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   43865   clinical trials with a EudraCT protocol, of which   7286   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:
    INVESTIGATION OF THE EFFICACY OF LAPATINIB PLUS TEMOZOLOMIDE COMBINATION, IN RECURRENT HIGH GRADE GLIOMAS. A PHASE I/II STUDY.

    Summary
    EudraCT number
    		 2007-006656-19
    Trial protocol
    		 GR  
    Global end of trial date
    02 Oct 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Jun 2019
    First version publication date
    30 Jun 2019
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    HE 17/08
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 ACTRN: ACTRN12611000418976
    Sponsors
    Sponsor organisation name
    Hellenic Cooperative Oncology Group
    Sponsor organisation address
    Hatzikostandi 18, Athens, Greece, 11524
    Public contact
    Hellenic Cooperative Oncology Group, Hellenic Cooperative Oncology Group, hecogoff@otenet.gr
    Scientific contact
    Hellenic Cooperative Oncology Group, Hellenic Cooperative Oncology Group, hecogoff@otenet.gr
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    14 Nov 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    02 Oct 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Phase I:The main objective is to determine the maximum tolerated dose and recommended phase II dose of lapatinib when given in combination with temozolomide in patients with recurrent or refractory glioblastoma multiforme and to assess the safety, tolerability and toxicity profile of this regimen in these patients. Phase II:The primary objective is to evaluate the activity of lapatinib/temozolomide combination in patients with recurrent high-grade gliomas by determining the optimal response to treatment.
    Protection of trial subjects
    This study was conducted in conformance with ICH GCP, all applicable laws and regulations. All participants were required to read and sign an Informed Consent Form.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    12 Jan 2009
    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
    Greece: 30
    Worldwide total number of subjects
    30
    EEA total number of subjects
    30
    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)
    22
    From 65 to 84 years
    8
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Participants were enrolled in the study from 12 January 2009 until 21 January 2013 from 4 sites in Greece.

    Pre-assignment
    Screening details
    		 All potentially eligible subjects underwent screening in order to confirm that all eligibility criteria were met prior to the first administration of the study treatment.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Phase I
    Arm description
    		 In the phase I study patients will be enrolled in cohorts of 3. They will receive fixed dose temozolomide [200 mg/m2 orally (po) once daily for 5 days] in cycles of 28 days and escalating doses of lapatinib. The starting dose of lapatinib will be 1000 mg administered orally (po) once daily (OD) every day of the 28 day cycle. Three dose levels of lapatinib will be explored (1000, 1250 and 1500 mg). Patients will receive lapatinib/ temozolomide combination until disease progression or unacceptable toxicity. Cohorts of 3 patients will receive escalating doses of lapatinib until the maximum tolerated dose is determined (MTD) as recorded in week 4 of treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lapatinib
    Investigational medicinal product code
    GW572016
    Other name
    Tyverb, lapatinib ditosylate monohydrate
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Cohort 1 Lapatinib 1000 mg/d for 28 d + temozolomide 200 mg/m2 d 1-5 q28d Cohort 2 Lapatinib 1250 mg/d for 28 d + temozolomide 200 mg/m2 d 1-5 q28d Cohort 3 Lapatinib 1500 mg/d for 28 d + temozolomide 200 mg/m2 d 1-5 q28d

    Arm title
    		 Phase II
    Arm description
    		 Patients received lapatinib 1000 mg (recommended dose resulting from Phase I of the study) orally once a day and temozolomide 200 mg / m2 once daily for 5 days in 28-day cycles. Treatment continued until disease progression, occurrence of unacceptable toxicity or withdrawal of consent by the patient.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lapatinib
    Investigational medicinal product code
    GW572016
    Other name
    Tyverb, lapatinib ditosylate monohydrate
    Pharmaceutical forms
    Coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Temozolomide 200 mg/m2 orally (po) once daily for 5 days along with Lapatinib 1000 mg orally (po) once daily (dose as defined from phase I). The cycle duration was 28 days. Treatment continued until disease progression, unacceptable toxicity or consent withdrawal.

    Number of subjects in period 1
    		Phase I Phase II
    Started
    16
    14
    Completed
    12
    0
    Not completed
    4
    14
         Clinical progression
    -
    1
         Disease progression
    1
    -
         Adverse event, non-fatal
    2
    -
         Death
    -
    1
         Progression
    -
    12
         Protocol deviation
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Phase I
    Reporting group description
    		 In the phase I study patients will be enrolled in cohorts of 3. They will receive fixed dose temozolomide [200 mg/m2 orally (po) once daily for 5 days] in cycles of 28 days and escalating doses of lapatinib. The starting dose of lapatinib will be 1000 mg administered orally (po) once daily (OD) every day of the 28 day cycle. Three dose levels of lapatinib will be explored (1000, 1250 and 1500 mg). Patients will receive lapatinib/ temozolomide combination until disease progression or unacceptable toxicity. Cohorts of 3 patients will receive escalating doses of lapatinib until the maximum tolerated dose is determined (MTD) as recorded in week 4 of treatment.

    Reporting group title
    Phase II
    Reporting group description
    		 Patients received lapatinib 1000 mg (recommended dose resulting from Phase I of the study) orally once a day and temozolomide 200 mg / m2 once daily for 5 days in 28-day cycles. Treatment continued until disease progression, occurrence of unacceptable toxicity or withdrawal of consent by the patient.

    Reporting group values
    		 Phase I Phase II Total
    Number of subjects
    		 16 14 30
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 10 12 22
        From 65-84 years
    		 6 2 8
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 60.3 (43.1 to 79.1) 47.3 (25.7 to 68.5) -
    Gender categorical
    Units: Subjects
        Female
    		 7 4 11
        Male
    		 9 10 19

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Phase I
    Reporting group description
    		 In the phase I study patients will be enrolled in cohorts of 3. They will receive fixed dose temozolomide [200 mg/m2 orally (po) once daily for 5 days] in cycles of 28 days and escalating doses of lapatinib. The starting dose of lapatinib will be 1000 mg administered orally (po) once daily (OD) every day of the 28 day cycle. Three dose levels of lapatinib will be explored (1000, 1250 and 1500 mg). Patients will receive lapatinib/ temozolomide combination until disease progression or unacceptable toxicity. Cohorts of 3 patients will receive escalating doses of lapatinib until the maximum tolerated dose is determined (MTD) as recorded in week 4 of treatment.

    Reporting group title
    Phase II
    Reporting group description
    		 Patients received lapatinib 1000 mg (recommended dose resulting from Phase I of the study) orally once a day and temozolomide 200 mg / m2 once daily for 5 days in 28-day cycles. Treatment continued until disease progression, occurrence of unacceptable toxicity or withdrawal of consent by the patient.

    Primary: Maximum Tolerated Dose of Lapatinib (L)

    		 Close Top of page
    End point title
    		 Maximum Tolerated Dose of Lapatinib (L) [1] [2]
    End point description
    Determine the maximum tolerated dose and recommended phase II dose of lapatinib (L) when given in combination with temozolomide (T) in patients with recurrent or refractory glioblastoma multiforme.
    End point type
    Primary
    End point timeframe
    Three dose levels of lapatinib were explored (1000, 1250 and 1500 mg). Patients received lapatinib (L)/ temozolomide (T) combination until disease progression or unacceptable toxicity.
    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: Descriptive statistics including the number of patients for each dose level of the phase I were used.
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The determination of the maximum tolerated dose was the primary endpoint of the phase I part of the trial. Therefore, the number of patients in each dose level was provided. The number of patients with dose limiting toxicities was also noted in the provided table.
    End point values
    		 Phase I
    Number of subjects analysed
    16 [3]
    Units: number of subjects entered per dose leve
        Level 1: T (200mg/m2), L (1000 mg)
    11
        Level 2: T (200 mg/m2), L (1250 mg) (2 DLTs)
    4
        Level 3: T (200 mg/m2), L (1500 mg)
    1
    Notes
    [3] - Patient in level 3 was enrolled prior to previous level's toxicity evaluation (protocol violation).
    No statistical analyses for this end point

    Primary: Activity of lapatinib/temozolomide

    		 Close Top of page
    End point title
    		 Activity of lapatinib/temozolomide [4] [5]
    End point description
    The primary objective of the Phase II was to evaluate the activity of lapatinib/temozolomide combination in patients with recurrent high-grade gliomas by determining the optimal response to treatment.
    End point type
    Primary
    End point timeframe
    MRI scans carried out at baseline, at the end of week 8, and every 8 weeks thereafter until progression, unacceptable toxicity or consent withdrawal.
    Notes
    [4] - 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: Since this was a single arm phase I/II trial and all patients were treated with lapatinib and temozolomide, no comparisons between different treatment groups could be performed. Descriptive statistics including the frequencies of best responses achieved are provided for all patients enrolled in phase II.
    [5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The activity of lapatinib/temozolomide was the primary endpoint of the phase II part of the study. Thus, the frequencies of best responses achieved are provided for all patients enrolled in phase II.
    End point values
    		 Phase II
    Number of subjects analysed
    14 [6]
    Units: number of patients
        Complete response
    0
        Partial response
    1
        Stable disease
    7
        Progressive disease
    5
        Not evaluable
    1
    Notes
    [6] - Enrollment was halted upon 13th patient's entry. 1 more patient was enrolled-registration violation.
    No statistical analyses for this end point

    Secondary: Safety and Toxicity profile

    		 Close Top of page
    End point title
    		 Safety and Toxicity profile
    End point description
    Determine the safety and tolerability (toxicity profile) of this regimen.
    End point type
    Secondary
    End point timeframe
    Adverse Events (AEs) (hematological and non-hematological toxicities) of all participants were recorded and assessed upon signature of the informed consent form until 30 days after the last administration of study.
    End point values
    		 Phase I Phase II
    Number of subjects analysed
    16
    14
    Units: number of patients
        Any adverse event
    16
    12
        Fatal adverse events
    0
    1
        Serious adverse events
    7
    3
    No statistical analyses for this end point

    Secondary: Time to progression (TTP)

    		 Close Top of page
    End point title
    		 Time to progression (TTP) [7]
    End point description
    End point type
    Secondary
    End point timeframe
    TTP was calculated from date of treatment initiation until tumor progression or last contact, whichever occurred first.
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Time to progression was a secondary endpoint of the phase II part of the trial. Therefore, the median TTP with the corresponding 95% confidence interval was provided for all phase II patients.
    End point values
    		 Phase II
    Number of subjects analysed
    14
    Units: months
        median (confidence interval 95%)
    4.3 (1.4 to 6.9)
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS) [8]
    End point description
    End point type
    Secondary
    End point timeframe
    OS was calculated from the date of treatment initiation to the date of death or last contact.
    Notes
    [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Overall survival was a secondary endpoint of the phase II part of the trial. Therefore, the median overall survival with the corresponding 95% confidence interval was provided for all phase II patients.
    End point values
    		 Phase II
    Number of subjects analysed
    14
    Units: months
        median (confidence interval 95%)
    10.2 (5.1 to 11.3)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse Events (AEs) (hematological and non-hematological toxicities) of all participants were recorded and assessed upon signature of the inform consent form until 30 days after last administration of study treatment.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    10
    Reporting groups
    Reporting group title
    Phase 1
    Reporting group description
    		 Temozolomide was administered at a fixed dose of 200 mg/m2 p.o. (d 1-5 q28d). Patients were advised to take temozolomide on an empty stomach (either 1 hour before or 1 hour after meals). Up to 3 dose levels of lapatinib were explored (1000, 1250, 1500 mg), in cohorts of at least 3 patients, as described in the trial design section. Patients were advised to take lapatinib on an empty stomach (either 1 hour before or 1 hour after meals).

    Reporting group title
    Phase 2
    Reporting group description
    		 Patients received lapatinib 1000 mg (recommended dose resulting from Phase I of the study) orally once a day and temozolomide 200 mg / m2 once daily for 5 days in 28-day cycles. Treatment continued until disease progression, occurrence of unacceptable toxicity or withdrawal of consent by the patient.

    Serious adverse events
    		 Phase 1 Phase 2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    7 / 16 (43.75%)
    3 / 14 (21.43%)
         number of deaths (all causes)
    16
    10
         number of deaths resulting from adverse events
    0
    1
    Investigations
    Haemoglobin decreased
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiopulmonary failure
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain head
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Somnolence
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Brain edema
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         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
    Disease progression
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombopenia
         subjects affected / exposed
    4 / 16 (25.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    4 / 4
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Leucopenia
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Diplopia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Psychiatric disorders
    Confusion
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Speech disorder
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Infection
    Additional description: Septic shock
         subjects affected / exposed
    2 / 16 (12.50%)
    1 / 14 (7.14%)
         occurrences causally related to treatment / all
    2 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Phase 1 Phase 2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    16 / 16 (100.00%)
    12 / 14 (85.71%)
    General disorders and administration site conditions
    Unsteady gait
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 14 (7.14%)
         occurrences all number
    1
    1
    Fatigue
         subjects affected / exposed
    5 / 16 (31.25%)
    2 / 14 (14.29%)
         occurrences all number
    8
    2
    Mucositis
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Fever
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    Oedema
    Additional description: Limb
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Abnormal gait
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    Flu-like syndrome
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Bloody vaginal discharge
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Hot flush
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Choking sensation
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Nasal congestion
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Hiccups
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Anxiety
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Sleep disorder
    Additional description: Reversal sleeping
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Investigations
    Haemoglobin
         subjects affected / exposed
    6 / 16 (37.50%)
    4 / 14 (28.57%)
         occurrences all number
    37
    16
    Leukocyte count decreased
         subjects affected / exposed
    5 / 16 (31.25%)
    3 / 14 (21.43%)
         occurrences all number
    36
    13
    Neutrophil count decreased
         subjects affected / exposed
    5 / 16 (31.25%)
    1 / 14 (7.14%)
         occurrences all number
    26
    7
    Platelet count decreased
         subjects affected / exposed
    7 / 16 (43.75%)
    4 / 14 (28.57%)
         occurrences all number
    57
    9
    Alkaline phosphatase increased
         subjects affected / exposed
    3 / 16 (18.75%)
    0 / 14 (0.00%)
         occurrences all number
    9
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    5 / 16 (31.25%)
    4 / 14 (28.57%)
         occurrences all number
    14
    5
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 16 (18.75%)
    2 / 14 (14.29%)
         occurrences all number
    9
    2
    Blood bilirubin increased
         subjects affected / exposed
    6 / 16 (37.50%)
    1 / 14 (7.14%)
         occurrences all number
    12
    1
    Cholesterol high
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 14 (7.14%)
         occurrences all number
    1
    1
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 14 (0.00%)
         occurrences all number
    4
    0
    Creatinine
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    LDH
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Nervous system disorders
    Burning sensation
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Dizziness
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 14 (0.00%)
         occurrences all number
    3
    0
    Memory impairment
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 14 (7.14%)
         occurrences all number
    1
    1
    Sensory neuropathy
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Seizure
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Somnolence
         subjects affected / exposed
    3 / 16 (18.75%)
    3 / 14 (21.43%)
         occurrences all number
    3
    4
    Syncope
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Tremor
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    3 / 16 (18.75%)
    0 / 14 (0.00%)
         occurrences all number
    5
    0
    Pyramidal tract syndrome
    Additional description: pyramidal tract dysfunction
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Eye disorders
    Blurred vision
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 14 (7.14%)
         occurrences all number
    1
    1
    Epiphora
    Additional description: Watery eye
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Eye pain
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Anorexia
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 14 (14.29%)
         occurrences all number
    6
    2
    Diarrhoea
         subjects affected / exposed
    4 / 16 (25.00%)
    3 / 14 (21.43%)
         occurrences all number
    6
    3
    Dry mouth
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal discomfort
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    3
    0
    Nausea
         subjects affected / exposed
    3 / 16 (18.75%)
    3 / 14 (21.43%)
         occurrences all number
    7
    5
    Vomiting
         subjects affected / exposed
    2 / 16 (12.50%)
    2 / 14 (14.29%)
         occurrences all number
    5
    2
    Abdominal pain
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    3
    0
    Constipation
         subjects affected / exposed
    0 / 16 (0.00%)
    4 / 14 (28.57%)
         occurrences all number
    0
    4
    Flatulence
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Mucositis oral
         subjects affected / exposed
    0 / 16 (0.00%)
    2 / 14 (14.29%)
         occurrences all number
    0
    2
    Gum bleeding
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Tooth pain
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 14 (7.14%)
         occurrences all number
    1
    2
    Skin hyperpigmentation
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 16 (6.25%)
    1 / 14 (7.14%)
         occurrences all number
    1
    1
    Rash
         subjects affected / exposed
    3 / 16 (18.75%)
    6 / 14 (42.86%)
         occurrences all number
    5
    6
    Urticaria
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Dry skin
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Cystitis
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Urinary incontinence
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Bladder pain
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Bone pain
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Joint pain
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Neck pain
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Muscle weakness
    Additional description: Lower extremity
         subjects affected / exposed
    1 / 16 (6.25%)
    2 / 14 (14.29%)
         occurrences all number
    1
    3
    Infections and infestations
    Infection
    Additional description: With normal ANC
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Urinary infection
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    1
    0
    Flu
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Furunculosis
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Tooth infection
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Hyperglycemia
         subjects affected / exposed
    4 / 16 (25.00%)
    2 / 14 (14.29%)
         occurrences all number
    14
    7
    Hyperkalemia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    2
    0
    Hypertriglyceridemia
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 14 (0.00%)
         occurrences all number
    4
    0
    Hyperuricemia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    10
    0
    Hypoalbuminaemia
         subjects affected / exposed
    4 / 16 (25.00%)
    1 / 14 (7.14%)
         occurrences all number
    11
    1
    Hypoglycaemia
         subjects affected / exposed
    1 / 16 (6.25%)
    0 / 14 (0.00%)
         occurrences all number
    4
    0
    Hypokalaemia
         subjects affected / exposed
    3 / 16 (18.75%)
    2 / 14 (14.29%)
         occurrences all number
    9
    2
    Hyponatraemia
         subjects affected / exposed
    2 / 16 (12.50%)
    0 / 14 (0.00%)
         occurrences all number
    4
    0
    Hypocalcaemia
         subjects affected / exposed
    0 / 16 (0.00%)
    1 / 14 (7.14%)
         occurrences all number
    0
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 May 2012
    Amendment includes: - Protocol amendment v2.0, - Revision of protocol title, - amendment of study design, primary- secondary objectives - revision of one inclusion criterion - increase in study duration - dose modification - revision of the response response criteria - amendment on study's statistical plan therefore reduce of sample size to 66 patients - add new study sites - change of principal investigator in approved site

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun Apr 28 22:29:13 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA