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    Clinical Trial Results:
    Open-label Phase 2 study evaluating efficacy and safety of SAR566658 treatment in patients with CA6 positive metastatic Triple Negative Breast Cancer

    Summary
    EudraCT number
    2016-001962-27
    Trial protocol
    NL   BE   ES   FR   CZ  
    Global end of trial date
    07 Sep 2018

    Results information
    Results version number
    v1(current)
    This version publication date
    25 Aug 2019
    First version publication date
    25 Aug 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ACT14884
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02984683
    WHO universal trial number (UTN)
    U1111-1182-7044
    Sponsors
    Sponsor organisation name
    Sanofi aventis recherche & développement
    Sponsor organisation address
    1 Avenue Pierre Brossolette, Chilly Mazarin, France, 91385
    Public contact
    Trial Transparency Team, Sanofi aventis recherche & développement, contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi aventis recherche & développement, contact-US@sanofi.com
    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
    05 Nov 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Sep 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate the tumour Objective Response Rate (ORR), according to the Response Evaluation Criteria in Solid Tumours (RECIST 1.1) of SAR566658 in subjects with CA6-positive metastatic triple negative breast cancer (TNBC). Part 1: To select the SAR566658 dose based on ORR and safety of 2 dose levels of SAR566658 in subjects with metastatic TNBC overexpressing CA6 (membrane intensity of 2+, 3+ in >=30 percent(%) of tumour cells). Part 2: -Part 2a: To demonstrate the activity of SAR566658 based on ORR in subjects with metastatic TNBC overexpressing CA6 (membrane intensity of 2+, 3+ in >=30% of tumour cells) treated at the selected dose in an expanded cohort, in addition to the subjects treated in Part 1, - Part 2b: To assess the efficacy of SAR566658 based on ORR in subjects with metastatic TNBC and mild CA6 expression (with at least 1% positive tumour cells at intensity >=1+ and <30% of tumour cells at intensity of 2+, 3+) treated at the selected dose in “mild CA6 expression cohort”.
    Protection of trial subjects
    Subjects were fully informed of all pertinent aspects of the clinical trial as well as the possibility to discontinue at any time in language and terms appropriate for the subject and considering the local culture. During the course of the trial, subjects were provided with individual subject cards indicating the nature of the trial the subject was participating, contact details and any information needed in the event of a medical emergency. Collected personal data and human biological samples were processed in compliance with the Sanofi-Aventis Group Personal Data Protection Charter ensuring that the Group abides by the laws governing personal data protection in force in all countries in which it operates.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    23 Mar 2017
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Italy: 3
    Country: Number of subjects enrolled
    Netherlands: 3
    Country: Number of subjects enrolled
    Spain: 14
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    Czech Republic: 1
    Worldwide total number of subjects
    23
    EEA total number of subjects
    23
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    19
    From 65 to 84 years
    4
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted at 13 sites in 5 countries from 23 March 2017 to 07 September 2018.

    Pre-assignment
    Screening details
    A total of 23 subjects who met all of the inclusion criteria and none of the exclusion criteria were enrolled in the study and included in Part 1. The study was prematurely terminated due to safety reasons, hence Part 2 was not conducted and no analysis was performed.

    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
    SAR566658 90 mg/m^2
    Arm description
    Subjects received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
    Arm type
    Experimental

    Investigational medicinal product name
    SAR566658
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    SAR566658 90 mg/m^2, intravenous infusion on Day 1 and 8 of each 21-day treatment cycle.

    Arm title
    SAR566658 120 mg/m^2
    Arm description
    Subjects received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).
    Arm type
    Experimental

    Investigational medicinal product name
    SAR566658
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    SAR566658 120 mg/m^2, intravenous infusion on Day 1 and 8 of each 21-day treatment cycle.

    Number of subjects in period 1
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2
    Started
    11
    12
    Completed
    0
    0
    Not completed
    11
    12
         Adverse event
    3
    3
         Withdrawal by subject
    1
    -
         Disease progression
    7
    9

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    SAR566658 90 mg/m^2
    Reporting group description
    Subjects received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).

    Reporting group title
    SAR566658 120 mg/m^2
    Reporting group description
    Subjects received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).

    Reporting group values
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2 Total
    Number of subjects
    11 12 23
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    56.73 ± 11.23 50.33 ± 15.30 -
    Gender categorical
    Units: Subjects
        Female
    11 12 23
        Male
    0 0 0
    Race
    Units: Subjects
        American Indian or Alaska Native
    0 0 0
        White
    11 12 23
        Black or African american
    0 0 0
        Asian
    0 0 0
        Native Hawaiian or other Pacific Island
    0 0 0
        Not reported
    0 0 0
        Unknown
    0 0 0

    End points

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    End points reporting groups
    Reporting group title
    SAR566658 90 mg/m^2
    Reporting group description
    Subjects received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).

    Reporting group title
    SAR566658 120 mg/m^2
    Reporting group description
    Subjects received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).

    Primary: Number of Subjects With Investigational Medicinal Product (IMP)-Related Predefined Safety Criteria Findings

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    End point title
    Number of Subjects With Investigational Medicinal Product (IMP)-Related Predefined Safety Criteria Findings [1]
    End point description
    Predefined safety criteria was defined as occurrence of any following IMP-related treatment emergent adverse event (TEAE) (based on National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v4.03): Grade >=3 TEAE from the System Organ Class (SOC) of eye disorders, Grade >=3 peripheral neuropathy (Preferred Term), Grade >=4 TEAE. Only those categories in which at least 1 subject had data were reported. Per NCI-CTCAE v4.03, Adverse Events (AE) were graded as follows: Grade 1: Mild; asymptomatic/mild symptoms; Grade 2: Moderate; minimal, local or non-invasive intervention indicated; Grade 3: Severe or medically significant; hospitalization or prolongation of hospitalization indicated; Grade 4: Life-threatening consequences; Grade 5: Death related to AE. Analysis was performed on evaluable for predefined safety criteria population which included subjects treated in the study and had completed 2 cycles, or who experienced predefined safety criteria.
    End point type
    Primary
    End point timeframe
    Up to Cycle 2 (each cycle of 21 days)
    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: As the endpoint is descriptive in nature, hence no statistical analysis was provided.
    End point values
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2
    Number of subjects analysed
    9
    9
    Units: Subjects
    number (not applicable)
        Grade>=3 related TEAE from SOC Eye disorders
    2
    2
    No statistical analyses for this end point

    Primary: Percentage of Subjects With Objective Response

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    End point title
    Percentage of Subjects With Objective Response [2]
    End point description
    Objective Response in subjects was defined as the subjects with complete response (CR) and partial response (PR) as best response according to RECIST 1.1. As per RECIST 1.1, CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). PR was defined was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Analysis was performed on all-treated population which included subjects who actually received at least 1 dose or any partial dose of SAR566658.
    End point type
    Primary
    End point timeframe
    From Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: As the endpoint is descriptive in nature, hence no statistical analysis was provided.
    End point values
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2
    Number of subjects analysed
    11
    12
    Units: percentage of subjects
        number (confidence interval 80%)
    9.1 (1.0 to 31.0)
    8.3 (0.9 to 28.7)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With Disease Control

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    End point title
    Percentage of Subjects With Disease Control
    End point description
    Disease control in subjects was defined as the subjects with CR, PR and stable disease (SD) with a duration of at least 3 months. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum diameters while on study. Data for this endpoint was not collected and analysed due to early termination of the study.
    End point type
    Secondary
    End point timeframe
    From Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
    End point values
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2
    Number of subjects analysed
    0 [3]
    0 [4]
    Units: percentage of subjects
        number (not applicable)
    Notes
    [3] - Data was not collected and analysed due to early termination of the study.
    [4] - Data was not collected and analysed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Duration of response (DOR)

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    End point title
    Duration of response (DOR)
    End point description
    DOR was defined as the time from the first documentation of objective tumour response (CR or PR) to the first radiological documentation of tumour progression or death (due to any cause), whichever comes first. As per RECIST 1.1, CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive disease was defined as at least a 20% increase in the sum of diameters of target lesions. Data for this endpoint was not collected and analysed due to early termination of the study.
    End point type
    Secondary
    End point timeframe
    From Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
    End point values
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2
    Number of subjects analysed
    0 [5]
    0 [6]
    Units: days
        number (not applicable)
    Notes
    [5] - Data was not collected and analysed due to early termination of the study.
    [6] - Data was not collected and analysed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Progression free survival (PFS)

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    End point title
    Progression free survival (PFS)
    End point description
    PFS was defined as the time interval between the date of first study treatment administration and the date of documented tumour progression or death (due to any cause), whichever comes first. As per RECIST 1.1, Progression was defined as at least a 20% increase in the sum of diameters of target lesions. Data for this endpoint was not collected and analysed due to early termination of the study.
    End point type
    Secondary
    End point timeframe
    From Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
    End point values
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2
    Number of subjects analysed
    0 [7]
    0 [8]
    Units: days
        number (not applicable)
    Notes
    [7] - Data was not collected and analysed due to early termination of the study.
    [8] - Data was not collected and analysed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Time to Tumour progression (TTP)

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    End point title
    Time to Tumour progression (TTP)
    End point description
    TTP was defined as the time interval between the date of first study treatment administration and the date of the first radiologically documented tumour progression. As per RECIST 1.1, progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. Data for this endpoint was not collected and analysed due to early termination of the study.
    End point type
    Secondary
    End point timeframe
    From Baseline, every 6 weeks until radiological disease progression or study cut-off, whichever comes first (maximum number of cycles was 3, each cycle 21 days)
    End point values
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2
    Number of subjects analysed
    0 [9]
    0 [10]
    Units: days
        number (not applicable)
    Notes
    [9] - Data was not collected and analysed due to early termination of the study.
    [10] - Data was not collected and analysed due to early termination of the study.
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment Emergent Adverse Events and Serious Adverse Events (SAE)

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    End point title
    Number of Subjects With Treatment Emergent Adverse Events and Serious Adverse Events (SAE)
    End point description
    AE was defined as any untoward medical occurrence in a subject who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened in grade or became serious during the on-treatment period (the time from the first treatment administration to the last treatment administration +30 days). An SAE is any untoward medical occurrence that at any dose: results in death, Is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect, is a medically important event. Analysis was performed on all treated population.
    End point type
    Secondary
    End point timeframe
    Up to 30 days after last drug administration
    End point values
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2
    Number of subjects analysed
    11
    12
    Units: subjects
    number (not applicable)
        Any TEAE
    11
    12
        Any treatment emergent SAE
    1
    6
        Any TEAE leading to treatment discontinuation
    3
    3
    No statistical analyses for this end point

    Secondary: Number of Subjects with Keratopathies (corneal toxicity)

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    End point title
    Number of Subjects with Keratopathies (corneal toxicity)
    End point description
    Keratopathy is an eye disorder that involves a blister-like swelling of the cornea (the clear layer in front of the iris and pupil). All subjects received ocular primary prophylaxis in each eye in order to prevent the occurrence of keratopathies at the time of each infusion (vasoconstrictor, ophthalmic topical steroid, and cold mask on eyes) and steroid eye drops for an additional 2 days following SAR566658 administration. Analysis was performed on all treated population.
    End point type
    Secondary
    End point timeframe
    Up to 30 days after last drug administration
    End point values
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2
    Number of subjects analysed
    11
    12
    Units: subjects
    number (not applicable)
        Keratopathy: All Grade
    3
    5
    No statistical analyses for this end point

    Secondary: Number of Subjects with Positive Anti-SAR566658 Antibodies Response

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    End point title
    Number of Subjects with Positive Anti-SAR566658 Antibodies Response
    End point description
    Data for this endpoint was not collected and analysed due to early termination of the study.
    End point type
    Secondary
    End point timeframe
    Up to 3 treatment cycles, each cycle 21 days
    End point values
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2
    Number of subjects analysed
    0 [11]
    0 [12]
    Units: subjects
        number (not applicable)
    Notes
    [11] - Data was not collected and analysed due to early termination of the study.
    [12] - Data was not collected and analysed due to early termination of the study.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse event (AE) data was collected from the baseline up to 3 treatment cycles, each cycle 21 days.
    Adverse event reporting additional description
    Reported AEs are treatment-emergent adverse events i.e. AEs that developed/worsened during ‘treatment period’(time from the first treatment administration to the last treatment administration + 30 days). Analysis was performed on safety population which included all subjects who received at least 1 dose (or any partial) of SAR566658.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    21.0
    Reporting groups
    Reporting group title
    SAR566658 90 mg/m^2
    Reporting group description
    Subjects received SAR566658 90 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).

    Reporting group title
    SAR566658 120 mg/m^2
    Reporting group description
    Subjects received SAR566658 120 mg/m^2 as intravenous infusion on Day 1 and Day 8 of each 21-day treatment cycle (maximum number of cycles received was 3).

    Serious adverse events
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 11 (9.09%)
    6 / 12 (50.00%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Injury, poisoning and procedural complications
    Ankle Fracture
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases To Meninges
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis Acute
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypercalcaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory Tract Infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal Bacteraemia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    SAR566658 90 mg/m^2 SAR566658 120 mg/m^2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    11 / 11 (100.00%)
    12 / 12 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 11 (36.36%)
    3 / 12 (25.00%)
         occurrences all number
    4
    3
    Device Related Thrombosis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Fatigue
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Hyperthermia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Oedema Peripheral
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Insomnia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Breast Pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Breast Ulceration
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Metrorrhagia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Intentional Overdose
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Investigations
    Blood Bilirubin Increased
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Transaminases Increased
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Weight Decreased
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    2
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    0 / 11 (0.00%)
    3 / 12 (25.00%)
         occurrences all number
    0
    3
    Pleural Effusion
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Pulmonary Toxicity
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Headache
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 12 (8.33%)
         occurrences all number
    1
    2
    Neuropathy Peripheral
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Paraesthesia
         subjects affected / exposed
    2 / 11 (18.18%)
    3 / 12 (25.00%)
         occurrences all number
    2
    3
    Peripheral Sensory Neuropathy
         subjects affected / exposed
    0 / 11 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    2
    Eye disorders
    Abnormal Sensation In Eye
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Corneal Epithelial Microcysts
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Corneal Opacity
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Diplopia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Dry Eye
         subjects affected / exposed
    3 / 11 (27.27%)
    1 / 12 (8.33%)
         occurrences all number
    3
    1
    Halo Vision
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Keratitis
         subjects affected / exposed
    5 / 11 (45.45%)
    1 / 12 (8.33%)
         occurrences all number
    5
    1
    Keratopathy
         subjects affected / exposed
    3 / 11 (27.27%)
    5 / 12 (41.67%)
         occurrences all number
    3
    6
    Periorbital Oedema
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Photophobia
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Vision Blurred
         subjects affected / exposed
    2 / 11 (18.18%)
    1 / 12 (8.33%)
         occurrences all number
    2
    1
    Vitreous Floaters
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Xerophthalmia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Ear and labyrinth disorders
    Ear Pruritus
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal Pain
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Constipation
         subjects affected / exposed
    3 / 11 (27.27%)
    2 / 12 (16.67%)
         occurrences all number
    3
    2
    Diarrhoea
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Dry Mouth
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Dyspepsia
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    1 / 11 (9.09%)
    2 / 12 (16.67%)
         occurrences all number
    1
    2
    Odynophagia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Paraesthesia Oral
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Stomatitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Vomiting
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Onychomadesis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Palmar-Plantar Erythrodysaesthesia Syndrome
         subjects affected / exposed
    2 / 11 (18.18%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Pruritus Generalised
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Rash
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 11 (18.18%)
    2 / 12 (16.67%)
         occurrences all number
    2
    2
    Muscle Spasms
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Myalgia
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Neck Pain
         subjects affected / exposed
    1 / 11 (9.09%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Endocrine disorders
    Cushingoid
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Decreased Appetite
         subjects affected / exposed
    1 / 11 (9.09%)
    3 / 12 (25.00%)
         occurrences all number
    1
    3
    Infections and infestations
    Cystitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Folliculitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Gastrointestinal Infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Periodontitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Sinusitis
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Skin Infection
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Tonsillitis
         subjects affected / exposed
    1 / 11 (9.09%)
    0 / 12 (0.00%)
         occurrences all number
    1
    0
    Urinary Tract Infection
         subjects affected / exposed
    0 / 11 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    07 Sep 2018
    Analysis after the first 20 subjects had been enrolled revealed a higher than expected rate of non-serious ophthalmic TEAEs identified as keratitis and keratopathy leading to dose modification and/or treatment discontinuation in both the 90 mg/m^2 and 120 mg/m^2 treatment groups which is not outweighed by a significant clinical benefit with SAR566658 and led to decision to prematurely stop the study. The corneal prophylaxis administered to all subjects does not show a positive impact on incidence of the events. The preliminary efficacy analysis indicated that the ORR was not likely to support the continuation of the study.
    -

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study was prematurely terminated due to safety reasons, hence Part 2 was not conducted and no analysis was performed.
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