Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    A Phase II trial to assess FOLFIRI + aflibercept efficacy in patients with oxaliplatin-pretreated metastatic colorectal cancer with or without ACE polymorphisms

    Summary
    EudraCT number
    		 2016-001508-45
    Trial protocol
    		 ES  
    Global end of trial date
    11 Dec 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    26 Jun 2020
    First version publication date
    26 Jun 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    TTD-16-02
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02970916
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Grupo de Tratamiento de los Tumores Digestivos (TTD)
    Sponsor organisation address
    C/ Téllez Nº 30 posterior 1º oficina 4.2, Madrid, Spain, 28007
    Public contact
    TTD, Grupo de Tratamiento de los Tumores Digestivos (TTD), 0034 91 378 82 75, ttd@ttdgroup.org
    Scientific contact
    TTD, Grupo de Tratamiento de los Tumores Digestivos (TTD), 0034 91 378 82 75, ttd@ttdgroup.org
    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
    04 Sep 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    11 Dec 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    11 Dec 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess FOLFIRI + aflibercept efficacy in patients with or without angiotensin converting enzyme (ACE) polymorphisms in terms of progression-free survival (PFS).
    Protection of trial subjects
    All patients included in the clinical trial received the combination of aflibercept + FOLFIRI regimen in 2-week cycles. Treatment was given until disease progression, unacceptable toxicity or patient withdrawal (investigator or patient decision, death, appearance of any of the exclusion criteria clinically relevant, significant non-compliance with protocol, development of a second cancer, addition of an anti-neoplastic drug other tan study drugs or pregnancy). All patients that discontinued the study treatment were followed up every 3 months to document progression (If patients withdraw from the treatment before progression), treatment-related adverse events (AE), further cancer treatments and survival, except for those who withdrew their informed consent, were lost to follow-up or died.
    Background therapy
    		 Not applicable
    Evidence for comparator
    		 -
    Actual start date of recruitment
    23 Nov 2016
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 12 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 101
    Worldwide total number of subjects
    101
    EEA total number of subjects
    101
    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)
    57
    From 65 to 84 years
    44
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 One hundred and fifteen patients were recruited, 14 of whom were considered screening failures (noncompliance with selection criteria, n=11; withdrawal of consent n=2 and not possible to evaluate RECIST criteria due to patient`s weight, n=1). Therefore, 101 patients were finally included in this national study conducted in 15 Spanish hospitals.

    Pre-assignment
    Screening details
    		 Patients aged ≥18 years, with histologically proven colorectal adenocarcinoma, metastatic disease and ≥1 measurable unidimensional lesion using CT or MRI according to RECIST criteria. The mCRC had to be resistant to or progressive on an oxaliplatin-containing regimen. WHO performance status 0-2 and adequate bone marrow, renal and liver functions.

    Period 1
    Period 1 title
    Baseline (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded
    Blinding implementation details
    Not applicable.

    Arms
    Arm title
    		 Aflibercept + FOLFIRI
    Arm description
    		 All patients included in the clinical trial received the combination of aflibercept + FOLFIRI regimen in 2-week cycles. Treatment was given until disease progression, unacceptable toxicity or patient withdrawal (investigator or patient decision, death, appearance of any of the exclusion criteria clinically relevant, significant non-compliance with protocol, development of a second cancer, addition of an anti-neoplastic drug other tan study drugs or pregnancy).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Aflibercept
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Aflibercept was administered at a dose of 4 mg/kg by intravenous infusion on day 1 of each 2-week cycle.

    Investigational medicinal product name
    FOLFIRI
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    FOLFIRI regimen was administered immediately after aflibercept: Irinotecan: was administered at a dose of 180 mg/m2 Folinic acid: was administered at a dose of 400 mg/m2 (400 mg/m2 [racemic] or 200 mg/m2 [L-form]) by i.v. infusion followed by 5-Fluorouracil (5-FU) bolus: was administered at a dose of 400 mg/m2 as a bolus followed by 5-FU infusion: was administered at a dose of 2400 mg/m2 over 46 hours by continuous i.v. infusion.

    Number of subjects in period 1
    		Aflibercept + FOLFIRI
    Started
    101
    Completed
    101

    Baseline characteristics

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

    Reporting group values
    		 Baseline Total
    Number of subjects
    		 101 101
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 57 57
        From 65-84 years
    		 44 44
    Age continuous
    Units: years
        median (inter-quartile range (Q1-Q3))
    		 63.8 (57.7 to 71.3) -
    Gender categorical
    Units: Subjects
        Female
    		 41 41
        Male
    		 60 60
    ACE polymorphisms
    The genotype frequencies of the ACE polymorphisms.
    Units: Subjects
        IN/DEL
    		 47 47
        IN/IN
    		 14 14
        DEL/DEL
    		 40 40
    AGTR1 polymorphisms
    The genotype frequencies of the AGTR1 polymorphisms.
    Units: Subjects
        A/A
    		 54 54
        A/C
    		 38 38
        C/C
    		 9 9
    RAS status
    Units: Subjects
        Mutant
    		 60 60
        Wild-type
    		 34 34
        Unknown
    		 7 7
    ACE serum levels
    Units: ng/ml
        median (inter-quartile range (Q1-Q3))
    		 161.2 (82.5 to 320.6) -
    VEGF-A serum levels
    Units: ng/ml
        median (inter-quartile range (Q1-Q3))
    		 1.6 (0.3 to 15.8) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Aflibercept + FOLFIRI
    Reporting group description
    		 All patients included in the clinical trial received the combination of aflibercept + FOLFIRI regimen in 2-week cycles. Treatment was given until disease progression, unacceptable toxicity or patient withdrawal (investigator or patient decision, death, appearance of any of the exclusion criteria clinically relevant, significant non-compliance with protocol, development of a second cancer, addition of an anti-neoplastic drug other tan study drugs or pregnancy).

    Subject analysis set title
    ITT
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Intention to treat (ITT) population: included all patients receiving at least one dose of study treatment and with quality DNA sample available for biomarker determination (N=101).

    Subject analysis set title
    PP
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Per protocol (PP) population: included all patients who met all the inclusion criteria and none of the exclusion criteria who received the study treatment as per the protocol, had at least one assessment of efficacy and/or safety post-baseline and without major protocol deviations that entailed patient's withdrawal from the study (N=89).

    Subject analysis set title
    IN/DEL
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    ACE polymorphism IN/DEL

    Subject analysis set title
    IN/IN
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    ACE polymorphism IN/IN

    Subject analysis set title
    DEL/DEL
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    ACE polymorphism DEL/DEL

    Subject analysis set title
    <1.941 ng/ml
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    VEFG-A levels <1.941 ng/ml

    Subject analysis set title
    ≥1.941 ng/ml
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    VEFG-A levels ≥1.941 ng/ml

    Primary: Progression-free survival (PFS)

    		 Close Top of page
    End point title
    		 Progression-free survival (PFS) [1]
    End point description
    The primary study endpoint was PFS, defined as the time from inclusion to disease progression (observed radiologically) or death from any cause.
    End point type
    Primary
    End point timeframe
    From inclusion to disease progression or death from any cause.
    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: Absolute and relative frequency distributions were presented for qualitative variables, as well as measures of central tendency and dispersion for quantitative variables. The Kaplan–Meier method was used to analyse the primary and secondary time-to-event endpoints.
    End point values
    		 ITT PP
    Number of subjects analysed
    101
    89
    Units: months
        median (confidence interval 95%)
    7.5 (6.0 to 8.9)
    8.4 (6.9 to 9.8)
    No statistical analyses for this end point

    Secondary: Overall surival (OS)

    		 Close Top of page
    End point title
    		 Overall surival (OS)
    End point description
    OS was defined as time from inclusion to death from any cause
    End point type
    Secondary
    End point timeframe
    From inclusion to death from any cause.
    End point values
    		 ITT
    Number of subjects analysed
    101
    Units: months
        median (confidence interval 95%)
    12.6 (8.4 to 16.8)
    No statistical analyses for this end point

    Secondary: Time to progression (TTP)

    		 Close Top of page
    End point title
    		 Time to progression (TTP)
    End point description
    Time from inclusion to disease progression or death for progression
    End point type
    Secondary
    End point timeframe
    From inclusion to disease progression or death for progression
    End point values
    		 ITT
    Number of subjects analysed
    101
    Units: months
        median (confidence interval 95%)
    8.3 (7.1 to 9.6)
    No statistical analyses for this end point

    Secondary: Time to treatment failure (TTF)

    		 Close Top of page
    End point title
    		 Time to treatment failure (TTF)
    End point description
    Time from inclusion to treatment discontinuation for any reason.
    End point type
    Secondary
    End point timeframe
    From inclusion to treatment discontinuation.
    End point values
    		 ITT
    Number of subjects analysed
    101
    Units: months
        median (confidence interval 95%)
    6.1 (4.8 to 7.4)
    No statistical analyses for this end point

    Secondary: Overall response rate (ORR)

    		 Close Top of page
    End point title
    		 Overall response rate (ORR)
    End point description
    Percentage of patients with either a complete response (CR) or partial response (PR) according to RECIST criteria (version 1.1).
    End point type
    Secondary
    End point timeframe
    From the beginning until the end of the study.
    End point values
    		 ITT
    Number of subjects analysed
    101 [2]
    Units: Percentage of patients
        number (confidence interval 95%)
    15.8 (9.6 to 24.8)
    Notes
    [2] - PR was reported in 15.8% (n=16).
    No statistical analyses for this end point

    Secondary: Disease control rate (DCR)

    		 Close Top of page
    End point title
    		 Disease control rate (DCR)
    End point description
    Percentage of patients with either a complete response (CR), partial response (PR) or stable disease (SD) according to RECIST criteria (version 1.1).
    End point type
    Secondary
    End point timeframe
    From the beginning until the end of the study.
    End point values
    		 ITT
    Number of subjects analysed
    101 [3]
    Units: Percentage of patients
        median (confidence interval 95%)
    69.3 (59.2 to 77.9)
    Notes
    [3] - PR and SD were reported in 15.8% (n=16) and 53.5% (n=54) respectively.
    No statistical analyses for this end point

    Secondary: ORR according to ACE polymorphisms

    		 Close Top of page
    End point title
    		 ORR according to ACE polymorphisms
    End point description
    Percentage of patients with either a complete response (CR) or partial response (PR) according to RECIST criteria (version 1.1) and classified according to ACE polymorphisms.
    End point type
    Secondary
    End point timeframe
    From the beginning until the end of the study.
    End point values
    		 IN/DEL IN/IN DEL/DEL
    Number of subjects analysed
    47
    14
    40
    Units: Subjects
    9
    3
    7
    Statistical analysis title
    		 Fisher`s exact test
    Comparison groups
    IN/DEL v IN/IN v DEL/DEL
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.941
    Method
    		 Fisher exact
    Confidence interval

    Secondary: DCR according to ACE polymorphisms

    		 Close Top of page
    End point title
    		 DCR according to ACE polymorphisms
    End point description
    Percentage of patients with either a complete response (CR), partial response (PR) or stable disease (SD) according to RECIST criteria (version 1.1) and classified according ACE polymorphisms.
    End point type
    Secondary
    End point timeframe
    From the beginning until the end of the study.
    End point values
    		 IN/DEL IN/IN DEL/DEL
    Number of subjects analysed
    47
    14
    40
    Units: Subjects
    33
    9
    28
    Statistical analysis title
    		 Fisher`s exact test
    Comparison groups
    IN/DEL v IN/IN v DEL/DEL
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.913
    Method
    		 Fisher exact
    Confidence interval

    Secondary: PFS according to ACE polymorphisms

    		 Close Top of page
    End point title
    		 PFS according to ACE polymorphisms
    End point description
    PFS was defined as the time from inclusion to disease progression (observed radiologically) or death from any cause. Results a presented here according to ACE polymorphisms.
    End point type
    Secondary
    End point timeframe
    From inclusion to disease progression or death from any cause.
    End point values
    		 IN/DEL IN/IN DEL/DEL
    Number of subjects analysed
    47
    14
    40
    Units: months
        median (confidence interval 95%)
    9.0 (6.9 to 11.0)
    4.3 (0.0 to 9.4)
    7.4 (5.4 to 9.3)
    Statistical analysis title
    		 Log-Rank
    Comparison groups
    IN/DEL v IN/IN v DEL/DEL
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.854
    Method
    		 Logrank
    Confidence interval

    Secondary: OS according to ACE polymorphisms

    		 Close Top of page
    End point title
    		 OS according to ACE polymorphisms
    End point description
    Time from inclusion to death from any cause according to ACE polymorphisms.
    End point type
    Secondary
    End point timeframe
    From inclusion to death from any cause.
    End point values
    		 IN/DEL IN/IN DEL/DEL
    Number of subjects analysed
    47
    14
    40
    Units: months
        median (confidence interval 95%)
    15.5 (11.0 to 20.0)
    8.6 (0.7 to 16.5)
    10.4 (7.3 to 13.4)
    Statistical analysis title
    		 Log-Rank
    Comparison groups
    IN/DEL v IN/IN v DEL/DEL
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.689
    Method
    		 Logrank
    Confidence interval

    Secondary: TTP according to ACE polymorphisms

    		 Close Top of page
    End point title
    		 TTP according to ACE polymorphisms
    End point description
    Time from inclusion to disease progression or death for progression according to ACE polymorphisms.
    End point type
    Secondary
    End point timeframe
    From inclusion to disease progression or death for progression.
    End point values
    		 IN/DEL IN/IN DEL/DEL
    Number of subjects analysed
    47
    14
    40
    Units: months
        median (confidence interval 95%)
    9.0 (6.8 to 11.2)
    4.3 (0.0 to 9.4)
    7.4 (4.4 to 10.4)
    Statistical analysis title
    		 Log-Rank
    Comparison groups
    IN/DEL v IN/IN v DEL/DEL
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.828
    Method
    		 Logrank
    Confidence interval

    Secondary: TTF according to ACE polymorphisms

    		 Close Top of page
    End point title
    		 TTF according to ACE polymorphisms
    End point description
    Time from inclusion to treatment discontinuation for any reason according to ACE polymorphisms.
    End point type
    Secondary
    End point timeframe
    From inclusion to treatment discontinuation.
    End point values
    		 IN/DEL IN/IN DEL/DEL
    Number of subjects analysed
    47
    14
    40
    Units: months
        median (confidence interval 95%)
    7.1 (5.1 to 9.2)
    4.5 (2.1 to 7.0)
    5.4 (3.9 to 7.0)
    Statistical analysis title
    		 Log-Rank
    Comparison groups
    IN/DEL v IN/IN v DEL/DEL
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 = 0.477
    Method
    		 Logrank
    Confidence interval

    Secondary: OS according to VEGF-A levels

    		 Close Top of page
    End point title
    		 OS according to VEGF-A levels
    End point description
    Time from inclusion to death from any cause according to VEGF-A levels.
    End point type
    Secondary
    End point timeframe
    From inclusion to death from any cause.
    End point values
    		 <1.941 ng/ml ≥1.941 ng/ml
    Number of subjects analysed
    53
    47
    Units: months
        median (confidence interval 95%)
    18.9 (14.8 to 23.0)
    7.6 (4.5 to 10.7)
    Statistical analysis title
    		 Log-Rank
    Comparison groups
    <1.941 ng/ml v ≥1.941 ng/ml
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 < 0.001
    Method
    		 Logrank
    Confidence interval

    Other pre-specified: PFS according to VEGF-A levels

    		 Close Top of page
    End point title
    		 PFS according to VEGF-A levels
    End point description
    Time from inclusion to disease progression (observed radiologically) or death from any cause according to VEGF-A levels.
    End point type
    Other pre-specified
    End point timeframe
    From inclusion to disease progression or death from any cause.
    End point values
    		 <1.941 ng/ml ≥1.941 ng/ml
    Number of subjects analysed
    53
    47
    Units: months
        median (confidence interval 95%)
    9.2 (8.4 to 10.0)
    4.2 (2.7 to 5.6)
    Statistical analysis title
    		 Log-Rank
    Comparison groups
    <1.941 ng/ml v ≥1.941 ng/ml
    Number of subjects included in analysis
    100
    Analysis specification
    Pre-specified
    Analysis type
    		 equivalence
    P-value
    		 < 0.001
    Method
    		 Logrank
    Confidence interval

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    The treatment safety profile was a secondary endpoint, assessed according to AEs recorded throughout the study and the incidence of dose adjustments and compliance of study treatment.
    Adverse event reporting additional description
    The variables evaluated to characterize the AE profile of the treatment were their incidence and severity as per the NCI-CTCAE criteria (version 4.03).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.0
    Reporting groups
    Reporting group title
    Safety population
    Reporting group description
    		 -

    Serious adverse events
    		 Safety population
    Total subjects affected by serious adverse events
         subjects affected / exposed
    37 / 101 (36.63%)
         number of deaths (all causes)
    65
         number of deaths resulting from adverse events
    11
    Injury, poisoning and procedural complications
    Chemical peritonitis
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Ventricular dysfunction
    Additional description: Left ventricular systolic dysfunction
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Hepatic encephalopathy
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 101 (3.96%)
         occurrences causally related to treatment / all
    3 / 4
         deaths causally related to treatment / all
    0 / 0
    Death
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    Pyrexia
    Additional description: Febrile syndrome of persistent respiratory focus.
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    6 / 101 (5.94%)
         occurrences causally related to treatment / all
    1 / 6
         deaths causally related to treatment / all
    0 / 5
    Pain
         subjects affected / exposed
    2 / 101 (1.98%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    4 / 101 (3.96%)
         occurrences causally related to treatment / all
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 101 (2.97%)
         occurrences causally related to treatment / all
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Enterocolitis
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal toxicity
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    Intestinal obstruction
         subjects affected / exposed
    8 / 101 (7.92%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    Large intestine perforation
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Female genital tract fistula
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 101 (1.98%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    Pneumonitis
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 101 (1.98%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Nephritic syndrome
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    2 / 101 (1.98%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Appendicitis perforated
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Anal abscess
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 101 (0.99%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Safety population
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    101 / 101 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    37 / 101 (36.63%)
         occurrences all number
    76
    Nervous system disorders
    Headache
         subjects affected / exposed
    22 / 101 (21.78%)
         occurrences all number
    40
    Neurotoxicity
         subjects affected / exposed
    6 / 101 (5.94%)
         occurrences all number
    7
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    13 / 101 (12.87%)
         occurrences all number
    18
    Neutropenia
         subjects affected / exposed
    45 / 101 (44.55%)
         occurrences all number
    136
    Thrombocytopenia
         subjects affected / exposed
    8 / 101 (7.92%)
         occurrences all number
    27
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    75 / 101 (74.26%)
         occurrences all number
    282
    Fatigue
         subjects affected / exposed
    7 / 101 (6.93%)
         occurrences all number
    11
    General physical health deterioration
         subjects affected / exposed
    6 / 101 (5.94%)
         occurrences all number
    7
    Mucosal inflammation
         subjects affected / exposed
    58 / 101 (57.43%)
         occurrences all number
    162
    Oedema peripheral
         subjects affected / exposed
    8 / 101 (7.92%)
         occurrences all number
    8
    Pyrexia
         subjects affected / exposed
    15 / 101 (14.85%)
         occurrences all number
    30
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    6 / 101 (5.94%)
         occurrences all number
    6
    Abdominal pain
         subjects affected / exposed
    29 / 101 (28.71%)
         occurrences all number
    52
    Abdominal pain upper
         subjects affected / exposed
    10 / 101 (9.90%)
         occurrences all number
    11
    Constipation
         subjects affected / exposed
    19 / 101 (18.81%)
         occurrences all number
    22
    Diarrhoea
         subjects affected / exposed
    78 / 101 (77.23%)
         occurrences all number
    283
    Dysgeusia
         subjects affected / exposed
    14 / 101 (13.86%)
         occurrences all number
    18
    Dyspepsia
         subjects affected / exposed
    7 / 101 (6.93%)
         occurrences all number
    9
    Intestinal obstruction
         subjects affected / exposed
    6 / 101 (5.94%)
         occurrences all number
    8
    Nausea
         subjects affected / exposed
    34 / 101 (33.66%)
         occurrences all number
    72
    Odynophagia
         subjects affected / exposed
    8 / 101 (7.92%)
         occurrences all number
    9
    Proctalgia
         subjects affected / exposed
    10 / 101 (9.90%)
         occurrences all number
    23
    Rectal haemorrhage
         subjects affected / exposed
    8 / 101 (7.92%)
         occurrences all number
    12
    Stomatitis
         subjects affected / exposed
    7 / 101 (6.93%)
         occurrences all number
    13
    Vomiting
         subjects affected / exposed
    30 / 101 (29.70%)
         occurrences all number
    46
    Respiratory, thoracic and mediastinal disorders
    Aphonia
         subjects affected / exposed
    9 / 101 (8.91%)
         occurrences all number
    10
    Dysphonia
         subjects affected / exposed
    24 / 101 (23.76%)
         occurrences all number
    37
    Dyspnoea
         subjects affected / exposed
    7 / 101 (6.93%)
         occurrences all number
    11
    Epistaxis
         subjects affected / exposed
    31 / 101 (30.69%)
         occurrences all number
    50
    Nasopharyngitis
         subjects affected / exposed
    10 / 101 (9.90%)
         occurrences all number
    10
    Respiratory tract infection
         subjects affected / exposed
    9 / 101 (8.91%)
         occurrences all number
    12
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    22 / 101 (21.78%)
         occurrences all number
    29
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    6 / 101 (5.94%)
         occurrences all number
    9
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    9 / 101 (8.91%)
         occurrences all number
    10
    Proteinuria
         subjects affected / exposed
    10 / 101 (9.90%)
         occurrences all number
    16
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    10 / 101 (9.90%)
         occurrences all number
    12
    Musculoskeletal pain
         subjects affected / exposed
    7 / 101 (6.93%)
         occurrences all number
    10
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    31 / 101 (30.69%)
         occurrences all number
    48

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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.
    These preliminary results are exploratory and further analysis are required.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun Apr 28 21:47:24 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA