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   43873   clinical trials with a EudraCT protocol, of which   7292   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:
    PAZOFOS: A Phase Ib and Randomised Phase II Trial of Pazopanib with or without Fosbretabulin in Advanced Recurrent Ovarian Cancer

    Summary
    EudraCT number
    		 2013-005471-40
    Trial protocol
    		 GB  
    Global end of trial date
    05 Dec 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Jun 2023
    First version publication date
    28 Jun 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CFTSp074
    Additional study identifiers
    ISRCTN number
    		 ISRCTN30090285
    US NCT number
    		 NCT02055690
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    The Christie NHS Foundation Trust
    Sponsor organisation address
    Wilmslow Road, Manchester, United Kingdom, M20 4BX
    Public contact
    Clinical Trials Project Manager, The Christie NHS Foundation Trust, +44 0161 918 7492, colin.lunt@christie.nhs.uk
    Scientific contact
    Clinical Trials Project Manager, The Christie NHS Foundation Trust, +44 0161 918 7492, colin.lunt@christie.nhs.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
    18 Jul 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    24 Nov 2017
    Global end of trial reached?
    Yes
    Global end of trial date
    05 Dec 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    Phase Ib (dose escalation) objectives (a) To propose a recommended dose for Phase II evaluation by: Establishing the maximum tolerated dose of Fosbretabulin in combination with Pazopanib. (b) Assessing the safety and toxicity profile of Fosbretabulin in combination with Pazopanib. Randomised Phase II objectives To determine whether combining Fosbretabulin with pazopanib produces a significant improvement in progression free survival compared to Pazopanib alone.
    Protection of trial subjects
    The Sponsor or Investigator may take appropriate urgent safety measures (USMs) in order to protect the patient of a clinical trial against any immediate hazard to their health or safety without prior authorisation from the MHRA and ethics committee. This includes procedures taken to protect patients from pandemics or infections that pose serious risk to human health. USMs may be taken without prior authorisation from the competent authority or sponsor. Should the site initiate a USM, the Investigator must inform the MAHSC-CTU immediately. The notification should include the date of the USM, who took the decision and why the action was taken. The MAHSC-CTU will then notify the Sponsor, MHRA and the REC within three days of USM initiation. Examples of issues requiring urgent safety measures include: - A single report of a SAR with an unexpected outcome (e.g. death) - An increase in rate of occurrence of SAR which is judged to be clinically important - A post-trial SUSAR occurring after the subject has left the trial - A new event relating to the use or development of an IMP likely to affect the safety of subjects e.g. an SAE that could be associated with the procedures and which could lead to modification of the trial conduct; lack of efficacy of an IMP used for a life-threatening disease; a major safety finding from a newly completed animal study A protocol amendment is formally submitted within 3 days by the CI and CTPM to the relevant bodies in conjunction with the sponsor. Annual progress reports will be submitted to the REC. A Development Safety Update Report (DSUR) is submitted annually to the MHRA and REC in accordance with requirements.
    Background therapy
    		 All patients will receive oral metoclopramide 20 mg and paracetamol 1 g 30 minutes prior to administration of fosbretabulin, with dexamethasone 4 mg added if there is > grade 1 fatigue and nausea following the first infusion. Metoclopramide may be substituted by an alternative if necessary on the grounds of unsuitability for a patient. Note that ondansetron, granisetron and related drugs impact of the QTc.
    Evidence for comparator
    		 Fosbretabulin is a synthetic phosphorylated prodrug of combretastatin A4, a naturally occurring derivative of the South African tree Combretum caffrum and a potent inhibitor of microtubule assembly. Evidence of its vascular disrupting activity was first obtained in rodent cancer models and then subsequently established in solid tumors in humans. Combretastatin A4 phosphate targets pre-existing tumor neovasculature, resulting in an acute, reversible reduction in tumor blood flow, leading to central necrosis within tumors. Although VDAs, such as fosbretabulin, have been shown to rapidly reduce blood flow to tumors, they have limited activity as single agents due to rapid regrowth of tumors. This is thought to be due to circulating endothelial progenitor cells repopulating the rim of tumor; kept viable due to surrounding normal vessels. VEGF inhibition has been shown to prevent circulating endothelial progenitor recruitment, and combining VEGF inhibitors with VDAs has in vivo additive anti-tumor activity.
    Actual start date of recruitment
    21 Jul 2014
    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: 33
    Worldwide total number of subjects
    33
    EEA total number of subjects
    0
    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)
    19
    From 65 to 84 years
    14
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Eligible patients were females age 18 or over, and had recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma. All eligible patients had received ≥1 prior lines of platinum chemotherapy, had progressive evaluable disease according to RECIST v1.1 and/or GCIG CA-125 criteria and an ECOG performance status of 0-1

    Pre-assignment
    Screening details
    		 Screening consisted of an assessment of medical history and the following examinations to assess eligibility: Scan of abdomen and pelvis to allow for RECIST 1.1 assessment; ECG with QTc evaluation; Who performance status; safety laboratory assessments including haematology,clinical chemistry; pregnancy test; Translational research samples

    Period 1
    Period 1 title
    Phase II (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded
    Blinding implementation details
    Because of the route of administration of fosbretabulin, the trial and therefore randomisation will not be blinded.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Pazopanib and fosbretabulin
    Arm description
    		 Pazopanib 600 mg once daily and fosbretabulin 54 mg/m2 on days 1, 8, 15, every 28 days
    Arm type
    		 Experimental

    Investigational medicinal product name
    Pazopanib
    Investigational medicinal product code
    Other name
    Votrient
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    600 mg pazopanib administered orally (tablets) without food (≥1 h before or ≥ 2 h after a meal) once daily, every 28 days.

    Investigational medicinal product name
    Fosbretabulin
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Fosbretabulin 54 mg/m2 was administered via a peripheral vein as a weekly intravenous infusion (10-min infusion time) on days 1, 8, 15, every 28 days, for a maximum of 6 cycles. The weekly dose of fosbretabulin was calculated according to body surface area (BSA) and capped at a BSA of 2.2m^2. When pazopanib and fosbretabulin were administered together pazopanib was administered ≥1 h prior to fosbretabulin.

    Arm title
    		 Single-agent pazopanib
    Arm description
    		 Pazopanib 800 mg once daily, every 28 days
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Pazopanib
    Investigational medicinal product code
    Other name
    Votrient
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    800 mg pazopanib administered orally (tablets) without food (≥1 h before or ≥ 2 h after a meal) once daily, every 28 days.

    Number of subjects in period 1 [1]
    		Pazopanib and fosbretabulin Single-agent pazopanib
    Started
    11
    10
    Completed
    11
    10
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Pazofos consisted of both a phase 1b and a Phase II trial. The initial phase 1b dose finding non-randomised phase recruited 12 patients. This subset of data has been included as a subject analysis set in order to record baseline and endpoint results. The remaining 21 patients were recruited to the randomised phase II trial where they received either pazopanib 600mg OD and fosbretabulin, or 800mg OD pazopanib alone.

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Pazopanib and fosbretabulin
    Reporting group description
    		 Pazopanib 600 mg once daily and fosbretabulin 54 mg/m2 on days 1, 8, 15, every 28 days

    Reporting group title
    Single-agent pazopanib
    Reporting group description
    		 Pazopanib 800 mg once daily, every 28 days

    Reporting group values
    		 Pazopanib and fosbretabulin Single-agent pazopanib Total
    Number of subjects
    		 11 10 21
    Age categorical
    Age at point of trial consent
    Units: Subjects
        Adults (18-64 years)
    		 9 5 14
        From 65-84 years
    		 2 5 7
        85 years and over
    		 0 0 0
    Age continuous
    Age at point of trial consent
    Units: years
        arithmetic mean (standard deviation)
    		 59.3 ± 8.3 60.3 ± 10.7 -
    Gender categorical
    Units: Subjects
        Female
    		 11 10 21
        Male
    		 0 0 0
    WHO performance status
    Units: Subjects
        00
    		 7 5 12
        01
    		 4 5 9
    Primary tumour location
    Units: Subjects
        Ovarian
    		 9 8 17
        Fallopian tubes
    		 1 1 2
        Primary peritoneal
    		 1 1 2
    Histology type
    Units: Subjects
        Serious
    		 10 9 19
        Endometrioid
    		 0 0 0
        Clear cell
    		 0 1 1
        Mucinous
    		 0 0 0
        Undifferentiated
    		 1 0 1
    Histological grade
    Units: Subjects
        High-grade
    		 10 10 20
        Low-grade
    		 0 0 0
        Unknown
    		 1 0 1
    FIGO stage at diagnosis
    Units: Subjects
        01
    		 0 3 3
        02
    		 2 0 2
        03
    		 9 6 15
        04
    		 0 1 1
    Prior bevacizumab
    Units: Subjects
        Yes
    		 3 2 5
        No
    		 8 8 16
    Platinum-free interval
    Units: Subjects
        ≤6 months
    		 6 7 13
        >6 months
    		 5 3 8
    Age at diagnosis
    Units: years
        arithmetic mean (full range (min-max))
    		 56.9 (42 to 71) 60.3 (31 to 68) -
    Prior lines of chemotherapy
    Units: prior lines
        median (full range (min-max))
    		 3 (1 to 4) 2 (1 to 5) -
    Subject analysis sets

    Subject analysis set title
    Phase 1b patients
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Twelve patients were enrolled in the Phase 1b trial. The primary endpoints of the phase 1b trial were to determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of pazopanib and fosbretabulin. The MTD was defined if no more than 1 patient, out of a maximum of 6 patients at the same dose level, experienced a DLT. Initially, 3 patients received dose level 1 and 3 patients received dose level 2 without a DLT. However due to multiple delayed grade ≥ 2 toxicities at dose level 2, experienced by patients after completing cycle 1; in particular hypertension and neutropenia, dose level 2 was expanded by a further 3 patients in order to elucidate better the toxicity profile. One of these 3 patients developed a DLT, reported as grade 3 fatigue, and dose level 2 was defined as the MTD. Consequently, dose level 1 was also expanded to include another 3 patients, and no DLTs were reported. Therefore, dose level 1 (600mg Pazopanib OD) was defined as the RP2D.

    Subject analysis sets values
    		 Phase 1b patients
    Number of subjects
    12
    Age categorical
    Age at point of trial consent
    Units: Subjects
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Age at point of trial consent
    Units: years
        arithmetic mean (standard deviation)
    ±
    Gender categorical
    Units: Subjects
        Female
        Male
    WHO performance status
    Units: Subjects
        00
    7
        01
    5
    Primary tumour location
    Units: Subjects
        Ovarian
    12
        Fallopian tubes
    0
        Primary peritoneal
    0
    Histology type
    Units: Subjects
        Serious
    11
        Endometrioid
    1
        Clear cell
    0
        Mucinous
    0
        Undifferentiated
    0
    Histological grade
    Units: Subjects
        High-grade
    11
        Low-grade
    1
        Unknown
    0
    FIGO stage at diagnosis
    Units: Subjects
        01
    0
        02
    0
        03
    9
        04
    3
    Prior bevacizumab
    Units: Subjects
        Yes
    2
        No
    10
    Platinum-free interval
    Units: Subjects
        ≤6 months
        >6 months
    Age at diagnosis
    Units: years
        arithmetic mean (full range (min-max))
    58.8 (40 to 70)
    Prior lines of chemotherapy
    Units: prior lines
        median (full range (min-max))
    5 (1 to 10)

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Pazopanib and fosbretabulin
    Reporting group description
    		 Pazopanib 600 mg once daily and fosbretabulin 54 mg/m2 on days 1, 8, 15, every 28 days

