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    Clinical Trial Results:
    A Phase 1 Study of Eribulin Mesylate, a Novel Microtubule Targeting Chemotherapeutic Agent in Children with Refractory or Recurrent Solid Tumors (Excluding CNS), Including Lymphomas

    Summary
    EudraCT number
    		 2016-001894-34
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    28 Jan 2016

    Results information
    Results version number
    		 v1(current)
    This version publication date
    05 Jul 2018
    First version publication date
    05 Jul 2018
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    E7389-A001-113
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02171260
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Eisai Inc.
    Sponsor organisation address
    155 Tice Boulevard, Woodcliff Lake, United States, 07677
    Public contact
    Eisai Medical Information, Eisai Inc., 1 8882742378, esi_medinfo@eisai.com
    Scientific contact
    Eisai Medical Information, Eisai Inc., 1 8882742378, esi_medinfo@eisai.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001261-PIP01-11
    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
    28 Mar 2018
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Jan 2016
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To estimate maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), to define and describe toxicities, and to characterize pharmacokinetics (PK) of eribulin mesylate administered as an intravenous infusion on Day 1 and Day 8 of a 21-day cycle to children with refractory or recurrent solid tumors (excluding central nervous system [CNS]), including lymphomas.
    Protection of trial subjects
    This study was conducted in accordance with standard operating procedures (SOPs) of the sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as required by the following: - Principles of the World Medical Association Declaration of Helsinki (World Medical Association, 2008) - International Council on Harmonisation (ICH) E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - Title 21 of the United States (US) Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and Institutional Review Board (IRB) regulations and applicable sections of US 21 CFR Part 312 - European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country. All suspected unexpected serious adverse reactions were reported, as required, to the Competent Authorities of all involved EU member states. - Article 14, Paragraph 3, and Article 80-2 of the Pharmaceutical Affairs Law (Law No. 145, 1960) for studies conducted in Japan, in addition to Japan’s GCP Subject Information and Informed Consent.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Jul 2014
    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
    United States: 23
    Worldwide total number of subjects
    23
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    7
    Adolescents (12-17 years)
    16
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subjects took part in the study at 18 investigative sites in the United States from 31 July 2014 to 28 January 2016.

    Pre-assignment
    Screening details
    		 In Part A1, a total of 23 subjects of greater than or equal to (>=) 12 months were enrolled, of which 22 were treated in the study. In Part A2, the study was open for the enrolment of infant subjects of less than 12 months of age, however no subjects were enrolled into this part.

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

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2
    Arm description
    		 Subjects received eribulin mesylate (E7389) 1.1 milligram per square meter (mg/m^2), intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 4 cycles, or until progressive disease (PD) or unacceptable toxicity or drug related dose-limiting toxicities (DLT's).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eribulin Mesylate 1.1 mg/m^2
    Investigational medicinal product code
    Other name
    E7389
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eribulin mesylate 1.1 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 4 cycles, or until PD or unacceptable toxicity or DLT's.

    Arm title
    		 Part A1: Eribulin Mesylate 1.4 mg/m^2
    Arm description
    		 Subjects received eribulin mesylate 1.4 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 8 cycles, or until PD or unacceptable toxicity or drug related DLT's.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eribulin Mesylate 1.4 mg/m^2
    Investigational medicinal product code
    Other name
    E7389
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eribulin mesylate 1.4 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 4 cycles, or until PD or unacceptable toxicity or DLT's.

    Arm title
    		 Part A1: Eribulin Mesylate 1.8 mg/m^2
    Arm description
    		 Subjects received eribulin mesylate 1.8 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 5 cycles, or until PD or unacceptable toxicity or drug related DLT's.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eribulin Mesylate 1.8 mg/m^2
    Investigational medicinal product code
    Other name
    E7389
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eribulin mesylate 1.8 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 4 cycles, or until PD or unacceptable toxicity or DLT's.

    Arm title
    		 Part A1: Eribulin Mesylate PK Expansion
    Arm description
    		 Subjects received eribulin mesylate 1.4 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 2 cycles, or until PD or unacceptable toxicity or drug related DLT's for evaluation of pharmacokinetics (PK).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eribulin Mesylate 1.4 mg/m^2
    Investigational medicinal product code
    Other name
    E7389
    Pharmaceutical forms
    Injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eribulin mesylate 1.4 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 2 cycles, or until PD or unacceptable toxicity or drug related DLT's for evaluation of PK in PK expansion group.

    Number of subjects in period 1
    		Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Started
    6
    6
    5
    5
    Completed
    0
    0
    0
    0
    Not completed
    6
    6
    5
    5
         Adverse event, serious fatal
    -
    -
    -
    1
         Consent withdrawn by subject
    1
    -
    -
    -
         Physician decision
    1
    -
    1
    -
         Evidence of progressive disease
    4
    6
    4
    4

    Baseline characteristics

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    Baseline characteristics reporting groups [1]
    Reporting group title
    Part A1: Eribulin Mesylate 1.1 mg/m^2
    Reporting group description
    		 Subjects received eribulin mesylate (E7389) 1.1 milligram per square meter (mg/m^2), intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 4 cycles, or until progressive disease (PD) or unacceptable toxicity or drug related dose-limiting toxicities (DLT's).

    Reporting group title
    Part A1: Eribulin Mesylate 1.4 mg/m^2
    Reporting group description
    		 Subjects received eribulin mesylate 1.4 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 8 cycles, or until PD or unacceptable toxicity or drug related DLT's.

    Reporting group title
    Part A1: Eribulin Mesylate 1.8 mg/m^2
    Reporting group description
    		 Subjects received eribulin mesylate 1.8 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 5 cycles, or until PD or unacceptable toxicity or drug related DLT's.

    Reporting group title
    Part A1: Eribulin Mesylate PK Expansion
    Reporting group description
    		 Subjects received eribulin mesylate 1.4 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 2 cycles, or until PD or unacceptable toxicity or drug related DLT's for evaluation of pharmacokinetics (PK).

    Notes
    [1] - The number of subjects reported to be in the baseline period is not equal to the worldwide number of subjects enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Out of 23 subjects, only 22 subjects were treated in the study. The one subject that was enrolled but not treated came off study prior to the initiation of any protocol prescribed therapy and withdrew consent.
    Reporting group values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion Total
    Number of subjects
    		 6 6 5 5
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 14 ( 3.52 ) 10.7 ( 2.25 ) 13 ( 3.24 ) 12.6 ( 5.50 ) -
    Gender categorical
    Units: Subjects
        Female
    		 1 4 3 2 10
        Male
    		 5 2 2 3 12
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 0 2 1 1 4
        Not Hispanic or Latino
    		 6 4 4 4 18
    Race
    Units: Subjects
        Black or African American
    		 1 0 1 1 3
        White
    		 5 5 4 2 16
        Unknown or Not Reported
    		 0 1 0 2 3

    End points

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    End points reporting groups
    Reporting group title
    Part A1: Eribulin Mesylate 1.1 mg/m^2
    Reporting group description
    		 Subjects received eribulin mesylate (E7389) 1.1 milligram per square meter (mg/m^2), intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 4 cycles, or until progressive disease (PD) or unacceptable toxicity or drug related dose-limiting toxicities (DLT's).

    Reporting group title
    Part A1: Eribulin Mesylate 1.4 mg/m^2
    Reporting group description
    		 Subjects received eribulin mesylate 1.4 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 8 cycles, or until PD or unacceptable toxicity or drug related DLT's.

    Reporting group title
    Part A1: Eribulin Mesylate 1.8 mg/m^2
    Reporting group description
    		 Subjects received eribulin mesylate 1.8 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 5 cycles, or until PD or unacceptable toxicity or drug related DLT's.

    Reporting group title
    Part A1: Eribulin Mesylate PK Expansion
    Reporting group description
    		 Subjects received eribulin mesylate 1.4 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 2 cycles, or until PD or unacceptable toxicity or drug related DLT's for evaluation of pharmacokinetics (PK).

    Subject analysis set title
    Part A1: All Subjects
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The dose evaluable set (DES) included all subjects who were judged as DLT evaluable as recorded in the database. In order to be DLT evaluable, all subjects had to complete Cycle 1.

    Primary: Maximum Tolerated Dose (MTD) of Eribulin Mesylate

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    End point title
    		 Maximum Tolerated Dose (MTD) of Eribulin Mesylate [1]
    End point description
    MTD: maximum dose at which <one third subjects had DLT in Cycle 1. DLT: Grade 3/4 drug-related non hematological toxicity (except Grade 3 nausea, vomiting of <3 days, Grade 3 liver enzyme elevation with alanine transaminase/aspartate transaminase and gamma glutamyl transferase that returned to Grade <=1 or baseline prior to next dose; Grade 3 fever, infection, hypophosphatemia, hypokalemia, hypocalcemia/hypomagnesemia responsive to oral supplementation). Non-hematological toxicity causing >=14 days delay between treatment cycles. Haematological DLTs included: Grade 4 neutropenia/platelets<75,000/mm^3 on Day 8 that does not resolve to absolute neutrophil count >=750/mm^3 and platelets >=75,000/mm^3 by Day 11, neutropenia for >7 days; platelet count <25,000/mm^3, or required platelet transfusion, on 2 separate days within 7-day period; Grade 3 thrombocytopenia complicated by bleeding and/or required platelet transfusion; myelosuppression causing >14 days delay between treatment cycles.
    End point type
    Primary
    End point timeframe
    First dose of study drug (Baseline) up to Cycle 1 Day 21
    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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Part A1: All Subjects
    Number of subjects analysed
    20
    Units: mg/m^2
        number (not applicable)
    1.4
    No statistical analyses for this end point

    Primary: Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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    End point title
    		 Number of Subjects With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [2]
    End point description
    TEAEs were defined as those adverse events (AEs) that occurred (or worsened, if present at Baseline) after the first dose of study drug through 30 days after the last dose of study drug. An AE was defined as any untoward medical occurrence in a subjects or clinical investigation subject administered an investigational product. An AE does not necessarily have a causal relationship with medicinal product. A SAE was defined as any AE if it resulted in death or life-threatening AE or required inpatient hospitalization or prolongation of existing hospitalization or resulted in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions or was a congenital anomaly/birth defect. The safety analysis set (SAS) included all subjects who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    First dose of study drug (Baseline up to 30 days after last dose of study drug (Cycle 8 Day 38)
    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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Number of subjects analysed
    6
    6
    5
    5
    Units: Subjects
        TEAEs
    6
    6
    5
    5
        SAEs
    2
    1
    3
    4
    No statistical analyses for this end point

    Primary: Number of Subjects With Clinically Significant Change From Baseline in Clinical Laboratory Values

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    End point title
    		 Number of Subjects With Clinically Significant Change From Baseline in Clinical Laboratory Values [3]
    End point description
    The SAS included all subjects who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)
    Notes
    [3] - 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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Number of subjects analysed
    6
    6
    5
    5
    Units: Subjects
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of Subjects With Clinically Significant Vital Sign Values

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    End point title
    		 Number of Subjects With Clinically Significant Vital Sign Values [4]
    End point description
    The SAS included all subjects who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)
    Notes
    [4] - 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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Number of subjects analysed
    6
    6
    5
    5
    Units: Subjects
    0
    0
    0
    0
    No statistical analyses for this end point

    Primary: Number of Subjects With Clinically Significant Electrocardiogram (EKG)

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    End point title
    		 Number of Subjects With Clinically Significant Electrocardiogram (EKG) [5]
    End point description
    The SAS included all subjects who received at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)
    Notes
    [5] - 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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Number of subjects analysed
    6
    6
    5
    5
    Units: Subjects
        > 30 millisecond (msec)
    1
    1
    1
    0
        >60 msec
    0
    1
    0
    0
    No statistical analyses for this end point

    Primary: T 1/2: Terminal Half-life for Eribulin Mesylate

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    End point title
    		 T 1/2: Terminal Half-life for Eribulin Mesylate [6]
    End point description
    The pharmacokinetic analysis set (PAS) included all subjects who had sufficient PK data to derive at least one PK parameter. The PAS where data at specified time points was available.
    End point type
    Primary
    End point timeframe
    Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
    Notes
    [6] - 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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Number of subjects analysed
    3
    6
    5
    4
    Units: hours
        median (full range (min-max))
    37 (29.6 to 38.9)
    38.60 (23.3 to 44.3)
    44.00 (30.6 to 56.5)
    33.25 (30.2 to 45.9)
    No statistical analyses for this end point

    Primary: Cmax: Maximum Observed Plasma Concentration for Eribulin Mesylate

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    End point title
    		 Cmax: Maximum Observed Plasma Concentration for Eribulin Mesylate [7]
    End point description
    The PAS included all subjects who had sufficient PK data to derive at least one PK parameter.
    End point type
    Primary
    End point timeframe
    Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
    Notes
    [7] - 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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Number of subjects analysed
    6
    6
    5
    5
    Units: nanogram per milliliter (ng/mL)
        arithmetic mean (standard deviation)
    353.8 ( 59.24 )
    472.3 ( 158.23 )
    382.6 ( 296.97 )
    382.8 ( 247.05 )
    No statistical analyses for this end point

    Primary: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Eribulin Mesylate

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    End point title
    		 Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Eribulin Mesylate [8]
    End point description
    The PAS included all subjects who had sufficient PK data to derive at least one PK parameter.
    End point type
    Primary
    End point timeframe
    Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
    Notes
    [8] - 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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Number of subjects analysed
    6
    6
    5
    5
    Units: hours
        median (full range (min-max))
    0.170 (0.12 to 0.32)
    0.170 (0.12 to 0.22)
    0.370 (0.08 to 0.50)
    0.300 (0.17 to 0.32)
    No statistical analyses for this end point

    Primary: AUC 0-t: Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration for Eribulin Mesylate

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    End point title
    		 AUC 0-t: Area Under the Concentration-time Curve From Zero (Pre-dose) to Time of Last Quantifiable Concentration for Eribulin Mesylate [9]
    End point description
    The PAS included all subjects who had sufficient PK data to derive at least one PK parameter.
    End point type
    Primary
    End point timeframe
    Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
    Notes
    [9] - 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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Number of subjects analysed
    6
    6
    5
    5
    Units: hour*nanogram per milliliter (h*ng/mL)
        arithmetic mean (standard deviation)
    744.0 ( 353.03 )
    758.2 ( 303.38 )
    1363.0 ( 1378.53 )
    1010.8 ( 538.94 )
    No statistical analyses for this end point

    Primary: AUC 0-inf: Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time for Eribulin Mesylate

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    End point title
    		 AUC 0-inf: Area Under the Concentration-time Curve From Zero (Pre-dose) Extrapolated to Infinite Time for Eribulin Mesylate [10]
    End point description
    The PAS included all subjects who had sufficient PK data to derive at least one PK parameter. The PAS where data at specified time points was available.
    End point type
    Primary
    End point timeframe
    Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
    Notes
    [10] - 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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Number of subjects analysed
    3
    6
    5
    4
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    654.3 ( 342.72 )
    830.5 ( 331.14 )
    1556.6 ( 1619.37 )
    907.8 ( 493.59 )
    No statistical analyses for this end point

    Primary: CL: Clearance for Eribulin Mesylate

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    End point title
    		 CL: Clearance for Eribulin Mesylate [11]
    End point description
    The PAS included all subjects who had sufficient PK data to derive at least one PK parameter. The PAS where data at specified timepoints was available.
    End point type
    Primary
    End point timeframe
    Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
    Notes
    [11] - 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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Number of subjects analysed
    3
    6
    5
    4
    Units: milliliter per hour (mL/h)
        arithmetic mean (standard deviation)
    2226.7 ( 957.10 )
    1951.7 ( 469.27 )
    2483.8 ( 1190.94 )
    2348.8 ( 1437.56 )
    No statistical analyses for this end point

    Primary: Vd: Volume of Distribution for Eribulin Mesylate

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    End point title
    		 Vd: Volume of Distribution for Eribulin Mesylate [12]
    End point description
    The PAS included all subjects who had sufficient PK data to derive at least one PK parameter. The PAS where data at pacified timepoints was available.
    End point type
    Primary
    End point timeframe
    Day 1 predose and at 10, 30 minutes, 1, 2, 4, 6, 24, 48, 72, 96 or 120 hours post-dose
    Notes
    [12] - 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: Only descriptive data was planned to be analyzed for this endpoint.
    End point values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Number of subjects analysed
    3
    6
    5
    4
    Units: milliliter
        arithmetic mean (standard deviation)
    75966.7 ( 34322.34 )
    66766.7 ( 32230.40 )
    89840.0 ( 43363.96 )
    77525.0 ( 39176.64 )
    No statistical analyses for this end point

    Secondary: Number of Subjects With Best Overall Response

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    End point title
    		 Number of Subjects With Best Overall Response
    End point description
    Best Overall Response (BOR): best response recorded from start of study treatment until disease progression (PD) or recurrence based on response evaluation criteria in solid tumors (RECIST) 1.1 for target and non-target lesions. Subjects with evaluable disease were also eligible for assessment.
    End point type
    Secondary
    End point timeframe
    First dose of study drug (Baseline) up to approximately Cycle 8 (21-days treatment cycle)
    End point values
    		 Part A1: Eribulin Mesylate 1.1 mg/m^2 Part A1: Eribulin Mesylate 1.4 mg/m^2 Part A1: Eribulin Mesylate 1.8 mg/m^2 Part A1: Eribulin Mesylate PK Expansion
    Number of subjects analysed
    6
    6
    5
    5
    Units: Subjects
        SD
    1
    1
    1
    0
        PR
    1
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    First dose of study drug (Baseline) up to 30 days after last dose of study drug (Cycle 8 Day 38)
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Part A1: Eribulin Mesylate 1.1 mg/ m^2
    Reporting group description
    		 Subjects received eribulin mesylate 1.1 milligram mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 4 cycles, or until PD or unacceptable toxicity or DLT's.

    Reporting group title
    Part A1: Eribulin Mesylate 1.4 mg/ m^2
    Reporting group description
    		 Subjects received eribulin mesylate 1.4 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 8 cycles, or until PD or unacceptable toxicity or drug related DLT's.

    Reporting group title
    Part A1: Eribulin Mesylate 1.8 mg/ m^2
    Reporting group description
    		 Subjects received eribulin mesylate 1.8 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 5 cycles, or until PD or unacceptable toxicity or drug related DLT's.

    Reporting group title
    Part A1: Eribulin Mesylate PK Expansion
    Reporting group description
    		 Subjects received eribulin mesylate 1.8 mg/m^2, intravenously over 2 to 5 minutes on Days 1 and 8 of each 21-day treatment cycle for up to 2 cycles, or until PD or unacceptable toxicity or drug related DLT's for evaluation of PK.

    Serious adverse events
    		 Part A1: Eribulin Mesylate 1.1 mg/ m^2 Part A1: Eribulin Mesylate 1.4 mg/ m^2 Part A1: Eribulin Mesylate 1.8 mg/ m^2 Part A1: Eribulin Mesylate PK Expansion
    Total subjects affected by serious adverse events
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    3 / 5 (60.00%)
    4 / 5 (80.00%)
         number of deaths (all causes)
    0
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Hypoaesthesia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Paraesthesia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gingival pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 5 (40.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Laryngeal haemorrhage
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachypnoea
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Joint swelling
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Device related infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Part A1: Eribulin Mesylate 1.1 mg/ m^2 Part A1: Eribulin Mesylate 1.4 mg/ m^2 Part A1: Eribulin Mesylate 1.8 mg/ m^2 Part A1: Eribulin Mesylate PK Expansion
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 6 (100.00%)
    6 / 6 (100.00%)
    5 / 5 (100.00%)
    5 / 5 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumour pain
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    0
    1
    1
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    1
    1
    1
    Hypotension
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    3
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    2 / 5 (40.00%)
         occurrences all number
    3
    1
    2
    2
    Malaise
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Non-cardiac chest pain
         subjects affected / exposed
    2 / 6 (33.33%)
    4 / 6 (66.67%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    4
    1
    0
    Pyrexia
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    2 / 5 (40.00%)
    2 / 5 (40.00%)
         occurrences all number
    0
    2
    2
    4
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    2 / 5 (40.00%)
         occurrences all number
    0
    2
    0
    2
    Dyspnoea
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    2
    0
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 6 (16.67%)
    3 / 6 (50.00%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    4
    1
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    1
    1
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    3
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    3 / 6 (50.00%)
    2 / 6 (33.33%)
    2 / 5 (40.00%)
    1 / 5 (20.00%)
         occurrences all number
    4
    4
    2
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    4 / 6 (66.67%)
    2 / 6 (33.33%)
    2 / 5 (40.00%)
    1 / 5 (20.00%)
         occurrences all number
    6
    3
    2
    1
    Blood albumin decreased
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    2
    1
    0
    1
    Blood bilirubin increased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    0
    1
    1
    Blood calcium decreased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    0
    1
    1
    Blood chloride decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    1
    0
    1
    Blood creatinine increased
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    2
    0
    1
    Blood glucose decreased
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Blood phosphorus decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    1
    0
    2
    Blood potassium decreased
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    1
    2
    1
    Blood sodium decreased
         subjects affected / exposed
    3 / 6 (50.00%)
    2 / 6 (33.33%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    4
    2
    0
    1
    Blood urine present
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    2
    1
    1
    Electrocardiogram QT prolonged
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    2 / 5 (40.00%)
         occurrences all number
    0
    2
    1
    2
    Haemoglobin decreased
         subjects affected / exposed
    3 / 6 (50.00%)
    3 / 6 (50.00%)
    4 / 5 (80.00%)
    0 / 5 (0.00%)
         occurrences all number
    5
    5
    6
    0
    Lymphocyte count decreased
         subjects affected / exposed
    4 / 6 (66.67%)
    3 / 6 (50.00%)
    3 / 5 (60.00%)
    4 / 5 (80.00%)
         occurrences all number
    6
    11
    7
    7
    Neutrophil count decreased
         subjects affected / exposed
    5 / 6 (83.33%)
    2 / 6 (33.33%)
    4 / 5 (80.00%)
    2 / 5 (40.00%)
         occurrences all number
    10
    6
    7
    3
    Platelet count decreased
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    4 / 5 (80.00%)
    2 / 5 (40.00%)
         occurrences all number
    1
    10
    6
    3
    Protein urine present
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Weight decreased
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    1
    2
    0
    White blood cell count decreased
         subjects affected / exposed
    5 / 6 (83.33%)
    5 / 6 (83.33%)
    5 / 5 (100.00%)
    4 / 5 (80.00%)
         occurrences all number
    10
    15
    8
    5
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    1
    0
    1
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    1
    0
    1
    Tachycardia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    0
    1
    2
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Headache
         subjects affected / exposed
    2 / 6 (33.33%)
    3 / 6 (50.00%)
    3 / 5 (60.00%)
    1 / 5 (20.00%)
         occurrences all number
    3
    4
    4
    2
    Hypoaesthesia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 5 (40.00%)
         occurrences all number
    1
    0
    0
    2
    Paraesthesia
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    4 / 6 (66.67%)
    4 / 6 (66.67%)
    2 / 5 (40.00%)
    3 / 5 (60.00%)
         occurrences all number
    6
    6
    5
    4
    Lymphopenia
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    3
    1
    1
    Neutropenia
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    3
    1
    1
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    2 / 6 (33.33%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    1
    0
    0
    Constipation
         subjects affected / exposed
    2 / 6 (33.33%)
    2 / 6 (33.33%)
    3 / 5 (60.00%)
    0 / 5 (0.00%)
         occurrences all number
    3
    5
    3
    0
    Diarrhoea
         subjects affected / exposed
    0 / 6 (0.00%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    2
    1
    1
    Dyspepsia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    0
    0
    1
    Nausea
         subjects affected / exposed
    3 / 6 (50.00%)
    3 / 6 (50.00%)
    4 / 5 (80.00%)
    1 / 5 (20.00%)
         occurrences all number
    3
    7
    5
    1
    Vomiting
         subjects affected / exposed
    3 / 6 (50.00%)
    2 / 6 (33.33%)
    2 / 5 (40.00%)
    2 / 5 (40.00%)
         occurrences all number
    4
    2
    2
    2
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    3 / 5 (60.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    3
    4
    0
    Dry skin
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    0 / 5 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Pruritus
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    2
    0
    1
    1
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    0 / 6 (0.00%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    2 / 5 (40.00%)
         occurrences all number
    0
    1
    2
    2
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    2 / 5 (40.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    0
    2
    1
    Back pain
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    2 / 5 (40.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    1
    2
    0
    Bone pain
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    0 / 5 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Musculoskeletal pain
         subjects affected / exposed
    2 / 6 (33.33%)
    2 / 6 (33.33%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    2
    3
    0
    1
    Neck pain
         subjects affected / exposed
    2 / 6 (33.33%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    2
    0
    0
    1
    Pain in extremity
         subjects affected / exposed
    3 / 6 (50.00%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    2 / 5 (40.00%)
         occurrences all number
    3
    0
    0
    3
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    3 / 6 (50.00%)
    4 / 6 (66.67%)
    2 / 5 (40.00%)
    2 / 5 (40.00%)
         occurrences all number
    4
    5
    2
    2
    Hyperglycaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    2
    1
    1
    Hypermagnesaemia
         subjects affected / exposed
    0 / 6 (0.00%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    0
    0
    2
    2
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    3 / 6 (50.00%)
    0 / 5 (0.00%)
    2 / 5 (40.00%)
         occurrences all number
    1
    4
    0
    3
    Hypocalcaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    2 / 6 (33.33%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    2
    1
    1
    Hypoglycaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    0 / 5 (0.00%)
    1 / 5 (20.00%)
         occurrences all number
    1
    0
    0
    1
    Hypokalaemia
         subjects affected / exposed
    1 / 6 (16.67%)
    1 / 6 (16.67%)
    0 / 5 (0.00%)
    2 / 5 (40.00%)
         occurrences all number
    1
    1
    0
    2
    Hyponatraemia
         subjects affected / exposed
    1 / 6 (16.67%)
    0 / 6 (0.00%)
    1 / 5 (20.00%)
    1 / 5 (20.00%)
         occurrences all number
    2
    0
    1
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Feb 2015
    Amendment 01: The protocol was amended to update the schedule for the pharmacokinetic studies and the Day 8 dose modification guidelines following discussions with the IND Sponsor, Eisai Inc.
    27 Jan 2016
    Amendment 02: The Protocol has been amended to reflect modified risk information for eribulin. The list of toxicities in the protocol and the risk profile in the ICD have been updated to confirm to CAEPR Version 2.6, March 23, 2016 and have been adapted from this CAEPR version for our company-sponsored trial and includes risk revisions as required by the drug company.

    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.
    In Part A2, the study was open for the enrollment of infant subjects of less than 12 months of age, however no subjects were enrolled into this part.
    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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