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    Clinical Trial Results:
    A Randomised Phase II study investigating pazopanib vs weekly paclitaxel in relapsed or progressive Transitional Cell Carcinoma (TCC) of the urothelium.

    Summary
    EudraCT number
    2011-001841-34
    Trial protocol
    GB  
    Global end of trial date
    06 Jul 2016

    Results information
    Results version number
    v1(current)
    This version publication date
    22 Jun 2018
    First version publication date
    22 Jun 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    PLUTO2011
    Additional study identifiers
    ISRCTN number
    ISRCTN73030316
    US NCT number
    -
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    NHS Greater Glasgow & Clyde
    Sponsor organisation address
    Gartnavel Royal Hospital, Glasgow, United Kingdom,
    Public contact
    Research & Development, NHS Greater Glasgow & Clyde, +44 01412111789, R&DIMP@ggc.scot.nhs.uk
    Scientific contact
    Research & Development, NHS Greater Glasgow & Clyde, +44 01412111789, R&DIMP@ggc.scot.nhs.uk
    Sponsor organisation name
    University of Glasgow
    Sponsor organisation address
    University Avenue, Glasgow, United Kingdom, G12 8QQ
    Public contact
    Ms Judith Dixon-Hughes, CRUK CTU Glasgow, 044 01413017540, judith.dixon@glasgow.ac.uk
    Scientific contact
    Professor Rob Jones, NHS Greater Glasgow and Clyde, r.jones@beatson.gla.ac.uk
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Sep 2016
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    06 Jul 2016
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Jul 2016
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to investigate whether pazopanib increases the overall survival time for patients with relapsed or progressive disease; in comparison to the current standard treatment, paclitaxel.
    Protection of trial subjects
    As part of the study patients required to attend for additional clinic visits and investigations which would be above those considered to be standard care. The visit schedule and the number and type of investigations were fully explained to patients verbally and in writing via the patient information sheet to ensure patients were fully aware what was in entailed in participating in the trial prior to them consenting to the study. The patient information sheet also fully explained the design of the study and that half of patients would receive paclitaxel and half would receive pazopanib. The side effects of both treatments were explained in patient information sheet, as where the expected side effects for them. All patients were closely monitored throughout the course of the study for adverse events and were advised to report adverse events to their study team as they arose.
    Background therapy
    -
    Evidence for comparator
    Although 2nd line chemotherapy is common practice in the UK and elsewhere, there is still no universally-accepted randomised controlled trial data to support the use of second-line chemotherapy rather than best supportive care alone and no international consensus on the optimal regimen. A survey of UK bladder cancer oncologists in 2009 showed that a wide variety of regimens were used in the 2nd line setting, none of which have supportive phase III data. Therefore, in order to better understand the likely benefits of pazopanib, a direct comparison of pazopanib and ‘standard of care’ is the ideal study to determine if pazopanib is worthy of further investigation in this setting. One suitable regimen is be weekly paclitaxel for up to 24 weeks. Unlike pazopanib, which can safely be given until disease progression or intolerance, paclitaxel may be associated with cumulative neurotoxicity, and so the total duration of therapy is limited in this study.
    Actual start date of recruitment
    01 Dec 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 131
    Worldwide total number of subjects
    131
    EEA total number of subjects
    131
    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)
    42
    From 65 to 84 years
    87
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    The study was opened to recruitment in August 2010 and closed to recruitment in October 2014. This study was opened to recruitment in the UK only and recruited 131 patients.

    Pre-assignment
    Screening details
    Consent for the study could be taken up to 8 weeks prior to date of randomisation. All other screening evaluations were performed within 28 days of study entry

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Arm A - Paclitaxel
    Arm description
    Patients will receive paclitaxel for up to 24 weeks. Infusions of paclitaxel 80mg/m2 will be administered on days 1, 8 and 25 of a 28 day cycle.
    Arm type
    Active comparator

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    80 mg/m2 day 1, 8, 15 of 28 day cycle for a maximum of 24 weeks

    Arm title
    Arm B - Pazopanib
    Arm description
    Patients will receive pazopanib 800mg PO once daily until progression
    Arm type
    Experimental

    Investigational medicinal product name
    Pazopanib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    800mg po daily until progression

    Number of subjects in period 1
    Arm A - Paclitaxel Arm B - Pazopanib
    Started
    65
    66
    Completed
    62
    63
    Not completed
    3
    3
         Consent withdrawn by subject
    3
    2
         Lost to follow-up
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Arm A - Paclitaxel
    Reporting group description
    Patients will receive paclitaxel for up to 24 weeks. Infusions of paclitaxel 80mg/m2 will be administered on days 1, 8 and 25 of a 28 day cycle.

    Reporting group title
    Arm B - Pazopanib
    Reporting group description
    Patients will receive pazopanib 800mg PO once daily until progression

    Reporting group values
    Arm A - Paclitaxel Arm B - Pazopanib Total
    Number of subjects
    65 66 131
    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
    Age (years)
    Units: years
        median (inter-quartile range (Q1-Q3))
    70 (63 to 77) 69 (61 to 75) -
    Gender categorical
    Units: Subjects
        Female
    16 22 38
        Male
    49 44 93
    Response to previous treatment
    Response to previous treatment (time to progression: ≤ 6 months v > 6 months)
    Units: Subjects
        <= 6 months
    49 48 97
        >6 months
    16 18 34
    Presence of visceral and/or bone metastasis
    Presence of visceral and/or bone metastasis (yes/ no)
    Units: Subjects
        Yes
    49 48 97
        No
    16 18 34
    Patient ECOG performance status
    Patient ECOG performance status (0, 1, 2)
    Units: Subjects
        ECOG 0
    25 26 51
        ECOG 1
    34 35 69
        ECOG 2
    6 5 11
    Subject analysis sets

    Subject analysis set title
    ITT
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    The intention-to-treat (ITT) population includes all patients randomised onto the study.

    Subject analysis sets values
    ITT
    Number of subjects
    131
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Age (years)
    Units: years
        median (inter-quartile range (Q1-Q3))
    69 (62 to 77)
    Gender categorical
    Units: Subjects
        Female
    38
        Male
    93
    Response to previous treatment
    Response to previous treatment (time to progression: ≤ 6 months v > 6 months)
    Units: Subjects
        <= 6 months
    97
        >6 months
    34
    Presence of visceral and/or bone metastasis
    Presence of visceral and/or bone metastasis (yes/ no)
    Units: Subjects
        Yes
    97
        No
    34
    Patient ECOG performance status
    Patient ECOG performance status (0, 1, 2)
    Units: Subjects
        ECOG 0
    51
        ECOG 1
    69
        ECOG 2
    11

    End points

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    End points reporting groups
    Reporting group title
    Arm A - Paclitaxel
    Reporting group description
    Patients will receive paclitaxel for up to 24 weeks. Infusions of paclitaxel 80mg/m2 will be administered on days 1, 8 and 25 of a 28 day cycle.

    Reporting group title
    Arm B - Pazopanib
    Reporting group description
    Patients will receive pazopanib 800mg PO once daily until progression

    Subject analysis set title
    ITT
    Subject analysis set type
    Intention-to-treat
    Subject analysis set description
    The intention-to-treat (ITT) population includes all patients randomised onto the study.

    Primary: Primary end point - Overall survival

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    End point title
    Primary end point - Overall survival
    End point description
    End point type
    Primary
    End point timeframe
    Overall survival is defined as the time from the date of randomisation to the date of death from any cause. Patients who do not die will be censored at the date they were last known to be alive.
    End point values
    Arm A - Paclitaxel Arm B - Pazopanib ITT
    Number of subjects analysed
    65
    66
    131
    Units: Months
        median (confidence interval 80%)
    8 (6.9 to 9.7)
    4.7 (4.2 to 6.4)
    6.7 (5.4 to 7.3)
    Statistical analysis title
    Cox regression model
    Statistical analysis description
    The primary overall survival comparison was made using the estimated hazard ratio and p-values from a Cox regression model incorporating terms for the minimisation stratification factors and study arm.
    Comparison groups
    Arm A - Paclitaxel v Arm B - Pazopanib
    Number of subjects included in analysis
    131
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    P-value
    = 0.89 [1]
    Method
    Regression, Cox
    Parameter type
    Hazard ratio (HR)
    Point estimate
    1.28
    Confidence interval
         level
    80%
         sides
    2-sided
         lower limit
    0.99
         upper limit
    1.67
    Notes
    [1] - 1-sided

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were recorded from start of treatment and throughout the study period and for at least 30 days after discontinuation of study medication. All adverse events were followed until resolution.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    CTCAE
    Dictionary version
    4
    Reporting groups
    Reporting group title
    Arm A - Paclitaxel
    Reporting group description
    -

    Reporting group title
    Arm B - Pazopanib
    Reporting group description
    -

    Serious adverse events
    Arm A - Paclitaxel Arm B - Pazopanib
    Total subjects affected by serious adverse events
         subjects affected / exposed
    33 / 64 (51.56%)
    42 / 65 (64.62%)
         number of deaths (all causes)
    56
    59
         number of deaths resulting from adverse events
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thromboembolic event
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Surgical and medical procedures - Other, specify
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         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
    Chills
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Death NOS
         subjects affected / exposed
    0 / 64 (0.00%)
    2 / 65 (3.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 2
    Oedema limbs
         subjects affected / exposed
    1 / 64 (1.56%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 64 (0.00%)
    3 / 65 (4.62%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fever
         subjects affected / exposed
    5 / 64 (7.81%)
    4 / 65 (6.15%)
         occurrences causally related to treatment / all
    2 / 6
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gait disturbance
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 64 (1.56%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 64 (0.00%)
    4 / 65 (6.15%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusion
         subjects affected / exposed
    1 / 64 (1.56%)
    2 / 65 (3.08%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Testicular disorder
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Testicular pain
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal haemorrhage
         subjects affected / exposed
    0 / 64 (0.00%)
    2 / 65 (3.08%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal obstruction
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 64 (0.00%)
    6 / 65 (9.23%)
         occurrences causally related to treatment / all
    0 / 0
    6 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alkaline phosphatase increased
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 64 (0.00%)
    3 / 65 (4.62%)
         occurrences causally related to treatment / all
    0 / 0
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Creatinine increased
         subjects affected / exposed
    0 / 64 (0.00%)
    3 / 65 (4.62%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutrophil count decreased
         subjects affected / exposed
    2 / 64 (3.13%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urine output decreased
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial flutter
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (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
    Anaemia
         subjects affected / exposed
    2 / 64 (3.13%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 64 (3.13%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    6 / 64 (9.38%)
    5 / 65 (7.69%)
         occurrences causally related to treatment / all
    3 / 7
    1 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hoarseness
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    3 / 64 (4.69%)
    2 / 65 (3.08%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders - Other, specify
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cognitive disturbance
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depressed level of consciousness
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dizziness
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    1 / 64 (1.56%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral sensory neuropathy
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stroke
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tremor
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 64 (1.56%)
    6 / 65 (9.23%)
         occurrences causally related to treatment / all
    0 / 1
    2 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    2 / 64 (3.13%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colonic obstruction
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colonic perforation
         subjects affected / exposed
    1 / 64 (1.56%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Constipation
         subjects affected / exposed
    0 / 64 (0.00%)
    3 / 65 (4.62%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 64 (1.56%)
    4 / 65 (6.15%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mucositis oral
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    2 / 64 (3.13%)
    5 / 65 (7.69%)
         occurrences causally related to treatment / all
    3 / 3
    4 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal fistula
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal pain
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    3 / 64 (4.69%)
    5 / 65 (7.69%)
         occurrences causally related to treatment / all
    3 / 4
    2 / 6
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 64 (3.13%)
    2 / 65 (3.08%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Chronic kidney disease
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematuria
         subjects affected / exposed
    3 / 64 (4.69%)
    3 / 65 (4.62%)
         occurrences causally related to treatment / all
    0 / 3
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Proteinuria
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renam and urinary disorders - Other, specify
         subjects affected / exposed
    1 / 64 (1.56%)
    4 / 65 (6.15%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary fistula
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary incontinence
         subjects affected / exposed
    1 / 64 (1.56%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract obstruction
         subjects affected / exposed
    2 / 64 (3.13%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Photosensitivity
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rash maculo-papular
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 64 (0.00%)
    2 / 65 (3.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest wall pain
         subjects affected / exposed
    0 / 64 (0.00%)
    2 / 65 (3.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle weakness left-sided
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Muscle weakness upper limb
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neck pain
         subjects affected / exposed
    0 / 64 (0.00%)
    2 / 65 (3.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    2 / 64 (3.13%)
    2 / 65 (3.08%)
         occurrences causally related to treatment / all
    0 / 2
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    2 / 64 (3.13%)
    4 / 65 (6.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    0 / 64 (0.00%)
    2 / 65 (3.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 64 (1.56%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bladder infection
         subjects affected / exposed
    0 / 64 (0.00%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial infection
         subjects affected / exposed
    1 / 64 (1.56%)
    0 / 65 (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 - Other, specify
         subjects affected / exposed
    5 / 64 (7.81%)
    4 / 65 (6.15%)
         occurrences causally related to treatment / all
    5 / 8
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Lung infection
         subjects affected / exposed
    5 / 64 (7.81%)
    2 / 65 (3.08%)
         occurrences causally related to treatment / all
    2 / 5
    1 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 64 (1.56%)
    1 / 65 (1.54%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    6 / 64 (9.38%)
    4 / 65 (6.15%)
         occurrences causally related to treatment / all
    2 / 6
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Arm A - Paclitaxel Arm B - Pazopanib
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    57 / 64 (89.06%)
    62 / 65 (95.38%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    5 / 64 (7.81%)
    16 / 65 (24.62%)
         occurrences all number
    15
    38
    Hypotension
         subjects affected / exposed
    4 / 64 (6.25%)
    0 / 65 (0.00%)
         occurrences all number
    7
    0
    Thromboembolic event
         subjects affected / exposed
    4 / 64 (6.25%)
    0 / 65 (0.00%)
         occurrences all number
    7
    0
    Immune system disorders
    Allergic reaction
         subjects affected / exposed
    5 / 64 (7.81%)
    0 / 65 (0.00%)
         occurrences all number
    6
    0
    General disorders and administration site conditions
    Oedema limbs
         subjects affected / exposed
    8 / 64 (12.50%)
    5 / 65 (7.69%)
         occurrences all number
    18
    10
    General disorders and administration site conditions - Other, specify
         subjects affected / exposed
    12 / 64 (18.75%)
    9 / 65 (13.85%)
         occurrences all number
    37
    18
    Pain
         subjects affected / exposed
    21 / 64 (32.81%)
    20 / 65 (30.77%)
         occurrences all number
    59
    56
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    5 / 64 (7.81%)
    4 / 65 (6.15%)
         occurrences all number
    11
    12
    Investigations
    Weight loss
         subjects affected / exposed
    0 / 64 (0.00%)
    4 / 65 (6.15%)
         occurrences all number
    0
    7
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 64 (6.25%)
    0 / 65 (0.00%)
         occurrences all number
    7
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    14 / 64 (21.88%)
    5 / 65 (7.69%)
         occurrences all number
    29
    12
    Dyspnoea
         subjects affected / exposed
    14 / 64 (21.88%)
    10 / 65 (15.38%)
         occurrences all number
    27
    30
    Epistaxis
         subjects affected / exposed
    5 / 64 (7.81%)
    0 / 65 (0.00%)
         occurrences all number
    6
    0
    Hoarseness
         subjects affected / exposed
    0 / 64 (0.00%)
    4 / 65 (6.15%)
         occurrences all number
    0
    23
    Respiratory, thoracic and mediastinal disorders - Other, specify
         subjects affected / exposed
    9 / 64 (14.06%)
    0 / 65 (0.00%)
         occurrences all number
    11
    0
    Voice alteration
         subjects affected / exposed
    0 / 64 (0.00%)
    6 / 65 (9.23%)
         occurrences all number
    0
    17
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 64 (0.00%)
    5 / 65 (7.69%)
         occurrences all number
    0
    12
    Dysgeusia
         subjects affected / exposed
    4 / 64 (6.25%)
    9 / 65 (13.85%)
         occurrences all number
    9
    26
    Headache
         subjects affected / exposed
    0 / 64 (0.00%)
    4 / 65 (6.15%)
         occurrences all number
    0
    10
    Peripheral motor neuropathy
         subjects affected / exposed
    13 / 64 (20.31%)
    0 / 65 (0.00%)
         occurrences all number
    24
    0
    Peripheral sensory neuropathy
         subjects affected / exposed
    28 / 64 (43.75%)
    4 / 65 (6.15%)
         occurrences all number
    122
    6
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    12 / 64 (18.75%)
    8 / 65 (12.31%)
         occurrences all number
    20
    14
    Constipation
         subjects affected / exposed
    16 / 64 (25.00%)
    14 / 65 (21.54%)
         occurrences all number
    43
    36
    Diarrhoea
         subjects affected / exposed
    18 / 64 (28.13%)
    32 / 65 (49.23%)
         occurrences all number
    39
    76
    Dry mouth
         subjects affected / exposed
    4 / 64 (6.25%)
    0 / 65 (0.00%)
         occurrences all number
    5
    0
    Dyspepsia
         subjects affected / exposed
    6 / 64 (9.38%)
    5 / 65 (7.69%)
         occurrences all number
    11
    10
    Gastrointestinal disorders - Other, specify
         subjects affected / exposed
    6 / 64 (9.38%)
    0 / 65 (0.00%)
         occurrences all number
    18
    0
    Mucositis oral
         subjects affected / exposed
    14 / 64 (21.88%)
    11 / 65 (16.92%)
         occurrences all number
    26
    24
    Nausea
         subjects affected / exposed
    30 / 64 (46.88%)
    31 / 65 (47.69%)
         occurrences all number
    70
    81
    Vomiting
         subjects affected / exposed
    17 / 64 (26.56%)
    20 / 65 (30.77%)
         occurrences all number
    20
    39
    Fatigue
         subjects affected / exposed
    48 / 64 (75.00%)
    49 / 65 (75.38%)
         occurrences all number
    190
    184
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    6 / 64 (9.38%)
    6 / 65 (9.23%)
         occurrences all number
    10
    9
    Renal and urinary disorders - Other, specify
         subjects affected / exposed
    6 / 64 (9.38%)
    9 / 65 (13.85%)
         occurrences all number
    14
    14
    Urinary frequency
         subjects affected / exposed
    4 / 64 (6.25%)
    0 / 65 (0.00%)
         occurrences all number
    5
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    28 / 64 (43.75%)
    0 / 65 (0.00%)
         occurrences all number
    95
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 64 (0.00%)
    8 / 65 (12.31%)
         occurrences all number
    0
    18
    Skin and subcutaneous tissue disorders - Other, specify
         subjects affected / exposed
    13 / 64 (20.31%)
    6 / 65 (9.23%)
         occurrences all number
    30
    27
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    8 / 64 (12.50%)
    9 / 65 (13.85%)
         occurrences all number
    16
    19
    Musculoskeletal and connective tissue disorder - Other, specify
         subjects affected / exposed
    5 / 64 (7.81%)
    0 / 65 (0.00%)
         occurrences all number
    5
    0
    Myalgia
         subjects affected / exposed
    11 / 64 (17.19%)
    5 / 65 (7.69%)
         occurrences all number
    23
    7
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    15 / 64 (23.44%)
    23 / 65 (35.38%)
         occurrences all number
    22
    63
    Infections and infestations
    Infections and infestations - Other, specify
         subjects affected / exposed
    8 / 64 (12.50%)
    6 / 65 (9.23%)
         occurrences all number
    9
    18
    Urinary tract infection
         subjects affected / exposed
    9 / 64 (14.06%)
    7 / 65 (10.77%)
         occurrences all number
    13
    11

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    09 Jan 2012
    Amendment to ethics after notice of non acceptance from MHRA - This made it clear that after 2 weeks of no treatment that patient should be withdrawn from study treatment, it also amended the QTc prolongation management section
    25 Apr 2013
    This amendment allowed for a single additional liver function test for pazopanib patients. This reflected revised safety advice issued by the manufacturer. The eligibility criteria and dose modification criteria regarding liver function abnormalities have also been amended in line with this new advice. The eligibility criteria was also broadened to include patients with ECOG performance status 2. Also a negative urinalysis dipstick test has also been added as sufficient evidence of the absence of proteinuria.
    04 Aug 2014
    A restriction on the concomitant use of strong CYP3A4 inhibitors for patients receiving pazopanib was added in line with emerging data supplied by the manufacturer
    22 Oct 2014
    This amendment was to advise of a termporay halt to the trial on the advise of the IDMC

    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
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