    Reporting group title
    Single-agent pazopanib
    Reporting group description
    		 Pazopanib 800 mg once daily, every 28 days

    Subject analysis set title
    Phase 1b patients
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Twelve patients were enrolled in the Phase 1b trial. The primary endpoints of the phase 1b trial were to determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of pazopanib and fosbretabulin. The MTD was defined if no more than 1 patient, out of a maximum of 6 patients at the same dose level, experienced a DLT. Initially, 3 patients received dose level 1 and 3 patients received dose level 2 without a DLT. However due to multiple delayed grade ≥ 2 toxicities at dose level 2, experienced by patients after completing cycle 1; in particular hypertension and neutropenia, dose level 2 was expanded by a further 3 patients in order to elucidate better the toxicity profile. One of these 3 patients developed a DLT, reported as grade 3 fatigue, and dose level 2 was defined as the MTD. Consequently, dose level 1 was also expanded to include another 3 patients, and no DLTs were reported. Therefore, dose level 1 (600mg Pazopanib OD) was defined as the RP2D.

    Primary: Phase II: Progression-free survival

    		 Close Top of page
    End point title
    		 Phase II: Progression-free survival
    End point description
    The primary objective of the randomised phase 2 trial was to determine whether combining pazopanib with fosbretabulin significantly improved PFS compared to single-agent pazopanib in recurrent advanced ovarian cancer.
    End point type
    Primary
    End point timeframe
    Progression-free survival was defined as the date from randomisation to the first date of either progressive disease (according to RECIST v1.1) or death.
    End point values
    		 Pazopanib and fosbretabulin Single-agent pazopanib
    Number of subjects analysed
    11
    10
    Units: Months
        median (confidence interval 95%)
    7.6 (4.1 to 999)
    3.7 (1.0 to 8.1)
    Statistical analysis title
    		 Efficacy analysis of Progression-free survival
    Statistical analysis description
    The phase 2 trial was powered to detect a PFS Hazard Ratio (HR) of 0.65 in the pazopanib and fosbretabulin group versus the pazopanib group (equivalent to an improvement in PFS at 6 months from 20% to 35%).
    Comparison groups
    Pazopanib and fosbretabulin v Single-agent pazopanib
    Number of subjects included in analysis
    21
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.06
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.08
         upper limit
    		 1.03
    Notes
    [1] - The primary analysis method was a Cox regression with the trial arm as the key covariate and adjusting for the two binary factors controlled for in the randomisation algorithm (platinum-free interval: >6 versus ≤6 months and prior bevacizumab treatment: yes/no).

    Primary: Phase 1b: maximum tolerated dose (MTD) of pazopanib and fosbretabulin

    		 Close Top of page
    End point title
    		 Phase 1b: maximum tolerated dose (MTD) of pazopanib and fosbretabulin [2]
    End point description
    The primary endpoints of the phase 1b trial were to determine the dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of pazopanib and fosbretabulin; defined if no more than 1 patient, out of a maximum of 6 patients at the same dose level, experienced a DLT. - dose level 1: pazopanib 600 mg OD and fosbretabulin 54 mg/m2 days 1, 8, 15, every 28 days - dose level 2: pazopanib 800 mg OD and fosbretabulin 54 mg/m2 days 1, 8, 15, every 28 days Initially, 3 patients received dose level 1 and 3 patients received dose level 2 without a DLT. However due to multiple delayed grade ≥ 2 toxicities at dose level 2, dose level 2 was expanded by a further 3 patients (6 total). One of these 3 patients developed a DLT, reported as grade 3 fatigue, and dose level 2 was defined as the MTD. Dose level 1 was expanded by a further 3 patients (6 total) and no further DLTs were reported. Consequently, dose level 1 was defined as the R2PD.
    End point type
    Primary
    End point timeframe
    From screening until progressive disease or intolerable toxicity
    Notes
    [2] - 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 dose finding phase 1b trial did not necessitate a formal statistical analysis. MTD was defined as the dose level where no more than 1 DLT was experienced.
    End point values
    		 Phase 1b patients
    Number of subjects analysed
    12
    Units: Number of patients who experienced DLT
        Number of DLTs at dose level 1
    0
        Number of DLTs at dose level 2
    1
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    All AEs including SAEs must be reported for eligible patients from the time of registration/randomisation until 30 days after the last dose of IMP or until resolution (whichever is the later).
    Adverse event reporting additional description
    Adverse events causally related to either Pazopanib or fosbretabulin, across both trial phases.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Phase II: Pazopanib alone
    Reporting group description
    		 -

    Reporting group title
    Phase 1b: Pazopanib 600 mg plus fosbretabulin
    Reporting group description
    		 -

    Reporting group title
    Phase 1b: Pazopanib 800 mg plus fosbretabulin
    Reporting group description
    		 -

    Reporting group title
    Phase II: Pazopanib and fosbretabulin
    Reporting group description
    		 -

    Serious adverse events
    		 Phase II: Pazopanib alone Phase 1b: Pazopanib 600 mg plus fosbretabulin Phase 1b: Pazopanib 800 mg plus fosbretabulin Phase II: Pazopanib and fosbretabulin
    Total subjects affected by serious adverse events
         subjects affected / exposed
    5 / 10 (50.00%)
    1 / 6 (16.67%)
    3 / 6 (50.00%)
    3 / 11 (27.27%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Investigations
    AST/ALT increased
    Additional description: AST/ALT increased
         subjects affected / exposed
    3 / 10 (30.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Thromboembolic Event
    Additional description: Thromboembolic Event
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
    Additional description: Hypertension
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial infarction
    Additional description: Myocardial infarction
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sinus bradycardia
    Additional description: Sinus bradycardia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile Neutropenia
    Additional description: Febrile Neutropenia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
    Additional description: Fatigue
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Intestinal perforation
    Additional description: Intestinal perforation
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Phase II: Pazopanib alone Phase 1b: Pazopanib 600 mg plus fosbretabulin Phase 1b: Pazopanib 800 mg plus fosbretabulin Phase II: Pazopanib and fosbretabulin
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 10 (70.00%)
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    10 / 11 (90.91%)
    Investigations
    GGT increased
    Additional description: GGT increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Blood bilirubin increased
    Additional description: Blood bilirubin increased
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
         occurrences all number
    0
    2
    1
    0
    AST/ALT increased
    Additional description: AST/ALT increased
         subjects affected / exposed
    0 / 10 (0.00%)
    5 / 6 (83.33%)
    3 / 6 (50.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    5
    3
    0
    Neutrophil count decreased
    Additional description: Neutrophil count decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    4 / 6 (66.67%)
    3 / 6 (50.00%)
    2 / 11 (18.18%)
         occurrences all number
    1
    4
    3
    2
    Platelet count decreased
    Additional description: Platelet count decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Vascular disorders
    Hypertension
    Additional description: Hypertension
         subjects affected / exposed
    2 / 10 (20.00%)
    5 / 6 (83.33%)
    5 / 6 (83.33%)
    6 / 11 (54.55%)
         occurrences all number
    2
    5
    5
    6
    Nervous system disorders
    Dysgeusia
    Additional description: Dysgeusia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Syncope
    Additional description: Syncope
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    1
    Blood and lymphatic system disorders
    Anaemia
    Additional description: Anaemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    1
    1
    General disorders and administration site conditions
    Fatigue
    Additional description: Fatigue
         subjects affected / exposed
    1 / 10 (10.00%)
    5 / 6 (83.33%)
    5 / 6 (83.33%)
    3 / 11 (27.27%)
         occurrences all number
    1
    5
    5
    3
    Chest pain
    Additional description: Chest pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    1
    1
    Non-specific pain
    Additional description: Non-specific pain
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    1
    0
    Gastrointestinal disorders
    Abdominal pain
    Additional description: Abdominal pain
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 6 (33.33%)
    4 / 6 (66.67%)
    1 / 11 (9.09%)
         occurrences all number
    0
    2
    4
    1
    Constipation
    Additional description: Constipation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 6 (16.67%)
    3 / 6 (50.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    1
    3
    1
    Diarrhoea
    Additional description: Diarrhoea
         subjects affected / exposed
    2 / 10 (20.00%)
    5 / 6 (83.33%)
    6 / 6 (100.00%)
    0 / 11 (0.00%)
         occurrences all number
    2
    5
    6
    0
    Dyspepsia
    Additional description: Dyspepsia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    0 / 11 (0.00%)
         occurrences all number
    0
    1
    2
    0
    Nausea
    Additional description: Nausea
         subjects affected / exposed
    0 / 10 (0.00%)
    4 / 6 (66.67%)
    5 / 6 (83.33%)
    0 / 11 (0.00%)
         occurrences all number
    0
    4
    5
    0
    Mucositis oral
    Additional description: Mucositis oral
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    1
    Oral mucositis
    Additional description: Oral mucositis
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 6 (50.00%)
    5 / 6 (83.33%)
    0 / 11 (0.00%)
         occurrences all number
    0
    3
    5
    0
    Vomiting
    Additional description: Vomiting
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 6 (33.33%)
    4 / 6 (66.67%)
    1 / 11 (9.09%)
         occurrences all number
    1
    2
    4
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
    Additional description: Dyspnoea
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 11 (0.00%)
         occurrences all number
    1
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Rash
    Additional description: Rash
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    0 / 11 (0.00%)
         occurrences all number
    0
    2
    1
    0
    Pruritus
    Additional description: Pruritus
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    1
    PPE syndrome
    Additional description: PPE syndrome
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 11 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Renal and urinary disorders
    Proteinuria
    Additional description: Proteinuria
         subjects affected / exposed
    0 / 10 (0.00%)
    4 / 6 (66.67%)
    3 / 6 (50.00%)
    0 / 11 (0.00%)
         occurrences all number
    0
    4
    3
    0
    Metabolism and nutrition disorders
    Anorexia
    Additional description: Anorexia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    1
    Hypophosphataemia
    Additional description: Hypophosphataemia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 11 (9.09%)
         occurrences all number
    0
    0
    0
    1
    Hypomagnesaemia
    Additional description: Hypomagnesaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    2 / 11 (18.18%)
         occurrences all number
    1
    0
    0
    2

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Mar 2015
    Substantial amendment 01: Update to Fosbretabulin Investigational Medicinal product Dossier (IMPD) due to change in manufacturer.
    18 Mar 2015
    Substantial amendment 02: Protocol version change 1.0 to 2.0. Allows patient to continue to receive both IMPs for more than 6 cycles until disease progression.
    17 Mar 2016
    Substantial amendment 03: Protocol version change 2.0 to 3.0. 1) Clarification about phase II follow up times and new secondary objective and endpoint added, 2) Update to eligibility criteria, 3) Change in translational research sample collection
    23 Feb 2017
    Substantial amendment 04: Protocol version change 3.0 to 4.0. 1) update to eligibility criteria, 2) update of IMP manufacturers name.
    12 Jun 2017
    Substantial amendment 05: Safety measure implementation. Treatment with fosbrestabulin temporarily suspended while investigation into SAE events takes place.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    02 Jun 2017
    The decision was made to bring the Phase II trial to early termination due to safety concerns in regards to the emergence of treatment-related, reversible myocardial injury. In the phase 1b trial, 2 patients developed treatment-related cardiac adverse events. In the randomised phase II trial, grade 3 cardiac events were reported in 2 additional patients. As a result, IMP and funding provider Novartis made the decision to discontinue the Phase II trial on safety grounds with immediate effect.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/31932108
    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-Tue May 07 06:53:38 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA