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    Clinical Trial Results:
    Multiorgan Metabolic imaging response assessment of Abemaciclib: the MiMe-A trial

    Summary
    EudraCT number
    		 2017-000123-28
    Trial protocol
    		 BE   FR  
    Global end of trial date
    20 Dec 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Nov 2024
    First version publication date
    09 Nov 2024
    Other versions
    Summary report(s)
    		 Final Study Report

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    IJB-MULTI-MIME-A-2017
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03339843
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Institut Jules Bordet
    Sponsor organisation address
    rue Meyelemeersch 90, Anderlecht, Belgium, 1070
    Public contact
    CTSU, Institut Jules Bordet, ctsu.trials@bordet.be
    Scientific contact
    CTSU, Institut Jules Bordet, ctsu.trials@bordet.be
    Sponsor organisation name
    Institut Jules Bordet
    Sponsor organisation address
    Rue Meylemeersch 90, Anderlecht, Belgium, 1070
    Public contact
    Dr. Laura Polastro , Institut Jules Bordet, laura.polastro@hubruxelles.be
    Scientific contact
    Dr Alain Hendlisz, Institut Jules Bordet, alain.hendlisz@hubruxelles.be
    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
    21 Nov 2023
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    12 Nov 2021
    Global end of trial reached?
    Yes
    Global end of trial date
    20 Dec 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the anti-tumour activity of abemaciclib in the five tumour types studied in this trial using the combination of FDG-PET/CT during the first cycle of therapy (early FDG- PET/CT) and RECIST v1.1 after 2 cycles of therapy as a screening tool.
    Protection of trial subjects
    Both dose suppression (within a cycle) and cycle delay are permitted in case of clinically significant toxicities. Abemaciclib may be held up to 14 days within a cycle or at the start of next cycle to permit sufficient time recovery from the toxicity. If a dose suspension occurs, the investigator may resume abemaciclib dosing at the same dose level for the remainder of the cycle or at reduced dose (assuming resolution to at least grade 1 for the non-hematological and at least grade 2 for hematological toxicity). If the subject experiences the same toxicity with the same or greater severity requiring a dose suspension within a cycle or at start of the next cycle, the subject must be dose reduced and non rechallenged a second time at the prior dose level. Subject not recovering from toxicity within 14 days should be considered for discontinuation of abemaciclib. In exceptional circumstances, a delay > 14 days is permitted upon agreement of the Investigator and the Sponsor. Subjects who were taking strong CYP3A inhibitors were recommended to reduce the abemaciclib dose. Very close monitoring of side effects was organized (for example medical visit after 10 days of taking abemaciclib) in order to adapt supportive treatments and doses of abemaciclib in the event of side effects.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Oct 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy
    Long term follow-up duration
    		 18 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Belgium: 62
    Country: Number of subjects enrolled
    France: 23
    Worldwide total number of subjects
    85
    EEA total number of subjects
    85
    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)
    26
    From 65 to 84 years
    57
    85 years and over
    2

    Subject disposition

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    Recruitment
    Recruitment details
    		 Planned recruitment period : 24 months The recruitment of a tumour cohort will be stopped when at least 13 evaluable patients have been enrolled in the cohort and have been treated until the first RECIST assessment (ie: after 2 cycles).

    Pre-assignment
    Screening details
    		 During the screening period, following signature of the Informed Consent Form and registration, the principal investigator confirms the subject’s eligibility for the study by conducting the assessments described below and complete the corresponding CRF.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Cohort 1: Esophaegal adenocarcinoma
    Arm description
    		 Subjects with histologically confirmed esophageal adenocarcinoma that is metastatic or unresectable and for which standard platinum regimens are no longer effective.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Abemaciclib will be continuously administrated orally at a dose of 150mg twice daily until disease progression, until new lesions are observed at the early FDG-PET/CT, until the lack of tolerability or the subject ‘s consent withdrawal. One cycle is 28 days.

    Arm title
    		 Cohort 2: Esophageal squamous cell carcinoma
    Arm description
    		 Subjects with histologically confirmed esophageal squamous cell carcinoma that is metastatic or unresectable and for which standard platinum regimens are no longer effective.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Abemaciclib will be continuously administrated orally at a dose of 150mg twice daily until disease progression, until new lesions are observed at the early FDG-PET/CT, until the lack of tolerability or the subject ‘s consent withdrawal. One cycle is 28 days.

    Arm title
    		 Cohort 3: Cholangiocarcinoma
    Arm description
    		 Subjects with histologically confirmed cholangiocarcinoma that is metastatic or unresectable and for which standard platinum regimens are no longer effective.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Abemaciclib will be continuously administrated orally at a dose of 150mg twice daily until disease progression, until new lesions are observed at the early FDG-PET/CT, until the lack of tolerability or the subject ‘s consent withdrawal. One cycle is 28 days.

    Arm title
    		 Cohort 4: Urothelial cancer
    Arm description
    		 Subjects with histologically confirmed urothelial cancer that is metastatic or unresectable and for which standard platinum regimens are no longer effective. Subjects must have been pre-treated with nivolumab or another immune checkpoint inhibitor.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Abemaciclib will be continuously administrated orally at a dose of 150mg twice daily until disease progression, until new lesions are observed at the early FDG-PET/CT, until the lack of tolerability or the subject ‘s consent withdrawal. One cycle is 28 days.

    Arm title
    		 Cohort 5: Endometrial cancer
    Arm description
    		 Subjects with histologically confirmed endometrial cancer a that is metastatic or unresectable and for which standard platinum regimens are no longer effective.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Abemaciclib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Abemaciclib will be continuously administrated orally at a dose of 150mg twice daily until disease progression, until new lesions are observed at the early FDG-PET/CT, until the lack of tolerability or the subject ‘s consent withdrawal. One cycle is 28 days.

    Number of subjects in period 1
    		Cohort 1: Esophaegal adenocarcinoma Cohort 2: Esophageal squamous cell carcinoma Cohort 3: Cholangiocarcinoma Cohort 4: Urothelial cancer Cohort 5: Endometrial cancer
    Started
    17
    17
    17
    17
    17
    Completed
    17
    17
    17
    17
    17

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: Esophaegal adenocarcinoma
    Reporting group description
    		 Subjects with histologically confirmed esophageal adenocarcinoma that is metastatic or unresectable and for which standard platinum regimens are no longer effective.

    Reporting group title
    Cohort 2: Esophageal squamous cell carcinoma
    Reporting group description
    		 Subjects with histologically confirmed esophageal squamous cell carcinoma that is metastatic or unresectable and for which standard platinum regimens are no longer effective.

    Reporting group title
    Cohort 3: Cholangiocarcinoma
    Reporting group description
    		 Subjects with histologically confirmed cholangiocarcinoma that is metastatic or unresectable and for which standard platinum regimens are no longer effective.

    Reporting group title
    Cohort 4: Urothelial cancer
    Reporting group description
    		 Subjects with histologically confirmed urothelial cancer that is metastatic or unresectable and for which standard platinum regimens are no longer effective. Subjects must have been pre-treated with nivolumab or another immune checkpoint inhibitor.

    Reporting group title
    Cohort 5: Endometrial cancer
    Reporting group description
    		 Subjects with histologically confirmed endometrial cancer a that is metastatic or unresectable and for which standard platinum regimens are no longer effective.

    Reporting group values
    		 Cohort 1: Esophaegal adenocarcinoma Cohort 2: Esophageal squamous cell carcinoma Cohort 3: Cholangiocarcinoma Cohort 4: Urothelial cancer Cohort 5: Endometrial cancer Total
    Number of subjects
    		 17 17 17 17 17 85
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0 0
        Adults (18-64 years)
    		 8 5 3 5 5 26
        From 65-84 years
    		 9 12 12 12 12 57
        85 years and over
    		 0 0 2 0 0 2
    Gender categorical
    Units: Subjects
        Female
    		 3 6 11 2 17 39
        Male
    		 14 11 6 15 0 46

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: Esophaegal adenocarcinoma
    Reporting group description
    		 Subjects with histologically confirmed esophageal adenocarcinoma that is metastatic or unresectable and for which standard platinum regimens are no longer effective.

    Reporting group title
    Cohort 2: Esophageal squamous cell carcinoma
    Reporting group description
    		 Subjects with histologically confirmed esophageal squamous cell carcinoma that is metastatic or unresectable and for which standard platinum regimens are no longer effective.

    Reporting group title
    Cohort 3: Cholangiocarcinoma
    Reporting group description
    		 Subjects with histologically confirmed cholangiocarcinoma that is metastatic or unresectable and for which standard platinum regimens are no longer effective.

    Reporting group title
    Cohort 4: Urothelial cancer
    Reporting group description
    		 Subjects with histologically confirmed urothelial cancer that is metastatic or unresectable and for which standard platinum regimens are no longer effective. Subjects must have been pre-treated with nivolumab or another immune checkpoint inhibitor.

    Reporting group title
    Cohort 5: Endometrial cancer
    Reporting group description
    		 Subjects with histologically confirmed endometrial cancer a that is metastatic or unresectable and for which standard platinum regimens are no longer effective.

    Primary: Overall Response (combining PERCIST and RECIST evaluations)

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    End point title
    		 Overall Response (combining PERCIST and RECIST evaluations) [1]
    End point description
    Based on the protocol, a subject is considered evaluable if he/she has a clear treatment success or non-treatment success. Treatment success is defined as when a subject has metabolic response according to PERCIST with a response cut off set at 15% at the early FDG-PET/CT and a morphological disease control after 2 cycles measured by RECIST v1.1 (disease control is defined as complete response (CR), partial response (PR) or stable disease (SD)).
    End point type
    Primary
    End point timeframe
    after 2 cycles
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The analysis will be done on eligible and evaluable patients. The thresholds to go on after the interim analysis have been described above. In case, accrual goes beyond the first step, statistical testing will be done using a chi square test (at 10% one-sided significance level). A 95% confidence interval will also be reported using an exact binomial distribution.
    End point values
    		 Cohort 1: Esophaegal adenocarcinoma Cohort 2: Esophageal squamous cell carcinoma Cohort 3: Cholangiocarcinoma Cohort 4: Urothelial cancer Cohort 5: Endometrial cancer
    Number of subjects analysed
    17
    17
    17
    17
    17
    Units: Number
        Treatment Success
    0
    0
    0
    1
    0
        Treatment Failure
    17
    17
    17
    16
    17
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Non-serious adverse events (AEs) : from first administration of abemaciclib until 28 days after the last administration of abemaciclib Serious adverse events (SAEs) : from CF signature until initiation of abemaciclib
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.1
    Reporting groups
    Reporting group title
    Cohort 1: Esophaegal adenocarcinoma
    Reporting group description
    		 Subjects with histologically confirmed esophageal adenocarcinoma that is metastatic or unresectable and for which standard platinum regimens are no longer effective.

    Reporting group title
    Cohort 2: Esophageal squamous cell carcinoma
    Reporting group description
    		 Subjects with histologically confirmed esophageal squamous cell carcinoma that is metastatic or unresectable and for which standard platinum regimens are no longer effective.

    Reporting group title
    Cohort 3: Cholangiocarcinoma
    Reporting group description
    		 Subjects with histologically confirmed cholangiocarcinoma that is metastatic or unresectable and for which standard platinum regimens are no longer effective.

    Reporting group title
    Cohort 4: Urothelial cancer
    Reporting group description
    		 Subjects with histologically confirmed urothelial cancer that is metastatic or unresectable and for which standard platinum regimens are no longer effective. Subjects must have been pre-treated with nivolumab or another immune checkpoint inhibitor.

    Reporting group title
    Cohort 5: Endometrial cancer
    Reporting group description
    		 Subjects with histologically confirmed endometrial cancer a that is metastatic or unresectable and for which standard platinum regimens are no longer effective.

    Serious adverse events
    		 Cohort 1: Esophaegal adenocarcinoma Cohort 2: Esophageal squamous cell carcinoma Cohort 3: Cholangiocarcinoma Cohort 4: Urothelial cancer Cohort 5: Endometrial cancer
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 17 (17.65%)
    4 / 17 (23.53%)
    6 / 17 (35.29%)
    6 / 17 (35.29%)
    3 / 17 (17.65%)
         number of deaths (all causes)
    1
    2
    1
    1
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Ureteric anastomosis complication
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Bezoar
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    1 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    2 / 17 (11.76%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    2 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pulmonary sepsis
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Biliary sepsis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diabetic metabolic decompensation
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Cohort 1: Esophaegal adenocarcinoma Cohort 2: Esophageal squamous cell carcinoma Cohort 3: Cholangiocarcinoma Cohort 4: Urothelial cancer Cohort 5: Endometrial cancer
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 17 (82.35%)
    6 / 17 (35.29%)
    17 / 17 (100.00%)
    16 / 17 (94.12%)
    16 / 17 (94.12%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Pallor
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Pelvic venous thrombosis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Superficial vein thrombosis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    11 / 17 (64.71%)
    5 / 17 (29.41%)
    8 / 17 (47.06%)
    4 / 17 (23.53%)
    8 / 17 (47.06%)
         occurrences all number
    12
    5
    8
    4
    8
    chest pain
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    Malaise
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    4 / 17 (23.53%)
         occurrences all number
    0
    0
    1
    0
    4
    Oedema
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Mucosal inflammation
         subjects affected / exposed
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    2
    0
    0
    1
    General physical health deterioration
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Inflammation
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    2 / 17 (11.76%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    2
    1
    0
    Influenza like illness
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    1
    2
    0
    Pain
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Immune system disorders
    Pneumonia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    1
    1
    Hypersensitivity
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Reproductive system and breast disorders
    Prostatism
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 17 (5.88%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    3 / 17 (17.65%)
         occurrences all number
    1
    2
    0
    2
    3
    Epistaxis
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    2
    0
    Dyspnoea
         subjects affected / exposed
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    2 / 17 (11.76%)
    4 / 17 (23.53%)
    2 / 17 (11.76%)
         occurrences all number
    0
    2
    2
    5
    3
    Pulmonary embolism
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Nasal dryness
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Haemoptysis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Bronchopneumopathy
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Lung disorder
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Productive cough
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Insomnia
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    0
    2
    1
    Confusional state
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Depression
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    1
    0
    1
    Nervousness
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Investigations
    Blood creatine increased
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 17 (5.88%)
    2 / 17 (11.76%)
    1 / 17 (5.88%)
    6 / 17 (35.29%)
    4 / 17 (23.53%)
         occurrences all number
    1
    2
    2
    7
    4
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    1
    1
    Weight decreased
         subjects affected / exposed
    2 / 17 (11.76%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    3 / 17 (17.65%)
         occurrences all number
    2
    1
    1
    0
    3
    White blood cell count decreased
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    3 / 17 (17.65%)
         occurrences all number
    0
    0
    1
    2
    3
    Bilirubin conjugated increased
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Injury, poisoning and procedural complications
    Upper limb fracture
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Fall
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Congenital, familial and genetic disorders
    Tracheo-oesophageal fistula
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Palpitations
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Arteriospasm coronary
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Tachycardia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Nervous system disorders
    Disturbance in attention
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Dizziness
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    1
    1
    Headache
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    3 / 17 (17.65%)
    1 / 17 (5.88%)
         occurrences all number
    1
    0
    1
    3
    1
    Dysgeusia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    2 / 17 (11.76%)
    3 / 17 (17.65%)
         occurrences all number
    0
    1
    1
    3
    4
    Tremor
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    0
    1
    Monoparesis
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Altered state of consciousness
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Blood and lymphatic system disorders
    Leukopenia
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    1
    0
    Neutropenia
         subjects affected / exposed
    1 / 17 (5.88%)
    2 / 17 (11.76%)
    4 / 17 (23.53%)
    3 / 17 (17.65%)
    4 / 17 (23.53%)
         occurrences all number
    1
    2
    6
    4
    4
    Lymphopenia
         subjects affected / exposed
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Thrombocytopenia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    6 / 17 (35.29%)
    3 / 17 (17.65%)
    4 / 17 (23.53%)
         occurrences all number
    0
    1
    9
    4
    6
    Ear and labyrinth disorders
    Tinnitus
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Vertigo
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    2 / 17 (11.76%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    2
    2
    0
    Eye disorders
    Lacrimation increased
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    1
    0
    0
    0
    1
    Xerophthalmia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Gastrointestinal disorders
    Constipation
         subjects affected / exposed
    1 / 17 (5.88%)
    4 / 17 (23.53%)
    4 / 17 (23.53%)
    6 / 17 (35.29%)
    1 / 17 (5.88%)
         occurrences all number
    1
    4
    5
    6
    1
    Abdominal distension
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Abdominal pain
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    3 / 17 (17.65%)
    1 / 17 (5.88%)
    7 / 17 (41.18%)
         occurrences all number
    0
    1
    3
    2
    7
    Anal haemorrhage
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 17 (0.00%)
    3 / 17 (17.65%)
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
         occurrences all number
    0
    3
    0
    2
    0
    Abdominal rigidity
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Dry mouth
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    1
    0
    0
    0
    1
    Dyspepsia
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    2 / 17 (11.76%)
         occurrences all number
    1
    1
    0
    1
    2
    Dysphagia
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    1
    0
    0
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    0
    1
    1
    Nausea
         subjects affected / exposed
    5 / 17 (29.41%)
    1 / 17 (5.88%)
    6 / 17 (35.29%)
    7 / 17 (41.18%)
    6 / 17 (35.29%)
         occurrences all number
    5
    1
    6
    10
    6
    Gingival swelling
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Oral pain
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Stomatitis
         subjects affected / exposed
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    1
    1
    0
    0
    1
    Vomiting
         subjects affected / exposed
    4 / 17 (23.53%)
    1 / 17 (5.88%)
    2 / 17 (11.76%)
    8 / 17 (47.06%)
    2 / 17 (11.76%)
         occurrences all number
    4
    1
    2
    10
    2
    Intestinal obstruction
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Flatulence
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Inguinal hernia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hepatobiliary disorders
    Hepatic pain
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Dry skin
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    1
    2
    0
    2
    Dermatitis bullous
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Palmar-plantar erythrodysaesthesia syndrome
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    1
    0
    1
    Pruritus
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    1
    0
    1
    Rash
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
         occurrences all number
    0
    1
    0
    1
    2
    Ingrowing nail
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Skin lesion
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    2 / 17 (11.76%)
    2 / 17 (11.76%)
    1 / 17 (5.88%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
         occurrences all number
    2
    2
    1
    2
    0
    Acute kidney injury
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    1
    2
    Bladder pain
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    Dysuria
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    1
    1
    Chronic kidney disease
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Cystitis haemorrhagic
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Haematuria
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Pollakiuria
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    1
    1
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hypothyroidism
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    1
    1
    0
    Arthralgia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    1
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Musculoskeletal pain
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    2 / 17 (11.76%)
         occurrences all number
    0
    0
    0
    0
    2
    Myalgia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    1
    1
    Arthritis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Infections and infestations
    Cystitis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    2
    Bronchitis
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    Influenza
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Fungal oesophagitis
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Oral herpes
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    0
    1
    Urinary tract infection
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    3 / 17 (17.65%)
    1 / 17 (5.88%)
         occurrences all number
    0
    0
    0
    3
    1
    Biliary tract infection
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    COVID-19
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Cestode infection
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Fungal infection
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Cholangitis infective
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Pyelonephritis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Conjunctivitis
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    2 / 17 (11.76%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    2
    0
    0
    Tooth abscess
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    0
    1
    0
    Vulvovaginal mycotic infection
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    1
    0
    Hypoglycaemia
         subjects affected / exposed
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    1
    0
    0
    0
    0
    Malnutrition
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    0
    0
    0
    Hypokalaemia
         subjects affected / exposed
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    3 / 17 (17.65%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    1
    3
    0
    0
    Hypophosphataemia
         subjects affected / exposed
    0 / 17 (0.00%)
    0 / 17 (0.00%)
    1 / 17 (5.88%)
    0 / 17 (0.00%)
    0 / 17 (0.00%)
         occurrences all number
    0
    0
    1
    0
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Dec 2018
    patient information sheet/ informed consent (including addendum)
    19 Feb 2019
    documents related to IMP or IMPD patient informatio sheet/ informed consent included addendum protocol
    22 May 2019
    • Addition of at least a new site or a site whose LEC did not reply initially or moved site
    09 Jul 2019
    • Addition of at least a new site or a site whose LEC did not reply initially or moved site
    12 Sep 2019
    • New/amended IDMC charter • New/amended patient information sheet / informed consent (including addendum) • New/amended protocol • New/amended patient diary
    18 Sep 2019
    • New/amended patient information sheet / informed consent (including addendum) • New/amended patient diary • New/amended protocol
    15 Oct 2019
    • Change of PI - already approved site
    17 Oct 2019
    • New/amended patient information sheet / informed consent (including addendum)
    13 Mar 2020
    • Addition of at least a new site or a site whose LEC did not reply initially or moved site • Change of PI - already approved site
    13 May 2020
    • Changes in the logistics of the trial, which are NOT site-related (e.g. :lab, CRO etc)
    30 Jun 2020
    • Closure of an approved site • Addition of at least a new site or a site whose LEC did not reply initially or moved site
    21 Oct 2020
    Addition of at least a new site or a site whose LEC did not reply initially or moved site

    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.
    An interim analysis was performed on each tumour cohort in the first stage, which includes the first 13 evaluable subjects. Since there were 2 or less subjects with treatment success in these 13 evaluable subjects (futility criteria) in all cohorts,
    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.

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