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   43871   clinical trials with a EudraCT protocol, of which   7290   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:
    Clinical Trial Phase IIB randomized, multicenter, of continuation or non-continuation with 6 cycles of temozolomide after the first 6 cycles of standard first-line treatment in patients with glioblastoma.

    Summary
    EudraCT number
    		 2014-000838-39
    Trial protocol
    		 ES  
    Global end of trial date
    14 Jun 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    05 Nov 2020
    First version publication date
    05 Nov 2020
    Other versions
    Summary report(s)
    		 Peer review journal publication

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GEINO14-01
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Grupo Español de Investigación en Neuro-Oncología (GEINO)
    Sponsor organisation address
    C/ Velázquez no7, 3 planta, Madrid, Spain, 28001
    Public contact
    Pau Doñate, MFAR Clinical Research, investigacion@mfar.net
    Scientific contact
    Pau Doñate, MFAR Clinical Research, investigacion@mfar.net
    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
    30 Sep 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    14 Jun 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Jun 2019
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Detect differences in the probability of progression-free survival at 6 months between patients with methylated or unmethylated MGMT and residual disease or not, to receive an additional 6 cycles of temozolomide.
    Protection of trial subjects
    The trial was conducted in accordance with applicable regulatory requirements and the principles of the Declaration of Helsinki. The protocol was approved by the ethics committees of all participating centers. All patients provided their signed informed consent.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    02 Sep 2014
    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: 159
    Worldwide total number of subjects
    159
    EEA total number of subjects
    159
    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)
    159
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 From August 22, 2014 to November 27, 2018 166 patients were recruited across 20 centers in Spain.

    Pre-assignment
    Screening details
    		 166 patients were screened, seven of whom were deemed to be ineligible. Seventy-nine patients were randomized to stop temozolomide after cycle 6 (control arm) and 80 to continue for up to six additional cycles (cycles 7 to 12) (experimental arm).

    Period 1
    Period 1 title
    Baseline (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    No blinding was empowered.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Control
    Arm description
    		 Patients will recieve no intervention, stop temozolomide after cycle 6
    Arm type
    		 No intervention

    Investigational medicinal product name
    No investigational medicinal product assigned in this arm
    Arm title
    		 Experimental arm
    Arm description
    		 Patients will receive 6 additional temozolomide cycles, a total of 12
    Arm type
    		 Experimental

    Investigational medicinal product name
    Temozolomide
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    150-200 mg/m2 Administered the first 5 days of a 28 days cycle

    Number of subjects in period 1
    		Control Experimental arm
    Started
    79
    80
    Completed
    40
    48
    Not completed
    39
    32
         Discontinued intervention due to progression
    39
    31
         Lost to follow-up
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Control
    Reporting group description
    		 Patients will recieve no intervention, stop temozolomide after cycle 6

    Reporting group title
    Experimental arm
    Reporting group description
    		 Patients will receive 6 additional temozolomide cycles, a total of 12

    Reporting group values
    		 Control Experimental arm Total
    Number of subjects
    		 79 80 159
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 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)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (full range (min-max))
    		 60.4 (31 to 79) 60.7 (29 to 83) -
    Gender categorical
    Units: Subjects
        Female
    		 38 38 76
        Male
    		 41 42 83
    Residual disease (>10mm)
    Units: Subjects
        Yes
    		 42 41 83
        No
    		 37 39 76
    KPS index
    Units: Subjects
        <70%
    		 2 2 4
        >=70%
    		 77 78 155
    Residual Neurological symptom
    Units: Subjects
        Yes
    		 8 19 27
        No
    		 71 60 131
        NA
    		 0 1 1
    DXM dose at inclusion
    Units: Subjects
        0 mg
    		 70 67 137
        0.5-2 mg
    		 6 9 15
        >2 mg
    		 3 4 7
    Barthel index
    Units: Subjects
        index 0
    		 9 12 21
        index 1
    		 70 68 138
    MMSE
    Units: Subjects
        index <27
    		 10 16 26
        index ≥27
    		 60 51 111
        NP / ND
    		 9 13 22
    Anticonvulsant therapy
    Units: Subjects
        Yes
    		 38 37 75
        No
    		 41 43 84
    Initial surgery-Treatment at diagnosis
    Units: Subjects
        Biopsy
    		 10 7 17
        Complete resection by post-op MRI)
    		 35 28 63
        Complete resection without post-op MRI
    		 14 20 34
        Subtotal resection
    		 20 25 45
    MGMT Methylation status
    Units: Subjects
        Methylated
    		 48 49 97
        Unmethylated
    		 31 31 62
    IDH1 Mutation status
    Units: Subjects
        IDH1-R132 mutated by ICH
    		 7 1 8
        IDH1-R132 non mutated by ICH
    		 66 71 137
        not determined
    		 6 8 14

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Control
    Reporting group description
    		 Patients will recieve no intervention, stop temozolomide after cycle 6

    Reporting group title
    Experimental arm
    Reporting group description
    		 Patients will receive 6 additional temozolomide cycles, a total of 12

    Primary: Progression free survival at 6 month

    		 Close Top of page
    End point title
    		 Progression free survival at 6 month
    End point description
    Number of patients (proportion) without progression of disease and time between start of treatment and progression of disease.
    End point type
    Primary
    End point timeframe
    6 months after the start of treatment (6 additional cycles of temozolomide for experimental arm or standard of care for control arm)
    End point values
    		 Control Experimental arm
    Number of subjects analysed
    79
    80
    Units: Percentage of subjects free of PD
        median (confidence interval 95%)
    55.7 (45.8 to 67.8)
    61.3 (51.5 to 72.9)
    Attachments
    		 PFS Kaplan Meier
    Statistical analysis title
    		 Log Rank (Mantel-Cox)
    Comparison groups
    Control v Experimental arm
    Number of subjects included in analysis
    159
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 ≤ 0.05 [1]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.71
         upper limit
    		 1.38
    Notes
    [1] - p values lower than 0.05 will point to discard the null hypothesis, which assumes no differences between treatment arms.

    Secondary: Treatment safety

    		 Close Top of page
    End point title
    		 Treatment safety
    End point description
    Total number of adverse events, type of events and grade. ONLY RELEVANT DIFFERENCES IN TOXICITY BY ARM
    End point type
    Secondary
    End point timeframe
    Through the whole study. 4 years
    End point values
    		 Control Experimental arm
    Number of subjects analysed
    79
    80
    Units: Number of patients
        Lymphopenia
    33
    55
        Thrombocytopenia
    17
    38
        Nausea and Vomiting
    10
    30
        Fatigue
    21
    35
        Leucopenia
    20
    30
    No statistical analyses for this end point

    Secondary: Progresion Free survival Median values

    		 Close Top of page
    End point title
    		 Progresion Free survival Median values
    End point description
    Progression free survival assessed by CT scan following the RANO criteria
    End point type
    Secondary
    End point timeframe
    Through the whole study. 4 years. The median follow up for each patient was 33.4 months
    End point values
    		 Control Experimental arm
    Number of subjects analysed
    79
    80
    Units: Months
        median (confidence interval 95%)
    7.77 (5.70 to 9.83)
    9.5 (5.93 to 13.07)
    Attachments
    		 PFS Kaplan Meier
    No statistical analyses for this end point

    Secondary: Overall Survival

    		 Close Top of page
    End point title
    		 Overall Survival
    End point description
    Time between start of treatment and death
    End point type
    Secondary
    End point timeframe
    Through the whole study. 4 years. The median follow up for each patient was 33.4 months.
    End point values
    		 Control Experimental arm
    Number of subjects analysed
    79
    80
    Units: Months
        median (confidence interval 95%)
    23.3 (17.9 to 28.7)
    18.2 (16.7 to 23.8)
    Attachments
    		 OS Kaplan Meier chart
    No statistical analyses for this end point

    Secondary: Translational sub-study - Biomarkers MSH6 immunoreactivity.

    		 Close Top of page
    End point title
    		 Translational sub-study - Biomarkers MSH6 immunoreactivity.
    End point description
    MSH6 immunoreactivity. partial immunoreactivity of MSH6 in patients by treatment arm
    End point type
    Secondary
    End point timeframe
    Baseline determination
    End point values
    		 Control Experimental arm
    Number of subjects analysed
    79
    80
    Units: Patients
        MSH6 partial immunoreactivity
    6
    5
        no MSH6 partial immunoreactivity
    73
    75
    No statistical analyses for this end point

    Secondary: Median PFS by arm and MGMT methylation status

    		 Close Top of page
    End point title
    		 Median PFS by arm and MGMT methylation status
    End point description
    Median Progression Free Survival depending on treatment arm in patients with MGMT methylation
    End point type
    Secondary
    End point timeframe
    Through the whole study. 4 years. The median follow up for each patient was 33.4 months
    End point values
    		 Control Experimental arm
    Number of subjects analysed
    48 [2]
    49 [3]
    Units: Months
        median (confidence interval 95%)
    8.5 (6.5 to 10.4)
    11.4 (9.2 to 13.6)
    Attachments
    		 PFS Kaplan Meier for patients with MGMT methylatio
    Notes
    [2] - Only patients with MGMT methylated
    [3] - Only patients with MGMT methylated
    No statistical analyses for this end point

    Secondary: Median OS by arm and MGMT methylation status

    		 Close Top of page
    End point title
    		 Median OS by arm and MGMT methylation status
    End point description
    Median OS depending on treatment arm in patients with methylated MGMT
    End point type
    Secondary
    End point timeframe
    Through the whole study. 4 years. The median follow up for each patient was 33.4 months
    End point values
    		 Control Experimental arm
    Number of subjects analysed
    48 [4]
    49 [5]
    Units: Months
        median (confidence interval 95%)
    27.1 (20.3 to 33.9)
    20.7 (14.7 to 26.7)
    Attachments
    		 OS Kaplan Meier for patients with MGMT methylation
    Notes
    [4] - Only patients with MGMT methylated
    [5] - Only patients with MGMT methylated
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Through the clinical study. About 4 years
    Adverse event reporting additional description
    In addition, clinically relevant changes on physical examination and abnormal parameters found on complementary examinations (eg radiography, ECG) should also be reported like AE.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 NCI CTCAE
    Dictionary version
    4.0
    Reporting groups
    Reporting group title
    Control
    Reporting group description
    		 Patients will recieve no intervention, stop temozolomide after cycle 6

    Reporting group title
    Experimental arm
    Reporting group description
    		 Patients will receive 6 additional temozolomide cycles, a total of 12

    Serious adverse events
    		 Control Experimental arm
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 79 (6.33%)
    9 / 80 (11.25%)
         number of deaths (all causes)
    52
    63
         number of deaths resulting from adverse events
    Vascular disorders
    Intra-craneal hypertension
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 80 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    claudication
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Dysarthria
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 80 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neurological impairment
         subjects affected / exposed
    0 / 79 (0.00%)
    2 / 80 (2.50%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Syncope
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 80 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General deterioration
         subjects affected / exposed
    1 / 79 (1.27%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 80 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Femur fracture
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Respiratory infection
         subjects affected / exposed
    0 / 79 (0.00%)
    1 / 80 (1.25%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1%
    Non-serious adverse events
    		 Control Experimental arm
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    79 / 79 (100.00%)
    80 / 80 (100.00%)
    Vascular disorders
    Thromboembolism
         subjects affected / exposed
    2 / 79 (2.53%)
    0 / 80 (0.00%)
         occurrences all number
    2
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    21 / 79 (26.58%)
    35 / 80 (43.75%)
         occurrences all number
    21
    35
    Anxiety
         subjects affected / exposed
    2 / 79 (2.53%)
    1 / 80 (1.25%)
         occurrences all number
    2
    1
    Pain
         subjects affected / exposed
    10 / 79 (12.66%)
    13 / 80 (16.25%)
         occurrences all number
    10
    13
    Respiratory, thoracic and mediastinal disorders
    Respiratory disorder
         subjects affected / exposed
    2 / 79 (2.53%)
    1 / 80 (1.25%)
         occurrences all number
    2
    1
    Cardiac disorders
    Cardiac events
         subjects affected / exposed
    1 / 79 (1.27%)
    0 / 80 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Neurologic impairment
         subjects affected / exposed
    41 / 79 (51.90%)
    38 / 80 (47.50%)
         occurrences all number
    41
    38
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    20 / 79 (25.32%)
    30 / 80 (37.50%)
         occurrences all number
    20
    30
    Neutropenia
         subjects affected / exposed
    2 / 79 (2.53%)
    3 / 80 (3.75%)
         occurrences all number
    2
    3
    Anemia
         subjects affected / exposed
    8 / 79 (10.13%)
    4 / 80 (5.00%)
         occurrences all number
    8
    4
    Lymphopenia
         subjects affected / exposed
    33 / 79 (41.77%)
    55 / 80 (68.75%)
         occurrences all number
    33
    55
    Thrombocytopenia
         subjects affected / exposed
    17 / 79 (21.52%)
    38 / 80 (47.50%)
         occurrences all number
    17
    38
    Alkaline phosphatase high
         subjects affected / exposed
    4 / 79 (5.06%)
    3 / 80 (3.75%)
         occurrences all number
    4
    3
    Potassium high
         subjects affected / exposed
    6 / 79 (7.59%)
    3 / 80 (3.75%)
         occurrences all number
    6
    3
    Sodium high
         subjects affected / exposed
    5 / 79 (6.33%)
    7 / 80 (8.75%)
         occurrences all number
    5
    7
    GGT high
         subjects affected / exposed
    6 / 79 (7.59%)
    4 / 80 (5.00%)
         occurrences all number
    6
    4
    GOT high
         subjects affected / exposed
    3 / 79 (3.80%)
    1 / 80 (1.25%)
         occurrences all number
    3
    1
    GPT high
         subjects affected / exposed
    7 / 79 (8.86%)
    5 / 80 (6.25%)
         occurrences all number
    7
    5
    Bilirubin high
         subjects affected / exposed
    8 / 79 (10.13%)
    7 / 80 (8.75%)
         occurrences all number
    8
    7
    Ear and labyrinth disorders
    Hearing loss
         subjects affected / exposed
    2 / 79 (2.53%)
    1 / 80 (1.25%)
         occurrences all number
    2
    1
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    10 / 79 (12.66%)
    30 / 80 (37.50%)
         occurrences all number
    10
    30
    Skin and subcutaneous tissue disorders
    Skin disorder
         subjects affected / exposed
    3 / 79 (3.80%)
    4 / 80 (5.00%)
         occurrences all number
    3
    4
    Renal and urinary disorders
    Creatinine urine
         subjects affected / exposed
    6 / 79 (7.59%)
    3 / 80 (3.75%)
         occurrences all number
    6
    3
    Musculoskeletal and connective tissue disorders
    Bone events
         subjects affected / exposed
    4 / 79 (5.06%)
    3 / 80 (3.75%)
         occurrences all number
    4
    3
    Infections and infestations
    Constipation
         subjects affected / exposed
    2 / 79 (2.53%)
    6 / 80 (7.50%)
         occurrences all number
    2
    6
    Infection
         subjects affected / exposed
    5 / 79 (6.33%)
    11 / 80 (13.75%)
         occurrences all number
    5
    11
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    19 / 79 (24.05%)
    14 / 80 (17.50%)
         occurrences all number
    19
    14
    Anorexia
         subjects affected / exposed
    1 / 79 (1.27%)
    4 / 80 (5.00%)
         occurrences all number
    1
    4

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Dec 2016
    Inclusion of 2 new centers

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/32328662
    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 May 02 12:17:53 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA