverse events are reported in the file found in the uploaded attachment.

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Apr 2011
    Inclusion of standard statements regarding the submission of complaints from patients participating in clinical trials and clarification on compensation available to patients harmed during the trial.
    10 Nov 2011
    Addition of medication diary to help us to monitor medication compliance on the trial.
    23 Mar 2012
    change to exclusion criteria, dose modifications, additional blood test added and clarification of testing to be carried out on biopsies
    13 Sep 2012
    Update the CTA to chnages the manufacturer responsible for the certification of the finished IMP and update the marketing authorisation number for Tyverb (lapatinib).
    11 Dec 2012
    Changes to details regarding secondary objectives, dose modifications for Non‐Haematological toxicities, repeat biopsies, dose limiting toxicity, sample size and molecular testing on biopsies.

    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
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA