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    Clinical Trial Results:
    PHASE 2 SINGLE-ARM, OPEN LABEL STUDY OF IRINOTECAN IN COMBINATION WITH TEMOZOLOMIDE IN CHILDREN WITH RECURRENT OR REFRACTORY MEDULLOBLASTOMA AND IN CHILDREN WITH NEWLY DIAGNOSED HIGH-GRADE GLIOMA

    Due to a system error, the data reported in v1 is not correct and has been removed from public view.
    Summary
    EudraCT number
    2006-005476-40
    Trial protocol
    GB   FR   DK   IT   PL   ES  
    Global end of trial date
    15 Dec 2011

    Results information
    Results version number
    v2(current)
    This version publication date
    26 Mar 2016
    First version publication date
    30 Jul 2015
    Other versions
    v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    Correction of identified Timestamp error .

    Trial information

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    Trial identification
    Sponsor protocol code
    A5961166
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00404495
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Pfizer Inc
    Sponsor organisation address
    235 E 42nd Street, New York, United States, NY 10017
    Public contact
    Pfizer Clinical Trials.gov Call Centre, Pfizer Inc, 001800 7181021, ClinicalTrials.gov_Inquiries@pfizer.com
    Scientific contact
    Pfizer Clinical Trials.gov Call Centre, Pfizer Inc, 001800 7181021, ClinicalTrials.gov_Inquiries@pfizer.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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    02 May 2012
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    15 Dec 2011
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the rate of objective confirmed tumor response of irinotecan in combination with temozolomide in children with recurrent or refractory medulloblastoma and in children with newly diagnosed high-grade glioma.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    30 Apr 2007
    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: 13
    Country: Number of subjects enrolled
    United Kingdom: 20
    Country: Number of subjects enrolled
    Australia: 4
    Country: Number of subjects enrolled
    Belgium: 4
    Country: Number of subjects enrolled
    Denmark: 2
    Country: Number of subjects enrolled
    France: 30
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    Poland: 9
    Worldwide total number of subjects
    83
    EEA total number of subjects
    79
    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)
    61
    Adolescents (12-17 years)
    22
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

    Pre-assignment
    Screening details
    83 subjects were enrolled; 66 subjects were treated with Temozolomide + Irinotecan for medulloblastoma and 17 subjects were treated with Temozolomide + Irinotecan for high-grade glioma.

    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
    Temozolomide + Irinotecan for Medulloblastoma
    Arm description
    For subjects with medulloblastoma: Irinotecan 10 mg/m^2/Day on Days 1-5 and Days 8-12 in repeated 3-week cycles. Temozolomide 100-125 mg/m^2 daily on Days 1-5 in repeated 3-week cycles; treatment duration: up to 1 year or until progression.
    Arm type
    Experimental

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Irinotecan 10 milligram per square meter (mg/m^2) per Day on Days 1-5 and Days 8-12 in repeated 3 week cycles.

    Investigational medicinal product name
    Temozolomide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Temozolomide 100-125 mg/m^2 daily on Days 1-5 in repeated 3 week cycles.

    Arm title
    Temozolomide + Irinotecan for High-Grade Glioma
    Arm description
    For subjects with high-grade glioma: Irinotecan 10 mg/m^2/day on Days 1-5 and Days 8-12 in repeated 3-week cycles. Temozolomide 100-125 mg/m^2 daily on Days 1-5 in repeated 3-week cycles; treatment duration: 2 cycles as a window phase before starting standard therapy.
    Arm type
    Experimental

    Investigational medicinal product name
    Temozolomide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Temozolomide 100-125 mg/m^2 daily on Days 1-5 in repeated 3 week cycles.

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Irinotecan 10 mg/m^2 per Day on Days 1-5 and Days 8-12 in repeated 3 week cycles.

    Number of subjects in period 1
    Temozolomide + Irinotecan for Medulloblastoma Temozolomide + Irinotecan for High-Grade Glioma
    Started
    66
    17
    Completed
    22
    6
    Not completed
    44
    11
         Death
    37
    11
         Not specified
    1
    -
         Consent withdrawn by subject
    1
    -
         Lost to follow-up
    5
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Temozolomide + Irinotecan for Medulloblastoma
    Reporting group description
    For subjects with medulloblastoma: Irinotecan 10 mg/m^2/Day on Days 1-5 and Days 8-12 in repeated 3-week cycles. Temozolomide 100-125 mg/m^2 daily on Days 1-5 in repeated 3-week cycles; treatment duration: up to 1 year or until progression.

    Reporting group title
    Temozolomide + Irinotecan for High-Grade Glioma
    Reporting group description
    For subjects with high-grade glioma: Irinotecan 10 mg/m^2/day on Days 1-5 and Days 8-12 in repeated 3-week cycles. Temozolomide 100-125 mg/m^2 daily on Days 1-5 in repeated 3-week cycles; treatment duration: 2 cycles as a window phase before starting standard therapy.

    Reporting group values
    Temozolomide + Irinotecan for Medulloblastoma Temozolomide + Irinotecan for High-Grade Glioma Total
    Number of subjects
    66 17 83
    Age categorical
    Units: Subjects
        2 years to 12 years
    49 12 61
        Greater than (>) 12 years to 18 years
    17 5 22
    Gender categorical
    Units: Subjects
        Female
    21 3 24
        Male
    45 14 59

    End points

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    End points reporting groups
    Reporting group title
    Temozolomide + Irinotecan for Medulloblastoma
    Reporting group description
    For subjects with medulloblastoma: Irinotecan 10 mg/m^2/Day on Days 1-5 and Days 8-12 in repeated 3-week cycles. Temozolomide 100-125 mg/m^2 daily on Days 1-5 in repeated 3-week cycles; treatment duration: up to 1 year or until progression.

    Reporting group title
    Temozolomide + Irinotecan for High-Grade Glioma
    Reporting group description
    For subjects with high-grade glioma: Irinotecan 10 mg/m^2/day on Days 1-5 and Days 8-12 in repeated 3-week cycles. Temozolomide 100-125 mg/m^2 daily on Days 1-5 in repeated 3-week cycles; treatment duration: 2 cycles as a window phase before starting standard therapy.

    Primary: Percentage of Subjects With Objective Response of Complete Response or Partial Response

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    End point title
    Percentage of Subjects With Objective Response of Complete Response or Partial Response [1]
    End point description
    Percentage of subjects with objective response based assessment of confirmed complete response (CR) or confirmed partial response (PR). CR persisted on repeat imaging study at least (≥) 4 weeks after initial documentation of response. PR, for bidimensionally measurable disease, was a decrease by ≥50% of the sum of the products of the largest perpendicular diameters of all measurable lesions as determined by 2 observations not less than 4 weeks apart. Best overall response recorded any time while the subject was receiving treatment. External Response Review Committee (ERRC) assessment. Primary Evaluable Population: subset of evaluable population predetermined by 2-stage Optimum Simon design. Medulloblastoma cohort: n=consecutive evaluable subjects up to 46 if 6 responses obtained in first 15 evaluable subjects. Glioma cohort: n=consecutive evaluable subjects up to 29 if 1 response in first 10 evaluable subjects.
    End point type
    Primary
    End point timeframe
    Baseline to 1 Year (medulloblastoma), Baseline to 6 Weeks (high-grade glioma)
    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: Only descriptive data was planned to be collected for this endpoint. No statistical analysis was performed as per planned analysis. 
    End point values
    Temozolomide + Irinotecan for Medulloblastoma Temozolomide + Irinotecan for High-Grade Glioma
    Number of subjects analysed
    46
    10
    Units: percentage of subjects
        number (confidence interval 95%)
    32.6 (19.5 to 48)
    0 (0 to 30.8)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Objective Response of Complete Response or Partial Response, Investigator's Assessment

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    End point title
    Percentage of Subjects With Objective Response of Complete Response or Partial Response, Investigator's Assessment
    End point description
    Percentage of subjects with objective response based assessment of confirmed CR or confirmed PR. CR persisted on repeat imaging study ≥4 weeks after initial documentation of response. PR, in case of bidimensionally measurable disease, was a decrease by ≥50% of the sum of the products of the largest perpendicular diameters of all measurable lesions as determined by 2 observations not less than 4 weeks apart. Best overall response could be recorded any time while the subject was receiving treatment. Investigator's assessment. Evaluable local population: Subjects received at least 1 dose of study medication, had measurable disease under study, at least 1 on-study objective tumor assessment, completed at least 2 cycles of study treatment or progressed. Based on investigator's assessment.
    End point type
    Secondary
    End point timeframe
    Baseline to 1 Year (medulloblastoma), Baseline to 6 Weeks (high-grade glioma)
    End point values
    Temozolomide + Irinotecan for Medulloblastoma Temozolomide + Irinotecan for High-Grade Glioma
    Number of subjects analysed
    63
    17
    Units: percentage of subjects
        number (confidence interval 95%)
    34.9 (23.3 to 48)
    11.8 (1.5 to 36.4)
    No statistical analyses for this end point

    Secondary: Duration of Response

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    End point title
    Duration of Response
    End point description
    Median duration (50%) of tumor response for subjects with objective disease response: who have not progressed or died due to any cause; with a response and subsequent progression or death due to any cause for duration of response (DR). DR was defined as time from start of first documented objective tumor response (CR or PR) to first documented objective tumor progression or death due to any cause, whichever occurred first. DR (calculated in Weeks) = (the end date for DR minus first subsequent confirmed CR or PR plus 1) divided by 7. Investigator's assessment. Evaluable local population.
    End point type
    Secondary
    End point timeframe
    Baseline to Date of Tumor Response (Up to 1 Year)
    End point values
    Temozolomide + Irinotecan for Medulloblastoma Temozolomide + Irinotecan for High-Grade Glioma
    Number of subjects analysed
    22 [2]
    2 [3]
    Units: weeks
        median (full range (min-max))
    22.4 (6.9 to 46.6)
    36.3 (4 to 68.6)
    Notes
    [2] - Number of subjects analyzed=number of subjects who responded.
    [3] - Number of subjects analyzed=number of subjects who responded.
    No statistical analyses for this end point

    Secondary: Time to Treatment Failure (TTF)

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    End point title
    Time to Treatment Failure (TTF)
    End point description
    TTF was defined as the time from the date of first dose of study treatment to the date of the first documentation of progressive disease (PD), the date of treatment discontinuation except completion of treatment, or date of death due to cancer. Investigator's assessment. Evaluable local population was assessed.
    End point type
    Secondary
    End point timeframe
    Baseline to Date of Treatment Failure (Up to 1 Year)
    End point values
    Temozolomide + Irinotecan for Medulloblastoma Temozolomide + Irinotecan for High-Grade Glioma
    Number of subjects analysed
    63
    17
    Units: months
        median (confidence interval 95%)
    3.8 (2.9 to 5.4)
    1.6 (1.3 to 2.4)
    No statistical analyses for this end point

    Secondary: Time to Tumor Progression (TTP)

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    End point title
    Time to Tumor Progression (TTP)
    End point description
    TTP was defined as the time in months from start of study treatment to first documentation of objective tumor progression or death due to cancer, whichever came first. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 7 multiplied by 4.33. Tumor progression was determined from oncologic assessment data (where data met the criteria for PD). Investigator's assessment. Evaluable local population was analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline to Date of Progression (Up to 1 Year)
    End point values
    Temozolomide + Irinotecan for Medulloblastoma Temozolomide + Irinotecan for High-Grade Glioma
    Number of subjects analysed
    63
    17
    Units: months
        median (confidence interval 95%)
    5.6 (3.8 to 7.4)
    1.6 (1.3 to 7.5)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    Overall Survival (OS)
    End point description
    Time in months from the start of study treatment to date of death due to any cause. OS was calculated as (the death date minus the date of first dose of study medication plus 1) divided by 7 multiplied by 4.33. Death was determined from adverse event data (where outcome was death) or from follow-up contact data (where the subject current status was death). Investigator's assessment. All subjects were analyzed. One subject in the Temozolomide + Irinotecan for Medulloblastoma cohort did not have recurrent or refractory medulloblastoma and 3 subjects in the Temozolomide + Irinotecan for High-Grade Glioma cohort did not have high-grade glioma, and were not considered evaluable for survival.
    End point type
    Secondary
    End point timeframe
    Baseline to Date of Death (Up to 1 Year After Treatment)
    End point values
    Temozolomide + Irinotecan for Medulloblastoma Temozolomide + Irinotecan for High-Grade Glioma
    Number of subjects analysed
    65
    14
    Units: months
        median (confidence interval 95%)
    16.7 (13.3 to 19.8)
    9.4 (5.8 to 20.2)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Treatment emergent adverse events are reported from time of first dose of study treatment up to 30 days after last dose of study treatment .
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Temozolomide + Irinotecan for Medulloblastoma
    Reporting group description
    For subjects with medulloblastoma: Irinotecan 10 mg/m^2/day on Days 1-5 and Days 8-12 in repeated 3-week cycles. Temozolomide 100-125 mg/m^2 daily on Days 1-5 in repeated 3-week cycles; treatment duration: up to 1 year or until progression.

    Reporting group title
    Temozolomide + Irinotecan for High-Grade Glioma
    Reporting group description
    For subjects with high-grade glioma: Irinotecan 10 mg/m^2/day on Days 1-5 and Days 8-12 in repeated 3-week cycles. Temozolomide 100-125 mg/m^2 daily on Days 1-5 in repeated 3-week cycles; treatment duration: 2 cycles as a window phase before starting standard therapy.

    Serious adverse events
    Temozolomide + Irinotecan for Medulloblastoma Temozolomide + Irinotecan for High-Grade Glioma
    Total subjects affected by serious adverse events
         subjects affected / exposed
    31 / 66 (46.97%)
    5 / 17 (29.41%)
         number of deaths (all causes)
    7
    2
         number of deaths resulting from adverse events
    0
    0
    Vascular disorders
    Hypotension
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angiopathy
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Blood culture positive
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Medulloblastoma
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Respiratory disorder
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Complex partial seizures
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    3 / 66 (4.55%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotonia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hydrocephalus
         subjects affected / exposed
    3 / 66 (4.55%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intracranial pressure increased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Coma
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    4 / 66 (6.06%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    1 / 6
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device occlusion
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    4 / 66 (6.06%)
    2 / 17 (11.76%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 2
         deaths causally related to treatment / all
    0 / 4
    0 / 2
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    6 / 66 (9.09%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    8 / 8
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proctalgia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (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: 0%
    Non-serious adverse events
    Temozolomide + Irinotecan for Medulloblastoma Temozolomide + Irinotecan for High-Grade Glioma
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    64 / 66 (96.97%)
    17 / 17 (100.00%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Haematoma
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Hypertension
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Hot flush
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Hypotension
         subjects affected / exposed
    4 / 66 (6.06%)
    1 / 17 (5.88%)
         occurrences all number
    7
    1
    Orthostatic hypotension
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Pallor
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour associated fever
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Melanocytic naevus
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Skin papilloma
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Asthenia
         subjects affected / exposed
    6 / 66 (9.09%)
    2 / 17 (11.76%)
         occurrences all number
    6
    2
    Catheter site rash
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Catheter site pain
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Catheter site swelling
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Device occlusion
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Fatigue
         subjects affected / exposed
    15 / 66 (22.73%)
    4 / 17 (23.53%)
         occurrences all number
    18
    4
    Chest pain
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Feeling abnormal
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Gait disturbance
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Feeling hot
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Inflammation
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    General physical health deterioration
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Mucosal inflammation
         subjects affected / exposed
    1 / 66 (1.52%)
    2 / 17 (11.76%)
         occurrences all number
    1
    2
    Pain
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Peripheral swelling
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
         subjects affected / exposed
    14 / 66 (21.21%)
    2 / 17 (11.76%)
         occurrences all number
    15
    2
    Xerosis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Agitation
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Confusional state
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Anxiety
         subjects affected / exposed
    1 / 66 (1.52%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    Depression
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Disorientation
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Insomnia
         subjects affected / exposed
    4 / 66 (6.06%)
    0 / 17 (0.00%)
         occurrences all number
    5
    0
    Nightmare
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    5
    0
    Reproductive system and breast disorders
    Genital lesion
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Penis disorder
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Vulvovaginal discomfort
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Animal bite
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Contusion
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    5
    0
    Fall
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Ligament sprain
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Head injury
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Stoma site pain
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Post procedural discharge
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Skin abrasion
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Wound
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    5 / 66 (7.58%)
    1 / 17 (5.88%)
         occurrences all number
    22
    1
    Alanine aminotransferase
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Blood bicarbonate decreased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Aspartate aminotransferase
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    5
    0
    Blood bicarbonate increased
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    6
    0
    Blood creatinine increased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Blood culture positive
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Blood magnesium decreased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Blood phosphorus decreased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Blood urea decreased
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    4
    0
    Blood potassium decreased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    12
    0
    C-reactive protein increased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Haemoglobin decreased
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Heart rate
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Haemoglobin
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Monocyte count decreased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Neutrophil count decreased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Protein total increased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Platelet count
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Platelet count decreased
         subjects affected / exposed
    1 / 66 (1.52%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    Weight increased
         subjects affected / exposed
    1 / 66 (1.52%)
    2 / 17 (11.76%)
         occurrences all number
    1
    2
    Weight decreased
         subjects affected / exposed
    6 / 66 (9.09%)
    0 / 17 (0.00%)
         occurrences all number
    12
    0
    Cardiac disorders
    Bradycardia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Sinus tachycardia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Congenital, familial and genetic disorders
    Aplasia
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Cough
         subjects affected / exposed
    13 / 66 (19.70%)
    0 / 17 (0.00%)
         occurrences all number
    21
    0
    Dyspnoea
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Hypoxia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Epistaxis
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Hiccups
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Pharyngeal erythema
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Nasal congestion
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    6 / 66 (9.09%)
    0 / 17 (0.00%)
         occurrences all number
    7
    0
    Rhinalgia
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Respiratory disorder
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    5 / 66 (7.58%)
    0 / 17 (0.00%)
         occurrences all number
    6
    0
    Blood and lymphatic system disorders
    Eosinopenia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Anaemia
         subjects affected / exposed
    10 / 66 (15.15%)
    1 / 17 (5.88%)
         occurrences all number
    40
    1
    Leukopenia
         subjects affected / exposed
    6 / 66 (9.09%)
    0 / 17 (0.00%)
         occurrences all number
    39
    0
    Lymphadenopathy
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Febrile neutropenia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Lymphopenia
         subjects affected / exposed
    10 / 66 (15.15%)
    0 / 17 (0.00%)
         occurrences all number
    62
    0
    Neutropenia
         subjects affected / exposed
    15 / 66 (22.73%)
    1 / 17 (5.88%)
         occurrences all number
    41
    6
    Thrombocytopenia
         subjects affected / exposed
    17 / 66 (25.76%)
    1 / 17 (5.88%)
         occurrences all number
    54
    2
    Nervous system disorders
    Ataxia
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Aphasia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Balance disorder
         subjects affected / exposed
    5 / 66 (7.58%)
    0 / 17 (0.00%)
         occurrences all number
    5
    0
    Cerebellar syndrome
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Cholinergic syndrome
         subjects affected / exposed
    1 / 66 (1.52%)
    1 / 17 (5.88%)
         occurrences all number
    2
    1
    Cranial nerve disorder
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Convulsion
         subjects affected / exposed
    4 / 66 (6.06%)
    0 / 17 (0.00%)
         occurrences all number
    5
    0
    Cranial nerve paralysis
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Dysarthria
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Dizziness
         subjects affected / exposed
    6 / 66 (9.09%)
    1 / 17 (5.88%)
         occurrences all number
    6
    1
    Hydrocephalus
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    4
    0
    Hemiparesis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    20 / 66 (30.30%)
    5 / 17 (29.41%)
         occurrences all number
    35
    7
    IIIrd nerve paralysis
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Hyperreflexia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Hypoaesthesia
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Intracranial pressure increased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Lethargy
         subjects affected / exposed
    4 / 66 (6.06%)
    0 / 17 (0.00%)
         occurrences all number
    4
    0
    Meningeal disorder
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Monoparesis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Muscle spasticity
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    2
    Migraine
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Neuralgia
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Neurological symptom
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Neuropathy peripheral
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Nystagmus
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Paraesthesia
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Partial seizures
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Peripheral motor neuropathy
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Presyncope
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Pyramidal tract syndrome
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Reflexes abnormal
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Slow speech
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Sensory disturbance
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Tardive dyskinesia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Syncope
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Somnolence
         subjects affected / exposed
    5 / 66 (7.58%)
    1 / 17 (5.88%)
         occurrences all number
    6
    1
    Visual field defect
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Tonic convulsion
         subjects affected / exposed
    1 / 66 (1.52%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    Tremor
         subjects affected / exposed
    2 / 66 (3.03%)
    1 / 17 (5.88%)
         occurrences all number
    2
    1
    Eye disorders
    Diplopia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Conjunctival hyperaemia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Eye pain
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Eye movement disorder
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Eyelid ptosis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Strabismus
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Keratitis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Lacrimation increased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Visual acuity reduced
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Ear and labyrinth disorders
    Ear canal erythema
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Deafness
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Ear pain
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Tinnitus
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Hypoacusis
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Vertigo
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Abdominal pain
         subjects affected / exposed
    22 / 66 (33.33%)
    4 / 17 (23.53%)
         occurrences all number
    50
    4
    Anal erosion
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Abdominal pain upper
         subjects affected / exposed
    8 / 66 (12.12%)
    1 / 17 (5.88%)
         occurrences all number
    9
    1
    Anal haemorrhage
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Anal fissure
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Aphthous stomatitis
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Breath odour
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    22 / 66 (33.33%)
    4 / 17 (23.53%)
         occurrences all number
    32
    5
    Faecal incontinence
         subjects affected / exposed
    1 / 66 (1.52%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    Diarrhoea
         subjects affected / exposed
    38 / 66 (57.58%)
    10 / 17 (58.82%)
         occurrences all number
    136
    12
    Dyspepsia
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Gastrointestinal ulcer
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Gingival bleeding
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Gastritis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Nausea
         subjects affected / exposed
    20 / 66 (30.30%)
    7 / 17 (41.18%)
         occurrences all number
    45
    12
    Mouth ulceration
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Lip oedema
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Oral mucosal eruption
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Oral pain
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Odynophagia
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Proctalgia
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Retching
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Salivary hypersecretion
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Stomatitis
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    6
    0
    Toothache
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    4
    0
    Vomiting
         subjects affected / exposed
    42 / 66 (63.64%)
    13 / 17 (76.47%)
         occurrences all number
    106
    36
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    4 / 66 (6.06%)
    0 / 17 (0.00%)
         occurrences all number
    4
    0
    Urinary retention
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Pollakiuria
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Urinary incontinence
         subjects affected / exposed
    1 / 66 (1.52%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    Urine flow decreased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Urogenital haemorrhage
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Alopecia
         subjects affected / exposed
    2 / 66 (3.03%)
    1 / 17 (5.88%)
         occurrences all number
    2
    1
    Dry skin
         subjects affected / exposed
    4 / 66 (6.06%)
    1 / 17 (5.88%)
         occurrences all number
    5
    1
    Decubitus ulcer
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Dermatitis
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Ecchymosis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Erythema
         subjects affected / exposed
    1 / 66 (1.52%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    Hyperhidrosis
         subjects affected / exposed
    1 / 66 (1.52%)
    2 / 17 (11.76%)
         occurrences all number
    1
    2
    Petechiae
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Nail disorder
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Ingrowing nail
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Pruritus generalised
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Pruritus
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Rash macular
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Rash pruritic
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Rash
         subjects affected / exposed
    5 / 66 (7.58%)
    1 / 17 (5.88%)
         occurrences all number
    6
    1
    Skin hyperpigmentation
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Skin striae
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Skin fissures
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Urticaria
         subjects affected / exposed
    1 / 66 (1.52%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    Musculoskeletal and connective tissue disorders
    Arthropathy
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Arthralgia
         subjects affected / exposed
    2 / 66 (3.03%)
    1 / 17 (5.88%)
         occurrences all number
    3
    1
    Back pain
         subjects affected / exposed
    7 / 66 (10.61%)
    0 / 17 (0.00%)
         occurrences all number
    9
    0
    Bone pain
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Joint range of motion decreased
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Limb discomfort
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Muscle spasms
         subjects affected / exposed
    4 / 66 (6.06%)
    0 / 17 (0.00%)
         occurrences all number
    4
    0
    Joint swelling
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Muscular weakness
         subjects affected / exposed
    3 / 66 (4.55%)
    1 / 17 (5.88%)
         occurrences all number
    3
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Myalgia
         subjects affected / exposed
    1 / 66 (1.52%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    Musculoskeletal pain
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Musculoskeletal stiffness
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Pain in jaw
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Pain in extremity
         subjects affected / exposed
    9 / 66 (13.64%)
    1 / 17 (5.88%)
         occurrences all number
    14
    1
    Neck pain
         subjects affected / exposed
    5 / 66 (7.58%)
    0 / 17 (0.00%)
         occurrences all number
    7
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    11 / 66 (16.67%)
    2 / 17 (11.76%)
         occurrences all number
    17
    2
    Hyperalbuminaemia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Hyperglycaemia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Dehydration
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Hypocalcaemia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    5
    0
    Hypochloraemia
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    7
    0
    Hypermagnesaemia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Hypokalaemia
         subjects affected / exposed
    4 / 66 (6.06%)
    0 / 17 (0.00%)
         occurrences all number
    16
    0
    Hypomagnesaemia
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Hyponatraemia
         subjects affected / exposed
    5 / 66 (7.58%)
    0 / 17 (0.00%)
         occurrences all number
    9
    0
    Hypophagia
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Hypophosphataemia
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    7
    0
    Malnutrition
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Bronchitis
         subjects affected / exposed
    0 / 66 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    Conjunctivitis
         subjects affected / exposed
    5 / 66 (7.58%)
    1 / 17 (5.88%)
         occurrences all number
    5
    1
    Ear infection
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Device related infection
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Herpes zoster
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Hordeolum
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Infection
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Nasopharyngitis
         subjects affected / exposed
    8 / 66 (12.12%)
    3 / 17 (17.65%)
         occurrences all number
    14
    3
    Oral herpes
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Oral candidiasis
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Pharyngitis
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Rhinitis
         subjects affected / exposed
    2 / 66 (3.03%)
    1 / 17 (5.88%)
         occurrences all number
    2
    1
    Sinusitis
         subjects affected / exposed
    2 / 66 (3.03%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Upper respiratory tract infection
         subjects affected / exposed
    7 / 66 (10.61%)
    0 / 17 (0.00%)
         occurrences all number
    10
    0
    Urinary tract infection
         subjects affected / exposed
    5 / 66 (7.58%)
    2 / 17 (11.76%)
         occurrences all number
    9
    2
    Tonsillitis
         subjects affected / exposed
    1 / 66 (1.52%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    Viral infection
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    Viral rhinitis
         subjects affected / exposed
    1 / 66 (1.52%)
    0 / 17 (0.00%)
         occurrences all number
    2
    0
    Viral upper respiratory tract infection
         subjects affected / exposed
    3 / 66 (4.55%)
    0 / 17 (0.00%)
         occurrences all number
    3
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Mar 2007
    1) Subjects who had response or achieved SD with temozolomide were eligible to receive irinotecan added to this temozolomide treatment (from first cycle of adjuvant chemotherapy) for maximum period of 1 year until disease progression, unacceptable toxicity, or subject’s desire to discontinue therapy, following radiotherapy and/or surgery, or other supportive care. 2) Inclusion criterion modified such that investigators could allow for effect of motor paresis due to disease in assessment in children with relatively stable neurological deficits. 3) Additional exclusion criteria on hypersensitivity/intolerance added. 5) Pathological Assessment section was added: For all high-grade glioma (HGG) subjects, pathological samples used for diagnosis were to be reviewed by a central pathologist. For recurrent medulloblastoma subjects in Cohort 1, pathological samples from initial diagnosis and/or a subsequent biopsy or resection were also reviewed if available. Rebiopsy at relapse not mandated. Central pathologist diagonosis used to determine evaluability. 6) For HGG subjects following 2 cycles of treatment, nonresponders were to discontinue study treatment and be treated with standard therapy. 7) HGG subjects with measurable residual disease were to have this confirmed by a post operative magnetic resonance imaging (MRI) performed within 72 hours of surgery. Subjects were to have a screening scan dated no more than 14 days prior treatment.
    25 Apr 2007
    1) Under Exclusion Criteria, chronic inflammatory bowel disease and/or bowel obstruction was added.
    24 Apr 2009
    1) This protocol was amended to clarify the maximum time any subject was permitted on treatment and to clarify the duration of post-treatment follow-up. 2) For subjects with recurrent or refractory medulloblastoma, treatment continued (for a maximum of 1 year) until disease progression, unacceptable toxicity, or the subject’s desire to discontinue therapy. 3) Subjects were followed up every 3 months for 1 year or until death or lost to follow-up.

    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.
    This study had one treatment arm but two distinct cohorts with different diagnostics and treatment durations.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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