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   43866   clinical trials with a EudraCT protocol, of which   7287   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 randomised phase II trial assessing REGorafenib combined with IRInotecan as second-line treatment in patients with metastatic gastro-oesophageal adenocarcinomas.

    Summary
    EudraCT number
    		 2018-002374-46
    Trial protocol
    		 FR  
    Global end of trial date
    19 May 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    06 Jul 2023
    First version publication date
    06 Jul 2023
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    UC-0110/1807
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03722108
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    UNICANCER
    Sponsor organisation address
    101 rue de Tolbiac, Paris, France, 75013
    Public contact
    Nourredine AIT RAHMOUNE, UNICANCER, 33 0171936704, n.ait-rahmoune@unicancer.fr
    Scientific contact
    Nourredine AIT RAHMOUNE, UNICANCER, 33 0171936704, n.ait-rahmoune@unicancer.fr
    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
    24 Sep 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    19 May 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the efficacy of regorafenib combined with irinotecan (REGIRI), compared to irinotecan (IRI) alone, as second-line treatment in patients with metastatic gastro-oesophageal adenocarcinomas. The efficacy will be evaluated in terms of overall survival (OS).
    Protection of trial subjects
    An Independent Ethics Committees reviewed and gave a favorable opinion to the study documents, including the initial protocol and all subsequent amendments, and all information and documents provided to subjects/patients. This study was conducted in accordance with: -Declaration of Helsinki, as modified in 2008, -Loi n°2012-300 du 5 mars 2012 relative aux recherches impliquant la personne humaine, as modifed in 2016 -Regulation (EU) 2016/679 on the protection of natural persons with regard to the processing of personal data and on the free movement of such data (General Data Protection Regulation) -Amended Loi Informatique et Libertés n°78-17 du 6 janvier 1978, relative à la protection des personnes physiques à l'égard des traitements de données à caractère personnel, -Amended Loi n° 2004-800 du 6 août 2004, relative à la bioéthique, -Décision du 24 novembre 2006 fixant les règles de Bonnes Pratiques Cliniques pour les recherches biomédicales portant sur des médicaments à usage humain -Arrêté du 24 mai 2006 relatif au contenu et aux modalités de présentation d’un protocole de recherche biomédicale portant sur un médicament à usage humain-Good Manufacturing Practices, in particular, Annex 13 on investigational medicinal products.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Feb 2019
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 89
    Worldwide total number of subjects
    89
    EEA total number of subjects
    89
    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)
    53
    From 65 to 84 years
    36
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 89 subjects were randomized from 25/02/2019 to 21/09/2021 by 22 participating centers. Recruitment only in France.

    Pre-assignment
    Screening details
    		 The study population is composed of patients aged ≥18 years old, with metastatic gastrooesophageal adenocarcinomas after failure of first-line fluoropyrimidine and platinum-based chemotherapies. The trial consisted of a screening phase before randomization to establish eligibility: 108 patients was assessed for eligibility.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 REGIRI arm
    Arm description
    		 regorafenib combined with irinotecan: During the 4-week treatment cycle, irinotecan (180 mg/m2 ) will be infused intravenously over 90 min on day D1 and D15 of each cycle. Oral regorafenib (160 mg/day [4 x 40 mg tablets/day]) will be taken daily from D2-8 and D16-22 of each cycle. The patients will be treated until disease progression or until discontinuations of treatment for other reasons. Dose interruptions and modifications may be required depending on the individual patient’s treatment tolerance.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Regorafenib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Oral regorafenib (160 mg/day [4 x 40 mg tablets/day]) will be taken daily from D2-8 and D16-22 of each cycle.

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    During the 4-week treatment cycle, irinotecan (180 mg/m2) will be infused intravenously over 90 min on day D1 and D15 of each cycle.

    Arm title
    		 IRI arm
    Arm description
    		 Irinotecan alone: During the 4-week treatment cycle, irinotecan (180 mg/m2) will be infused intravenously over 90 min on D1 and D15 of each cycle. The patients will be treated until disease progression or until discontinuations of treatment for other reasons. Dose interruptions and modifications may be required depending on the individual patient’s treatment tolerance.
    Arm type
    		 Control

    Investigational medicinal product name
    Irinotecan
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    During the 4-week treatment cycle, irinotecan (180 mg/m2) will be infused intravenously over 90 min on D1 and D15 of each cycle.

    Number of subjects in period 1
    		REGIRI arm IRI arm
    Started
    44
    45
    Completed
    0
    2
    Not completed
    44
    43
         Physician decision
    -
    2
         Death
    2
    1
         Other
    -
    2
         Adverse event
    9
    5
         Progressive disease
    31
    30
         Biological progression
    -
    2
         Withdrawal by subject
    2
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    REGIRI arm
    Reporting group description
    		 regorafenib combined with irinotecan: During the 4-week treatment cycle, irinotecan (180 mg/m2 ) will be infused intravenously over 90 min on day D1 and D15 of each cycle. Oral regorafenib (160 mg/day [4 x 40 mg tablets/day]) will be taken daily from D2-8 and D16-22 of each cycle. The patients will be treated until disease progression or until discontinuations of treatment for other reasons. Dose interruptions and modifications may be required depending on the individual patient’s treatment tolerance.

    Reporting group title
    IRI arm
    Reporting group description
    		 Irinotecan alone: During the 4-week treatment cycle, irinotecan (180 mg/m2) will be infused intravenously over 90 min on D1 and D15 of each cycle. The patients will be treated until disease progression or until discontinuations of treatment for other reasons. Dose interruptions and modifications may be required depending on the individual patient’s treatment tolerance.

    Reporting group values
    		 REGIRI arm IRI arm Total
    Number of subjects
    		 44 45 89
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 26 27 53
        From 65-84 years
    		 18 18 36
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        median (full range (min-max))
    		 62 (34 to 82) 60 (28 to 80) -
    Gender categorical
    Units: Subjects
        Female
    		 40 37 77
        Male
    		 4 8 12
    Patient contraception?
    Units: Subjects
        Missing
    		 4 5 9
        NO
    		 0 3 3
        YES
    		 40 37 77
    Location of tumour
    Units: Subjects
        GASTROESOPHAGEAL JUNCTION ADENOCARCINOMA
    		 30 30 60
        GASTRIC ADENOCARCINOMA
    		 14 15 29
    Histological type
    Units: Subjects
        OTHER
    		 2 4 6
        LIEBERKUHNIEN ADENOCARCINOMA
    		 22 27 49
        MUCINOUS ADENOCARCINOMA
    		 1 1 2
        DUCTAL ADENOCARCINOMA
    		 7 4 11
        PAPILLARY ADENOCARCINOMA
    		 2 1 3
        INDEPENDENT CELLS ADENOCARCINOMA
    		 7 7 14
        MIXED ADENOCARCINOMA
    		 3 1 4
    HER2 STATUS
    Units: Subjects
        Missing
    		 6 4 10
        HER2+
    		 9 9 18
        HER2-
    		 29 32 61
    Synchronous metastases
    Units: Subjects
        NO
    		 16 19 35
        YES
    		 28 26 54
    Previous chemotherapy
    Units: Subjects
        YES
    		 44 45 89
    Previous radiotherapy
    Units: Subjects
        NO
    		 35 39 74
        YES
    		 9 6 15
    Previous surgery
    Units: Subjects
        NO
    		 27 27 54
        YES
    		 17 18 35
    Previous other cancer therapy
    Units: Subjects
        NO
    		 38 36 74
        YES
    		 6 9 15

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    REGIRI arm
    Reporting group description
    		 regorafenib combined with irinotecan: During the 4-week treatment cycle, irinotecan (180 mg/m2 ) will be infused intravenously over 90 min on day D1 and D15 of each cycle. Oral regorafenib (160 mg/day [4 x 40 mg tablets/day]) will be taken daily from D2-8 and D16-22 of each cycle. The patients will be treated until disease progression or until discontinuations of treatment for other reasons. Dose interruptions and modifications may be required depending on the individual patient’s treatment tolerance.

    Reporting group title
    IRI arm
    Reporting group description
    		 Irinotecan alone: During the 4-week treatment cycle, irinotecan (180 mg/m2) will be infused intravenously over 90 min on D1 and D15 of each cycle. The patients will be treated until disease progression or until discontinuations of treatment for other reasons. Dose interruptions and modifications may be required depending on the individual patient’s treatment tolerance.

    Primary: Overall survival (OS)

    		 Close Top of page
    End point title
    		 Overall survival (OS)
    End point description
    Survival rates will be estimated according to Kaplan-Meier. If a patient is alive at the database cut-off date, then the patient will be censored at the last date of follow-up.
    End point type
    Primary
    End point timeframe
    The primary endpoint was OS, defined as the time from the date of randomisation until death of any cause.
    End point values
    		 REGIRI arm IRI arm
    Number of subjects analysed
    44
    45
    Units: Months
        median (confidence interval 95%)
    6.3 (5.2 to 7.1)
    8.2 (5.4 to 9.7)
    Statistical analysis title
    		 OS analysis
    Comparison groups
    REGIRI arm v IRI arm
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.66
    Method
    		 Log-rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.74

    Secondary: Overall survival rates

    		 Close Top of page
    End point title
    		 Overall survival rates
    End point description
    OS rates at 6 and 12 months were estimated by the Kaplan-Meier method
    End point type
    Secondary
    End point timeframe
    at 6 and 12 months
    End point values
    		 REGIRI arm IRI arm
    Number of subjects analysed
    44
    45
    Units: percent
    median (confidence interval 95%)
        6 months
    54.6 (38.8 to 67.8)
    60.0 (44.3 to 72.6)
        12 months
    25.0 (13.5 to 38.4)
    23.5 (12.3 to 36.7)
    Statistical analysis title
    		 OS analysis
    Comparison groups
    REGIRI arm v IRI arm
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.66
    Method
    		 Log-rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.7
         upper limit
    		 1.74

    Secondary: Progression-free survival (PFS)

    		 Close Top of page
    End point title
    		 Progression-free survival (PFS)
    End point description
    Progression free survival (PFS) was defined as the time from the date of randomization to the date of disease progression (radiological or clinical) or death of any cause, whichever occured first. Patients without tumour progression or alive at the time of analysis were censored at the date of their last tumour assessment.
    End point type
    Secondary
    End point timeframe
    From the date of randomization to the date of disease progression (radiological or clinical) or death of any cause, whichever occured first.
    End point values
    		 REGIRI arm IRI arm
    Number of subjects analysed
    44
    45
    Units: Months
        median (confidence interval 95%)
    2.2 (1.8 to 3.6)
    1.9 (1.7 to 2.1)
    Statistical analysis title
    		 PFS analysis
    Comparison groups
    REGIRI arm v IRI arm
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.76
    Method
    		 Log-rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 1.45

    Secondary: PFS rates at 3 and 6 months

    		 Close Top of page
    End point title
    		 PFS rates at 3 and 6 months
    End point description
    End point type
    Secondary
    End point timeframe
    At 3-month and 6-month after randomization.
    End point values
    		 REGIRI arm IRI arm
    Number of subjects analysed
    44
    45
    Units: Months
    median (confidence interval 95%)
        3 months
    40.9 (26.5 to 54.8)
    33.3 (20.2 to 47.0)
        6 months
    18.2 (8.5 to 30.7)
    20.0 (9.9 to 32.7)
    Statistical analysis title
    		 PFS analysis
    Comparison groups
    REGIRI arm v IRI arm
    Number of subjects included in analysis
    89
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.76
    Method
    		 Log-rank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 1.45

    Secondary: Disease control rate (DCR)

    		 Close Top of page
    End point title
    		 Disease control rate (DCR)
    End point description
    DCR will be compared between treatment groups using the Cochran-Mantel-Haenszel test.
    End point type
    Secondary
    End point timeframe
    Disease control rate (DCR) was defined as the percentage of patients with complete response (CR), partial response (PR), or stable disease (SD) as best response at the database cut-off date.
    End point values
    		 REGIRI arm IRI arm
    Number of subjects analysed
    44
    45
    Units: percent
        number (not applicable)
    45.5
    33.3
    No statistical analyses for this end point

    Secondary: Objective response rate (ORR)

    		 Close Top of page
    End point title
    		 Objective response rate (ORR)
    End point description
    Objective response rate will be compared between treatment groups using the Cochran-Mantel-Haenszel test.
    End point type
    Secondary
    End point timeframe
    Objective response rate (ORR)was defined as the percentage of patients with CR or PR. Patients who discontinued their treatment without a tumour assessment were considered nonresponders for the analysis.
    End point values
    		 REGIRI arm IRI arm
    Number of subjects analysed
    44
    45
    Units: percent
        number (not applicable)
    15.9
    13.3
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From randomization until 30 days after end of treatment (up to 5 years).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22
    Reporting groups
    Reporting group title
    REGIRI arm
    Reporting group description
    		 -

    Reporting group title
    IRI arm
    Reporting group description
    		 -

    Serious adverse events
    		 REGIRI arm IRI arm
    Total subjects affected by serious adverse events
         subjects affected / exposed
    22 / 44 (50.00%)
    17 / 43 (39.53%)
         number of deaths (all causes)
    39
    40
         number of deaths resulting from adverse events
    4
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Peritoneal carcinosis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour pain
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tumour perforation
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    Malignant neoplasm progression
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Pulmonary embolism
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Deep vein thrombosis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombotic microangiopathy
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    2 / 44 (4.55%)
    4 / 43 (9.30%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 4
    Pain
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 44 (6.82%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    3 / 3
    1 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 43 (4.65%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastric perforation
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal pain
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Oesophageal stenosis
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Retroperitoneal haematoma
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal stenosis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Hepatic cytolysis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Catheter site infection
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 REGIRI arm IRI arm
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    44 / 44 (100.00%)
    43 / 43 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to peritoneum
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Tumour perforation
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Vascular disorders
    Hot flush
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    0
    4
    HYPERTENSION
         subjects affected / exposed
    10 / 44 (22.73%)
    0 / 43 (0.00%)
         occurrences all number
    25
    0
    Hypotension
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences all number
    3
    0
    Pulmonary embolism
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences all number
    3
    0
    Raynaud's phenomenon
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Venous thrombosis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    30 / 44 (68.18%)
    25 / 43 (58.14%)
         occurrences all number
    151
    93
    Chest discomfort
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Chest pain
         subjects affected / exposed
    5 / 44 (11.36%)
    1 / 43 (2.33%)
         occurrences all number
    11
    1
    Chills
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Disease progression
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Early satiety
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Fatigue
         subjects affected / exposed
    7 / 44 (15.91%)
    4 / 43 (9.30%)
         occurrences all number
    20
    16
    General physical health deterioration
         subjects affected / exposed
    5 / 44 (11.36%)
    7 / 43 (16.28%)
         occurrences all number
    6
    13
    Generalised oedema
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Hypothermia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Malaise
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Mucosal inflammation
         subjects affected / exposed
    8 / 44 (18.18%)
    4 / 43 (9.30%)
         occurrences all number
    15
    6
    Mucosal toxicity
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Oedema peripheral
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 43 (6.98%)
         occurrences all number
    4
    4
    Pain
         subjects affected / exposed
    3 / 44 (6.82%)
    4 / 43 (9.30%)
         occurrences all number
    3
    10
    Peripheral swelling
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    1 / 44 (2.27%)
    4 / 43 (9.30%)
         occurrences all number
    1
    8
    Xerosis
         subjects affected / exposed
    3 / 44 (6.82%)
    1 / 43 (2.33%)
         occurrences all number
    4
    2
    Immune system disorders
    Anaphylactic shock
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Intermenstrual bleeding
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    3
    Pelvic pain
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    2
    Dysphonia
         subjects affected / exposed
    8 / 44 (18.18%)
    1 / 43 (2.33%)
         occurrences all number
    15
    1
    Dyspnoea
         subjects affected / exposed
    7 / 44 (15.91%)
    2 / 43 (4.65%)
         occurrences all number
    12
    2
    Dyspnoea exertional
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Hiccups
         subjects affected / exposed
    6 / 44 (13.64%)
    0 / 43 (0.00%)
         occurrences all number
    9
    0
    Laryngeal pain
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Lung disorder
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    2
    Oropharyngeal pain
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Rales
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Rhinorrhoea
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    7 / 44 (15.91%)
    0 / 43 (0.00%)
         occurrences all number
    18
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    5 / 44 (11.36%)
    1 / 43 (2.33%)
         occurrences all number
    18
    1
    Confusional state
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Insomnia
         subjects affected / exposed
    3 / 44 (6.82%)
    1 / 43 (2.33%)
         occurrences all number
    6
    6
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    2 / 44 (4.55%)
    2 / 43 (4.65%)
         occurrences all number
    8
    9
    Aspartate aminotransferase increased
         subjects affected / exposed
    2 / 44 (4.55%)
    2 / 43 (4.65%)
         occurrences all number
    6
    5
    Blood alkaline phosphatase increased
         subjects affected / exposed
    2 / 44 (4.55%)
    3 / 43 (6.98%)
         occurrences all number
    2
    5
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    3 / 44 (6.82%)
    5 / 43 (11.63%)
         occurrences all number
    3
    7
    Intestinal transit time increased
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Lipase increased
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences all number
    2
    1
    Platelet count decreased
         subjects affected / exposed
    3 / 44 (6.82%)
    1 / 43 (2.33%)
         occurrences all number
    3
    1
    Weight decreased
         subjects affected / exposed
    16 / 44 (36.36%)
    3 / 43 (6.98%)
         occurrences all number
    32
    4
    Injury, poisoning and procedural complications
    Limb injury
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Overdose
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Radiation oesophagitis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Palpitations
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Anosmia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Cholinergic syndrome
         subjects affected / exposed
    2 / 44 (4.55%)
    1 / 43 (2.33%)
         occurrences all number
    2
    1
    Dizziness
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Dysarthria
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Dysgeusia
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences all number
    4
    0
    Headache
         subjects affected / exposed
    3 / 44 (6.82%)
    2 / 43 (4.65%)
         occurrences all number
    5
    2
    Memory impairment
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Neuralgia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Neuropathy peripheral
         subjects affected / exposed
    12 / 44 (27.27%)
    5 / 43 (11.63%)
         occurrences all number
    42
    22
    Neurotoxicity
         subjects affected / exposed
    1 / 44 (2.27%)
    3 / 43 (6.98%)
         occurrences all number
    1
    8
    Paraesthesia
         subjects affected / exposed
    3 / 44 (6.82%)
    0 / 43 (0.00%)
         occurrences all number
    6
    0
    Retinal migraine
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Sciatica
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    4
    Speech disorder
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Tremor
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    2
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    18 / 44 (40.91%)
    16 / 43 (37.21%)
         occurrences all number
    48
    55
    Febrile neutropenia
         subjects affected / exposed
    5 / 44 (11.36%)
    0 / 43 (0.00%)
         occurrences all number
    6
    0
    Leukopenia
         subjects affected / exposed
    3 / 44 (6.82%)
    1 / 43 (2.33%)
         occurrences all number
    4
    1
    Lymphopenia
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 43 (6.98%)
         occurrences all number
    7
    7
    Neutropenia
         subjects affected / exposed
    14 / 44 (31.82%)
    8 / 43 (18.60%)
         occurrences all number
    39
    17
    Thrombocytopenia
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences all number
    6
    0
    Thrombotic microangiopathy
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Strabismus
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Vision blurred
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Visual impairment
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal distension
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    2
    Abdominal hernia
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Abdominal pain
         subjects affected / exposed
    14 / 44 (31.82%)
    14 / 43 (32.56%)
         occurrences all number
    28
    31
    Abdominal pain lower
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    7 / 44 (15.91%)
    3 / 43 (6.98%)
         occurrences all number
    10
    4
    Anal inflammation
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Ascites
         subjects affected / exposed
    0 / 44 (0.00%)
    3 / 43 (6.98%)
         occurrences all number
    0
    3
    Constipation
         subjects affected / exposed
    12 / 44 (27.27%)
    12 / 43 (27.91%)
         occurrences all number
    20
    25
    Diarrhoea
         subjects affected / exposed
    35 / 44 (79.55%)
    25 / 43 (58.14%)
         occurrences all number
    137
    72
    Dry mouth
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Dyspepsia
         subjects affected / exposed
    2 / 44 (4.55%)
    2 / 43 (4.65%)
         occurrences all number
    4
    3
    Dysphagia
         subjects affected / exposed
    8 / 44 (18.18%)
    6 / 43 (13.95%)
         occurrences all number
    21
    8
    Enterocolitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Gastric perforation
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Gastrointestinal disorder
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    3 / 44 (6.82%)
    3 / 43 (6.98%)
         occurrences all number
    5
    8
    Haematemesis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    2
    Haemorrhoids
         subjects affected / exposed
    4 / 44 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    9
    0
    Inguinal hernia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Intestinal obstruction
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences all number
    1
    1
    Melaena
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences all number
    3
    0
    Nausea
         subjects affected / exposed
    23 / 44 (52.27%)
    25 / 43 (58.14%)
         occurrences all number
    80
    99
    Oesophageal pain
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences all number
    1
    1
    Oesophageal stenosis
         subjects affected / exposed
    2 / 44 (4.55%)
    1 / 43 (2.33%)
         occurrences all number
    3
    2
    Rectal haemorrhage
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Retroperitoneal haematoma
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Salivary hypersecretion
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Subileus
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    20 / 44 (45.45%)
    16 / 43 (37.21%)
         occurrences all number
    34
    43
    Hepatobiliary disorders
    Cholangitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Cholestasis
         subjects affected / exposed
    2 / 44 (4.55%)
    2 / 43 (4.65%)
         occurrences all number
    2
    4
    Hepatic cytolysis
         subjects affected / exposed
    4 / 44 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    11
    0
    Hepatic pain
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences all number
    1
    1
    Hepatomegaly
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    15 / 44 (34.09%)
    4 / 43 (9.30%)
         occurrences all number
    55
    22
    Dry skin
         subjects affected / exposed
    3 / 44 (6.82%)
    0 / 43 (0.00%)
         occurrences all number
    3
    0
    Erythema
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Hyperkeratosis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Mucocutaneous rash
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Pruritus
         subjects affected / exposed
    4 / 44 (9.09%)
    0 / 43 (0.00%)
         occurrences all number
    8
    0
    Rash
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Rash maculo-papular
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Skin fissures
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    SKIN TOXICITY
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences all number
    1
    2
    Urticaria
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences all number
    1
    1
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences all number
    1
    2
    Dysuria
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Oliguria
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Pollakiuria
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Renal failure
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Urinary tract disorder
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Amyotrophy
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Arthralgia
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Back pain
         subjects affected / exposed
    3 / 44 (6.82%)
    7 / 43 (16.28%)
         occurrences all number
    4
    9
    Bone pain
         subjects affected / exposed
    2 / 44 (4.55%)
    2 / 43 (4.65%)
         occurrences all number
    5
    3
    Muscle spasms
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences all number
    4
    0
    Spinal pain
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences all number
    1
    1
    Tumour pain
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Infections and infestations
    Catheter site infection
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    COVID-19
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Diverticulitis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Folliculitis
         subjects affected / exposed
    3 / 44 (6.82%)
    0 / 43 (0.00%)
         occurrences all number
    5
    0
    Fungal infection
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Gastroenteritis
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Groin infection
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Oral candidiasis
         subjects affected / exposed
    2 / 44 (4.55%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Oral herpes
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Sepsis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences all number
    1
    2
    Urosepsis
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Viral infection
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    1
    Nerve injury
         subjects affected / exposed
    0 / 44 (0.00%)
    1 / 43 (2.33%)
         occurrences all number
    0
    2
    Metabolism and nutrition disorders
    Cell death
         subjects affected / exposed
    3 / 44 (6.82%)
    1 / 43 (2.33%)
         occurrences all number
    7
    1
    Decreased appetite
         subjects affected / exposed
    16 / 44 (36.36%)
    16 / 43 (37.21%)
         occurrences all number
    36
    29
    Dehydration
         subjects affected / exposed
    2 / 44 (4.55%)
    1 / 43 (2.33%)
         occurrences all number
    2
    1
    Diabetes mellitus
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    2
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 44 (0.00%)
    2 / 43 (4.65%)
         occurrences all number
    0
    3
    Hypoalbuminaemia
         subjects affected / exposed
    4 / 44 (9.09%)
    1 / 43 (2.33%)
         occurrences all number
    5
    1
    Hypokalaemia
         subjects affected / exposed
    3 / 44 (6.82%)
    2 / 43 (4.65%)
         occurrences all number
    3
    2
    Hyponatraemia
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences all number
    2
    1
    Hypophosphataemia
         subjects affected / exposed
    1 / 44 (2.27%)
    0 / 43 (0.00%)
         occurrences all number
    1
    0
    Hypoproteinaemia
         subjects affected / exposed
    1 / 44 (2.27%)
    1 / 43 (2.33%)
         occurrences all number
    1
    1
    Malnutrition
         subjects affected / exposed
    0 / 44 (0.00%)
    3 / 43 (6.98%)
         occurrences all number
    0
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    20 Mar 2020
    -Some exemple are given to illustrate the inclusion critéria #4 (Asymptomatic primary tumour (e.g. no dysphagia leading to trouble swallowing tablets, no bleeding requiring repeated blood transfusion) -Clarification regarding the previous lines of treatment for the inclusion criterion #7 (Disease progression after a first line fluoropyrimidine and platinum agent-based chemotherapy or early recurrent disease after surgery with neo-adjuvant and/or adjuvant platinum-based chemotherapy (within 6 months of the end of chemotherapy) or progression during neo-adjuvant and/or adjuvant platinum-based chemotherapy (5-FU or 5-FU prodrugs combined with cisplatin or oxaliplatin). For example, docetaxel combined with FOLFOX, PD-L1/PD1 inhibitors combined with FOLFOX or LV5-FU2-cisplatin or 5-FU-cisplatin are acceptable prior therapies.) -Modification of the inclusion criterion #10 (Lipase ≤1.5 x ULN) -Precision of the non-inclusion criteria #27 (Participation in another clinical trial with investigational product within the 30 days before inclusion) -Modification of the investigators list -Declaration of new recruitment centers -Modification (by Bayer) of the regorafenib IB (safety) -Modification of the patient informed consent following diffusion the new regorafenib IB
    15 Oct 2021
    -End of inclusion of new patients -Regorafenib was removed from the treatment regimen of the last 3 patients in the REGIRI arm

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

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

    European Medicines Agency © 1995-Tue Apr 30 08:41:43 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA