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   43881   clinical trials with a EudraCT protocol, of which   7295   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:
    Phase II single-arm study of first line treatment with gemcitabine and pazopanib in patients with inoperable locally advanced or metastatic biliary tree cancer (cholangiocarcinoma or gallbladder carcinoma)

    Summary
    EudraCT number
    2012-001705-24
    Trial protocol
    GR  
    Global end of trial date
    28 Sep 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    08 Nov 2019
    First version publication date
    08 Nov 2019
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    HE37/12
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01855724
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Hellenic Cooperative Oncology Group
    Sponsor organisation address
    M. Hatzikostanti 18, Athens, Greece, 11524
    Public contact
    Clinical Trials, Hellenic Cooperative Oncology Group, 0030 2106912520, hecogoff@otenet.gr
    Scientific contact
    Clinical Trials, Hellenic Cooperative Oncology Group, 0030 2106912520, 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
    23 Jul 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Sep 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To assess the efficacy of pazopanib combination with gemcitabine (measured as Objective Response Rate) in patients with inoperable locally advanced or metastatic biliary tree carcinoma.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles of the Declaration of Helsinki, the Good Clinical Practice guidelines and the local regulatory requirements.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    15 Apr 2013
    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: 29
    Worldwide total number of subjects
    29
    EEA total number of subjects
    29
    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)
    10
    From 65 to 84 years
    18
    85 years and over
    1

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Participants were enrolled in the study from 28 June 2013 until 15 March 2018 from 10 sites in Greece.

    Pre-assignment
    Screening details
    Patients were screened for eligibility before entering the study and signed the informed consent form which was obtained before any study procedure.

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

    Arms
    Arm title
    Gemcitabine - Pazopanib
    Arm description
    Gemcitabine (1000mg/m2, D1 & 8) - Pazopanib (800mg daily dose) treatment combination was administered in treatment cycles, of 21 day duration per cycle. In the absence of disease progression or significant toxicity, 8 cycles of combination treatment were administered, followed by Pazopanib monotherapy at an 800 mg daily dose. Following 8 cycles of Gemcitabine – Pazopanib treatment, patients continued with Pazopanib monotherapy. Each monotherapy cycle had duration of 21 days. Patients received 800mg Pazopanib orally on a daily basis until disease progression or toxicity that was treated and significantly affected their QoL
    Arm type
    Experimental

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Cytotoxic agent Gemcitabine, was administered at an 1000 mg/m2 dose diluted in 250 ml of N/S, in a 30-minute intravenous infusion on days 1 and 8, every 21 days, for 8 cycles.

    Investigational medicinal product name
    Pazopanib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Pazopanib was administered at the dose of 800mg on daily basis for 8 cycles of 21 days duration. In the absence of disease progression or significant toxicity Pazopanib was administered as maintenance treatment (monotherapy) at an 800mg daily dose.

    Number of subjects in period 1
    Gemcitabine - Pazopanib
    Started
    29
    Completed
    11
    Not completed
    18
         Physician decision
    1
         Consent withdrawn by subject
    2
         Disease progression
    7
         Adverse event, non-fatal
    6
         Death
    1
         Temporary suspension of the trial
    1

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall Trial
    Reporting group description
    -

    Reporting group values
    Overall Trial Total
    Number of subjects
    29 29
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    10 10
        From 65-84 years
    18 18
        85 years and over
    1 1
    Age continuous
    Units: years
        median (full range (min-max))
    68.6 (46.5 to 85.0) -
    Gender categorical
    Units: Subjects
        Female
    14 14
        Male
    15 15
    Subject analysis sets

    Subject analysis set title
    Per Protocol Population
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Patients who received at least one full study medication cycle, had an initial disease evaluation and the right histological type of cancer.

    Subject analysis sets values
    Per Protocol Population
    Number of subjects
    21
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    7
        From 65-84 years
    13
        85 years and over
    1
    Age continuous
    Units: years
        median (full range (min-max))
    68.6 (46.5 to 85.0)
    Gender categorical
    Units: Subjects
        Female
    11
        Male
    10

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Gemcitabine - Pazopanib
    Reporting group description
    Gemcitabine (1000mg/m2, D1 & 8) - Pazopanib (800mg daily dose) treatment combination was administered in treatment cycles, of 21 day duration per cycle. In the absence of disease progression or significant toxicity, 8 cycles of combination treatment were administered, followed by Pazopanib monotherapy at an 800 mg daily dose. Following 8 cycles of Gemcitabine – Pazopanib treatment, patients continued with Pazopanib monotherapy. Each monotherapy cycle had duration of 21 days. Patients received 800mg Pazopanib orally on a daily basis until disease progression or toxicity that was treated and significantly affected their QoL

    Subject analysis set title
    Per Protocol Population
    Subject analysis set type
    Per protocol
    Subject analysis set description
    Patients who received at least one full study medication cycle, had an initial disease evaluation and the right histological type of cancer.

    Primary: Objective response Rate

    Close Top of page
    End point title
    Objective response Rate [1]
    End point description
    Objective response rate was defined as the percentage of patients with a confirmed complete (CR) or partial response (PR) as per RECIST 1.1 criteria.
    End point type
    Primary
    End point timeframe
    Imaging evaluation for the determination of tumor response was performed every 8 weeks.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The objective response rate, i.e. the percentage of patients achieving a complete or partial response as the best response was described using descriptive statistics for the ITT and the PP population
    End point values
    Gemcitabine - Pazopanib Per Protocol Population
    Number of subjects analysed
    29
    21
    Units: percentage of patients with CR/PR
        Objective response rate (%)
    14
    19
    No statistical analyses for this end point

    Secondary: Progression Free Survival

    Close Top of page
    End point title
    Progression Free Survival
    End point description
    Progression Free Survival was calculated from the date of patient's entry into the study until the first documented disease progression, death or last contact, whichever occurred first.
    End point type
    Secondary
    End point timeframe
    Patients were followed up for a median of 25.8 months (95% CI 13.5-25.8).
    End point values
    Gemcitabine - Pazopanib
    Number of subjects analysed
    29
    Units: months
        median (confidence interval 95%)
    6.3 (2.3 to 8.0)
    No statistical analyses for this end point

    Secondary: Overall Survival

    Close Top of page
    End point title
    Overall Survival
    End point description
    Overall Survival was calculated from the date of patient's entry into the study until death or last contact.
    End point type
    Secondary
    End point timeframe
    Patients were followed up for a median of 25.8 months (95% CI 13.5-25.8).
    End point values
    Gemcitabine - Pazopanib
    Number of subjects analysed
    29
    Units: months
        median (confidence interval 95%)
    10.4 (7.3 to 13.4)
    No statistical analyses for this end point

    Secondary: Safety

    Close Top of page
    End point title
    Safety
    End point description
    Safety was assessed in the safety population consisting of all patients that received at least one dose of the study drug (s).
    End point type
    Secondary
    End point timeframe
    Evaluation of Adverse Events (AEs) was performed every 21 days (per treatment cycle) throughout the course of treatment.
    End point values
    Gemcitabine - Pazopanib
    Number of subjects analysed
    29
    Units: number of patients
        Any adverse event
    29
        Fatal adverse event
    1
        Serious adverse event
    13
    No statistical analyses for this end point

    Secondary: Quality of Life

    Close Top of page
    End point title
    Quality of Life
    End point description
    The Quality of Life (QoL) was assessed using the EUROQOL 5D questionnaire that consists of 5 dimensions including mobility, self-care, usual activities, pain/discomfort and anxiety/depression and the EQ-VAS measuring the patient's health status in a scale of 0 to 100 with 0 indicating the worst health and 100 corresponding to the best health, as rated by the patient.
    End point type
    Secondary
    End point timeframe
    The EUROQOL 5D Questionnaire was completed before treatment initiation, every 8 weeks and post treatment.
    End point values
    Gemcitabine - Pazopanib
    Number of subjects analysed
    28 [2]
    Units: EQ-VAS
    arithmetic mean (standard deviation)
        Baseline
    55 ( 31.3 )
        Last treatment cycle
    54.1 ( 30.2 )
    Notes
    [2] - 28 patients completed the EQ-5D questionnaire at baseline and 23 at their last cycle of treatment.
    No statistical analyses for this end point

    Secondary: 6-month Progression Free Survival Rate

    Close Top of page
    End point title
    6-month Progression Free Survival Rate
    End point description
    The percentage of patients surviving 6 months post study entry.
    End point type
    Secondary
    End point timeframe
    Patients were followed up for a median of 25.8 months (95% CI 13.5-25.8).
    End point values
    Gemcitabine - Pazopanib
    Number of subjects analysed
    29
    Units: percentage of patients
    52
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Upon signature of the ICF up to 30 days after the last administration of Pazopanib. Following the 30 day EOT visit all ongoing SAEs as well as ongoing related AEs and new related SAEs were collected and followed till resolution/stabilisation/new treatment
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    20.1
    Reporting groups
    Reporting group title
    Gemcitabine - Pazopanib
    Reporting group description
    The combination was administered as follows: Gemcitabine 1000mg/m2 i.v on days 1 and 8 with Pazopanib 800mg daily dose per os on days 1-21, every 21 days for 8 cycles followed by Pazopanib monotherapy 800mg daily dose per os in days 1-21 every 21 days until disease progression was occurred or unacceptable toxicity.

    Serious adverse events
    Gemcitabine - Pazopanib
    Total subjects affected by serious adverse events
         subjects affected / exposed
    13 / 29 (44.83%)
         number of deaths (all causes)
    25
         number of deaths resulting from adverse events
    1
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 29 (10.34%)
         occurrences causally related to treatment / all
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 29 (10.34%)
         occurrences causally related to treatment / all
    2 / 3
         deaths causally related to treatment / all
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Alkaline Phosphatase increased
    Additional description: increased level of alkaline phosphatase in a blood specimen
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood bilirubin increased
         subjects affected / exposed
    3 / 29 (10.34%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Ileus
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    jejunal hemorrhage
    Additional description: Bleeding from the jejunal wall.
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Lung abscess
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cholecystitis
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    hepatic coma
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Lung infection
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic infection
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    Gemcitabine - Pazopanib
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    28 / 29 (96.55%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    15 / 29 (51.72%)
         occurrences all number
    32
    General disorders and administration site conditions
    edema face
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    edema limbs
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    4 / 29 (13.79%)
         occurrences all number
    5
    Fatigue
         subjects affected / exposed
    16 / 29 (55.17%)
         occurrences all number
    21
    fever
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    3 / 29 (10.34%)
         occurrences all number
    6
    other - voice disorders
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Pain
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Rhinitis allergic
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Cough
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Dyspnoea
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2
    Epistaxis
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    other - pharyngolaryngeal pain
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2
    other - distress
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Investigations
    White blood cell count decreased
         subjects affected / exposed
    24 / 29 (82.76%)
         occurrences all number
    79
    Neutrophil count decreased
         subjects affected / exposed
    24 / 29 (82.76%)
         occurrences all number
    71
    Alanine aminotransferase increased
         subjects affected / exposed
    15 / 29 (51.72%)
         occurrences all number
    32
    alkaline phosphatase increased
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    8 / 29 (27.59%)
         occurrences all number
    11
    Aspartate aminotransferase increased
         subjects affected / exposed
    13 / 29 (44.83%)
         occurrences all number
    22
    Blood bilirubin increased
         subjects affected / exposed
    8 / 29 (27.59%)
         occurrences all number
    13
    cholesterol high
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    3 / 29 (10.34%)
         occurrences all number
    5
    creatinine increased
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    3 / 29 (10.34%)
         occurrences all number
    3
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    8 / 29 (27.59%)
         occurrences all number
    10
    other - lactate dehydrogenase serum increased
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Lymphocyte count decreased
         subjects affected / exposed
    4 / 29 (13.79%)
         occurrences all number
    11
    Platelet count decreased
         subjects affected / exposed
    12 / 29 (41.38%)
         occurrences all number
    30
    Amylase increased
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    2
    Sinus tachycardia
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    3
    Dysgeusia
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    3
    Sleep disorder
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Neuropathy peripheral
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    12 / 29 (41.38%)
         occurrences all number
    17
    Eye disorders
    other - eyelash oedema
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    2
    watering eye
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    7 / 29 (24.14%)
         occurrences all number
    12
    Ascites
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Constipation
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2
    Diarrhoea
         subjects affected / exposed
    8 / 29 (27.59%)
         occurrences all number
    14
    Dyspepsia
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Oesophageal haemorrhage
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Reflux gastritis
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2
    Haematochezia
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    other - epigastric pain
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    other - mucosal defecation
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Stomatitis
         subjects affected / exposed
    3 / 29 (10.34%)
         occurrences all number
    3
    Nausea
         subjects affected / exposed
    8 / 29 (27.59%)
         occurrences all number
    13
    Periodontal disease
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Vomiting
         subjects affected / exposed
    7 / 29 (24.14%)
         occurrences all number
    9
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Dry skin
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Acne
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Hair colour changes
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2
    Skin hyperpigmentation
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Proteinuria
         subjects affected / exposed
    6 / 29 (20.69%)
         occurrences all number
    8
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Back pain
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Chest pain
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Pain in extremity
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Infections and infestations
    Cholangitis
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Papulopustular rash
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Skin infection
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Tooth infection
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2
    Urinary tract infection
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2
    Metabolism and nutrition disorders
    other - anorexia
    alternative dictionary used: CTCAE 4.03
         subjects affected / exposed
    4 / 29 (13.79%)
         occurrences all number
    5
    Hyperglycaemia
         subjects affected / exposed
    6 / 29 (20.69%)
         occurrences all number
    16
    Hyperkalaemia
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2
    Hypermagnesaemia
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Hypernatraemia
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Hypertriglyceridaemia
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2
    Hypoalbuminaemia
         subjects affected / exposed
    5 / 29 (17.24%)
         occurrences all number
    7
    Hypocalcaemia
         subjects affected / exposed
    4 / 29 (13.79%)
         occurrences all number
    6
    Hypoglycaemia
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    1
    Hypokalaemia
         subjects affected / exposed
    4 / 29 (13.79%)
         occurrences all number
    7
    Hypomagnesaemia
         subjects affected / exposed
    1 / 29 (3.45%)
         occurrences all number
    4
    Hyponatraemia
         subjects affected / exposed
    6 / 29 (20.69%)
         occurrences all number
    7
    Hypophosphataemia
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2
    Hyperphosphataemia
         subjects affected / exposed
    2 / 29 (6.90%)
         occurrences all number
    2

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Sep 2017
    Amendment of the inclusion criteria 3 and 6: Criterion 3: Histologic or cytologic diagnosis of cholangiocarcinoma (intrahepatic or extrahepatic biliary adenocarcinoma, gallbladder adenocarcinoma and periampullary bile duct adenocarcinoma). Criterion 6: No previous administration of other chemotherapy or targeted therapy. By exception, patients with primary lesion that was removed in the past and received adjuvant chemotherapy with gemcitabine, with the last dose being administered at least 1 year prior the patient’s inclusion date in this protocol, are acceptable. Pages 23-25: Pazopanib (Votrient®) available for the study from its initiation onwards is available in white 200mg tablets (34 in each bottle) compared to the pink, commercially available, tablets. The stock for this IMP expires in November 2017 and will be used to cover the needs of the study patients until stock-out and as per its expiry date. Then, pazopanib (Votrient®) supplied in the study, will be the 200mg commercially available product (pink tablets, 90 in each bottle), in its commercial packaging with appropriate labelling for use in the clinical trial. Packaging and labelling of the commercially available medicinal product to be used in the clinical trial will be performed by Novartis as per GMP, ICH/GCP and local law requirements. Labels will include the necessary information in Greek, will comply with applicable legislation and will not provide any patient information. Pazopanib will be dispensed to patients for home use at each study visit from the study physician/designated site personnel. Each package will contain sufficient drug supply until the patient’s next visit. Study drug will be received by a delegated person at the study site, handled and stored safely and properly, and kept in a secured location to which only the investigator and delegated site personnel have access. Upon receipt, pazopanib should be stored according to the instructions on the drug label.

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    22 Jul 2013
    For safety reasons, upon a request from Glaxo Smith Kline, in clinical studies investigating the combination of Gemcitabine – Pazopanib the enrollment was suspended.
    05 May 2014

    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 © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA