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   43857   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 Phase II, open label, multi-center, multi-arm study of ceritinib in patients with advanced solid tumors and hematological malignancies characterized by genetic abnormalities of anaplastic lymphoma kinase (ALK)

    Summary
    EudraCT number
    		 2015-000814-23
    Trial protocol
    		 ES   DE   CZ   FR   DK   IT  
    Global end of trial date
    20 Aug 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    02 Sep 2019
    First version publication date
    02 Sep 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CLDK378A2407
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02465528
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Eudract: 2015-000814-23
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Study Director, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com
    Scientific contact
    Study Director, 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
    20 Aug 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    20 Aug 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Aug 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Assess the antitumor activity of ceritinib as measured by disease control rate (DCR) determined by Investigators.
    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
    06 May 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 8
    Country: Number of subjects enrolled
    Czech Republic: 2
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Korea, Republic of: 4
    Country: Number of subjects enrolled
    Denmark: 1
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Thailand: 2
    Country: Number of subjects enrolled
    Israel: 1
    Worldwide total number of subjects
    22
    EEA total number of subjects
    15
    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)
    18
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A minimum of 10 and a maximum of 20 subjects were to be enrolled in each arm (tumor type)

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Anaplastic large cell lymphoma (ALCL)
    Arm description
    		 Patients with a diagnosis of ALCL histologically or cytologically confirmed to be ALK-positive
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ceritinib
    Investigational medicinal product code
    LDK378
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Ceritinib was administered orally once daily at a dose of 750 mg (5 capsules of 150 mg ceritinib) on a continuous dosing schedule. A complete treatment cycle was defined as 28 days of once daily continuous treatment with ceritinib.

    Arm title
    		 Inflammatory myofibroblastic tumor (IMT)
    Arm description
    		 Patients diagnosed with IMT with a confirmed translocation involving the ALK gene
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ceritinib
    Investigational medicinal product code
    LDK378
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Ceritinib was administered orally once daily at a dose of 750 mg (5 capsules of 150 mg ceritinib) on a continuous dosing schedule. A complete treatment cycle was defined as 28 days of once daily continuous treatment with ceritinib.

    Arm title
    		 Glioblastoma (GBM)
    Arm description
    		 Patients with GBM with a translocation involving the ALK gene
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ceritinib
    Investigational medicinal product code
    LDK378
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Ceritinib was administered orally once daily at a dose of 750 mg (5 capsules of 150 mg ceritinib) on a continuous dosing schedule. A complete treatment cycle was defined as 28 days of once daily continuous treatment with ceritinib.

    Arm title
    		 Any other ALK-positive tumor
    Arm description
    		 Patients with any other ALK-positive tumor. Patients in this arm included adenocarcinoma (n= 2), sarcoma (1) and other (2).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ceritinib
    Investigational medicinal product code
    LDK378
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Ceritinib was administered orally once daily at a dose of 750 mg (5 capsules of 150 mg ceritinib) on a continuous dosing schedule. A complete treatment cycle was defined as 28 days of once daily continuous treatment with ceritinib.

    Number of subjects in period 1
    		Anaplastic large cell lymphoma (ALCL) Inflammatory myofibroblastic tumor (IMT) Glioblastoma (GBM) Any other ALK-positive tumor
    Started
    1
    4
    12
    5
    Completed
    0
    0
    0
    0
    Not completed
    1
    4
    12
    5
         Consent withdrawn by subject
    -
    -
    2
    -
         Physician decision
    -
    -
    1
    -
         Adverse event, non-fatal
    -
    -
    -
    1
         Study terminated by sponsor
    1
    2
    -
    -
         Progressive disease
    -
    2
    9
    4

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Anaplastic large cell lymphoma (ALCL)
    Reporting group description
    		 Patients with a diagnosis of ALCL histologically or cytologically confirmed to be ALK-positive

    Reporting group title
    Inflammatory myofibroblastic tumor (IMT)
    Reporting group description
    		 Patients diagnosed with IMT with a confirmed translocation involving the ALK gene

    Reporting group title
    Glioblastoma (GBM)
    Reporting group description
    		 Patients with GBM with a translocation involving the ALK gene

    Reporting group title
    Any other ALK-positive tumor
    Reporting group description
    		 Patients with any other ALK-positive tumor. Patients in this arm included adenocarcinoma (n= 2), sarcoma (1) and other (2).

    Reporting group values
    		 Anaplastic large cell lymphoma (ALCL) Inflammatory myofibroblastic tumor (IMT) Glioblastoma (GBM) Any other ALK-positive tumor Total
    Number of subjects
    		 1 4 12 5 22
    Age, Customized
    Units: Subjects
        18 to <65
    		 1 4 10 3 18
        65 to <=75
    		 0 0 2 2 4
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 36.0 ( 999.9 ) 42.8 ( 19.41 ) 49.3 ( 15.40 ) 57.4 ( 14.64 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 1 3 6 1 11
        Male
    		 0 1 6 4 11
    Race/Ethnicity, Customized
    Units: Subjects
        Caucasian
    		 0 1 10 2 13
        Asian
    		 1 1 1 3 6
        Other
    		 0 2 1 0 3

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Anaplastic large cell lymphoma (ALCL)
    Reporting group description
    		 Patients with a diagnosis of ALCL histologically or cytologically confirmed to be ALK-positive

    Reporting group title
    Inflammatory myofibroblastic tumor (IMT)
    Reporting group description
    		 Patients diagnosed with IMT with a confirmed translocation involving the ALK gene

    Reporting group title
    Glioblastoma (GBM)
    Reporting group description
    		 Patients with GBM with a translocation involving the ALK gene

    Reporting group title
    Any other ALK-positive tumor
    Reporting group description
    		 Patients with any other ALK-positive tumor. Patients in this arm included adenocarcinoma (n= 2), sarcoma (1) and other (2).

    Primary: Disease Control Rate (DCR) based on investigator assessments for participants with at least 16 weeks of treatment

    		 Close Top of page
    End point title
    		 Disease Control Rate (DCR) based on investigator assessments for participants with at least 16 weeks of treatment [1]
    End point description
    The DCR is defined as the percentage of patients with complete response (CR), partial response (PR) or stable disease (SD) at 16 weeks from the start of ceritinib treatment. The assessment criteria are: Solid Tumors (RECIST 1.1., Response Evaluation Criteria in Solid Tumors); GBM (RECIST 1.1 and RANO, Response Evaluation in Neuro-Oncology); Hematologic tumors (Cheson).
    End point type
    Primary
    End point timeframe
    Baseline up to approximately 16 weeks
    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: No analysis was done for this endpoint
    End point values
    		 Anaplastic large cell lymphoma (ALCL) Inflammatory myofibroblastic tumor (IMT) Glioblastoma (GBM) Any other ALK-positive tumor
    Number of subjects analysed
    1 [2]
    4 [3]
    12 [4]
    5 [5]
    Units: percentage of participants
        number (confidence interval 95%)
    100.00 (2.5 to 100.0)
    75.00 (19.4 to 99.4)
    0.0 (0.0 to 26.5)
    40.0 (5.3 to 85.3)
    Notes
    [2] - n=1
    [3] - n=3
    [4] - n=0
    [5] - n=2
    No statistical analyses for this end point

    Secondary: Overall Response Rate (ORR) per investigator assessment

    		 Close Top of page
    End point title
    		 Overall Response Rate (ORR) per investigator assessment
    End point description
    ORR is defined as the percentage of patients with best overall response of complete response (CR) or partial response (PR) based on local assessment according to RECIST 1.1, RANO or Cheson hematological criteria.
    End point type
    Secondary
    End point timeframe
    Baseline, every 8 weeks until disease progression or end of treatment, whichever came first assessed up to approximately 84 weeks
    End point values
    		 Anaplastic large cell lymphoma (ALCL) Inflammatory myofibroblastic tumor (IMT) Glioblastoma (GBM) Any other ALK-positive tumor
    Number of subjects analysed
    1 [6]
    4 [7]
    12 [8]
    5 [9]
    Units: percentage of participants
        number (confidence interval 95%)
    100.0 (2.5 to 100.0)
    75.0 (19.4 to 99.4)
    0.0 (0 to 26.5)
    0.0 (0.0 to 52.2)
    Notes
    [6] - n=1
    [7] - n=3
    [8] - n=0
    [9] - n=0
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) per investigator assessment

    		 Close Top of page
    End point title
    		 Duration of Response (DOR) per investigator assessment [10]
    End point description
    DOR is defined as the time from date of first documented CR or PR to date of first documented disease progression or death due to any cause
    End point type
    Secondary
    End point timeframe
    Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No analysis was done for this endpoint
    End point values
    		 Anaplastic large cell lymphoma (ALCL) Inflammatory myofibroblastic tumor (IMT)
    Number of subjects analysed
    1 [11]
    3 [12]
    Units: weeks
        median (confidence interval 95%)
    999.9 (999.9 to 999.9)
    999.9 (3.0 to 999.9)
    Notes
    [11] - n=0
    [12] - n=1
    No statistical analyses for this end point

    Secondary: Time to Response (TTR) per investigator assessment

    		 Close Top of page
    End point title
    		 Time to Response (TTR) per investigator assessment
    End point description
    TTR is defined as the time from date of the first dose to date of first documented response (CR or PR)
    End point type
    Secondary
    End point timeframe
    Baseline, every 8 weeks until disease progression or end of treatment, whichever came first, assessed up to approximately 84 weeks
    End point values
    		 Anaplastic large cell lymphoma (ALCL) Inflammatory myofibroblastic tumor (IMT) Glioblastoma (GBM) Any other ALK-positive tumor
    Number of subjects analysed
    1 [13]
    4 [14]
    12 [15]
    5 [16]
    Units: weeks
        median (confidence interval 95%)
    7.1 (0.999 to 999.9)
    16.4 (6.3 to 999.9)
    999.9 (999.9 to 999.9)
    999.9 (999.9 to 999.9)
    Notes
    [13] - n=1
    [14] - n=3
    [15] - n=0
    [16] - n=4
    No statistical analyses for this end point

    Secondary: Progression Free Survival (PFS) per investigator assessments

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS) per investigator assessments
    End point description
    PFS is defined as the time from the date of first dose of ceritinib to the date of first documented disease progression or death from any cause
    End point type
    Secondary
    End point timeframe
    Baseline, every 8 weeks until disease progression or death from any cause, assessed for up to approximately 84 weeks
    End point values
    		 Anaplastic large cell lymphoma (ALCL) Inflammatory myofibroblastic tumor (IMT) Glioblastoma (GBM) Any other ALK-positive tumor
    Number of subjects analysed
    0 [17]
    2 [18]
    9 [19]
    5 [20]
    Units: weeks
        median (confidence interval 95%)
    ( to )
    999.9 (3.7 to 999.9)
    1.7 (1.1 to 2.7)
    1.7 (1.6 to 5.1)
    Notes
    [17] - No participants met the criteria for PFS, n=0
    [18] - n=2
    [19] - n=9
    [20] - n=5
    No statistical analyses for this end point

    Secondary: Percent of on treatment participant deaths during treatment and 30 day follow-up

    		 Close Top of page
    End point title
    		 Percent of on treatment participant deaths during treatment and 30 day follow-up
    End point description
    Deaths due to any cause during treatment and 30 day follow-up
    End point type
    Secondary
    End point timeframe
    Baseline up to approximately 84 weeks
    End point values
    		 Anaplastic large cell lymphoma (ALCL) Inflammatory myofibroblastic tumor (IMT) Glioblastoma (GBM) Any other ALK-positive tumor
    Number of subjects analysed
    0 [21]
    0 [22]
    3
    1
    Units: percent of participants
        number (not applicable)
    25.0
    20.0
    Notes
    [21] - no deaths in this arm
    [22] - no deaths in this arm
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from first dose of study treatment until end of study treatment plus 28 days post treatment, up to maximum duration of approximately 84 weeks
    Adverse event reporting additional description
    Any sign or symptom that occurs during the study treatment plus 30 days post treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    Inflammatory Myofibroblastic Tumor
    Reporting group description
    		 Inflammatory Myofibroblastic Tumor

    Reporting group title
    Anaplastic Large Cell Lymphoma
    Reporting group description
    		 Anaplastic Large Cell Lymphoma

    Reporting group title
    Any other ALK+ tumor
    Reporting group description
    		 Any other ALK+ tumor

    Reporting group title
    All Subjects
    Reporting group description
    		 All Subjects

    Reporting group title
    Glioblastoma
    Reporting group description
    		 Glioblastoma

    Serious adverse events
    		 Inflammatory Myofibroblastic Tumor Anaplastic Large Cell Lymphoma Any other ALK+ tumor All Subjects Glioblastoma
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 1 (0.00%)
    4 / 5 (80.00%)
    16 / 22 (72.73%)
    10 / 12 (83.33%)
         number of deaths (all causes)
    0
    0
    1
    4
    3
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Investigations
    Haemoglobin decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Head injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Embolism
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
    2 / 12 (16.67%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    Hypersomnia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intracranial pressure increased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    2 / 5 (40.00%)
    2 / 22 (9.09%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    2 / 5 (40.00%)
    4 / 22 (18.18%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Stomatitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis allergic
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dermatitis bullous
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraneoplastic pemphigus
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrotic syndrome
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tooth infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    2 / 22 (9.09%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Inflammatory Myofibroblastic Tumor Anaplastic Large Cell Lymphoma Any other ALK+ tumor All Subjects Glioblastoma
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    4 / 4 (100.00%)
    1 / 1 (100.00%)
    5 / 5 (100.00%)
    22 / 22 (100.00%)
    12 / 12 (100.00%)
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    4 / 5 (80.00%)
    5 / 22 (22.73%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    4
    5
    1
    Fatigue
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    6 / 22 (27.27%)
    5 / 12 (41.67%)
         occurrences all number
    1
    0
    0
    6
    5
    Gait disturbance
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Oedema
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    3 / 22 (13.64%)
    3 / 12 (25.00%)
         occurrences all number
    0
    0
    0
    3
    3
    Pain
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Epistaxis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Lung disorder
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Respiratory disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    2 / 22 (9.09%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    2
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 1 (100.00%)
    1 / 5 (20.00%)
    7 / 22 (31.82%)
    2 / 12 (16.67%)
         occurrences all number
    4
    1
    1
    8
    2
    Amylase increased
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    4
    0
    0
    4
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 1 (100.00%)
    1 / 5 (20.00%)
    5 / 22 (22.73%)
    0 / 12 (0.00%)
         occurrences all number
    5
    2
    4
    11
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 1 (100.00%)
    1 / 5 (20.00%)
    4 / 22 (18.18%)
    0 / 12 (0.00%)
         occurrences all number
    3
    1
    1
    5
    0
    Blood bilirubin abnormal
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    2
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    2
    0
    Blood creatinine increased
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    0
    3
    0
    Creatinine renal clearance increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 1 (100.00%)
    1 / 5 (20.00%)
    4 / 22 (18.18%)
    0 / 12 (0.00%)
         occurrences all number
    2
    1
    1
    4
    0
    Lipase increased
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    2 / 22 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    2
    0
    Weight decreased
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    2 / 22 (9.09%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    2
    1
    Injury, poisoning and procedural complications
    Cartilage injury
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Sinus bradycardia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Tachycardia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Nervous system disorders
    Aphasia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    0
    2
    2
    Cognitive disorder
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Depressed level of consciousness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Dizziness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    2
    2
    Headache
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    3 / 22 (13.64%)
    3 / 12 (25.00%)
         occurrences all number
    0
    0
    0
    3
    3
    Hemiparesis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Somnolence
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    0
    2
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 1 (0.00%)
    3 / 5 (60.00%)
    5 / 22 (22.73%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    3
    6
    0
    Leukocytosis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    2
    0
    Lymphopenia
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    3 / 22 (13.64%)
    1 / 12 (8.33%)
         occurrences all number
    2
    0
    0
    3
    1
    Neutropenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    0
    2
    2
    Thrombocytopenia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    2 / 5 (40.00%)
    5 / 22 (22.73%)
    3 / 12 (25.00%)
         occurrences all number
    0
    0
    2
    5
    3
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 1 (100.00%)
    2 / 5 (40.00%)
    5 / 22 (22.73%)
    0 / 12 (0.00%)
         occurrences all number
    2
    1
    2
    5
    0
    Abdominal pain upper
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Constipation
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    4 / 22 (18.18%)
    2 / 12 (16.67%)
         occurrences all number
    2
    0
    0
    4
    2
    Diarrhoea
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 1 (100.00%)
    2 / 5 (40.00%)
    13 / 22 (59.09%)
    7 / 12 (58.33%)
         occurrences all number
    4
    2
    3
    17
    8
    Eructation
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Flatulence
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Nausea
         subjects affected / exposed
    3 / 4 (75.00%)
    1 / 1 (100.00%)
    3 / 5 (60.00%)
    13 / 22 (59.09%)
    6 / 12 (50.00%)
         occurrences all number
    6
    1
    4
    17
    6
    Stomatitis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    3 / 22 (13.64%)
    2 / 12 (16.67%)
         occurrences all number
    2
    0
    0
    5
    3
    Vomiting
         subjects affected / exposed
    2 / 4 (50.00%)
    1 / 1 (100.00%)
    4 / 5 (80.00%)
    11 / 22 (50.00%)
    4 / 12 (33.33%)
         occurrences all number
    2
    1
    6
    15
    6
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Dermatitis bullous
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Photosensitivity reaction
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Rash
         subjects affected / exposed
    1 / 4 (25.00%)
    1 / 1 (100.00%)
    1 / 5 (20.00%)
    3 / 22 (13.64%)
    0 / 12 (0.00%)
         occurrences all number
    1
    1
    1
    3
    0
    Skin toxicity
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Renal failure
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    2 / 22 (9.09%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    1
    2
    1
    Back pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    3 / 22 (13.64%)
    3 / 12 (25.00%)
         occurrences all number
    0
    0
    0
    3
    3
    Muscular weakness
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Candiduria
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Catheter site cellulitis
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Genital herpes
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Influenza
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    2
    0
    Paronychia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Pyelonephritis
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Urinary tract infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    0
    2
    2
    Uterine infection
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    3 / 22 (13.64%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    1
    3
    0
    Dehydration
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Hypercalcaemia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    2 / 22 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    1
    2
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    2 / 22 (9.09%)
    2 / 12 (16.67%)
         occurrences all number
    0
    0
    0
    2
    2
    Hyperkalaemia
         subjects affected / exposed
    1 / 4 (25.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    0
    2
    0
    Hypernatraemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Hyperuricaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1
    Hypokalaemia
         subjects affected / exposed
    2 / 4 (50.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    3 / 22 (13.64%)
    0 / 12 (0.00%)
         occurrences all number
    4
    0
    1
    5
    0
    Hypomagnesaemia
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    1 / 5 (20.00%)
    1 / 22 (4.55%)
    0 / 12 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Increased appetite
         subjects affected / exposed
    0 / 4 (0.00%)
    0 / 1 (0.00%)
    0 / 5 (0.00%)
    1 / 22 (4.55%)
    1 / 12 (8.33%)
         occurrences all number
    0
    0
    0
    1
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    30 Nov 2015
    Clarified the inclusion criteria 2 for ALK positivity. A subject was to have a histologically or cytologically confirmed diagnosis of one of the tumors that was ALK- positive. The ALK test results were to be available at the Investigator site before the first dose of the study drug. The tumor types are described below: ALCL: local confirmation of diagnosis of ALK+ ALCL was sufficient for eligibility. IMT: local confirmation of translocation involving the ALK gene. GBM, IBC and any other locally documented ALK+ tumor were to carry a locally documented genetic alteration of ALK. Provided follow up evaluations for hepatic toxicities and work-up guidelines for potential Drug Induced Liver Injury (DILI) cases. Updated the exclusion criteria for contraception use. Dose guidance modification for QTcF text was updated to provide clarification on monitoring procedure. 

    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 03:54:31 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA