Flag of the European Union EU Clinical Trials Register Help

Clinical trials

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

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

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Phase II, randomized, controlled, clinical trial exploring efficacy and safety of ERY001 (L-asparaginase encapsulated in Red Blood Cells) in combination with gemcitabine or FOLFOX regimen in second-line therapy for patients with progressive metastatic pancreatic carcinoma.

    Summary
    EudraCT number
    		 2013-004262-34
    Trial protocol
    		 FR  
    Global end of trial date
    07 Nov 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Feb 2022
    First version publication date
    09 Feb 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    GRASPANC 2013-03
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02195180
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Erytech Pharma
    Sponsor organisation address
    60 Avenue Rockefeller, Lyon, France, 69008
    Public contact
    Anu Gupta, ERYTECH Pharma, +1650 5634176, anu.gupta@erytech.com
    Scientific contact
    Iman El-Hariry, ERYTECH Pharma, +1617 9592131, iman.elhariry@erytech.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
    02 Dec 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Nov 2017
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The two co- primary objectives of the study were: • To evaluate of the effects of eryaspase in terms of progression-free survival (PFS) when eryaspase is combined with chemotherapy for the second-line treatment of patients with pancreatic adenocarcinoma (PAC) whose tumors have low or no asparagine synthetase (ASNS) expression (ASNS 0/1+). • To evaluate of the effects of eryaspase in terms of overall survival (OS) when eryaspase is combined with chemotherapy for the second-line treatment of patients with PAC whose tumors have low or no ASNS expression (ASNS 0/1+).
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial. An independent DSMB reviewed the interim results from the study as well as safety on a regular basis.
    Background therapy
    		 Based on systematic reviews and NCCN guidelines, gemcitabine-based therapy can be given to those previously treated with fluoropyrimidine-based chemotherapy (Tempero 2017). Fluoropyrimidine-based chemotherapy regimens are acceptable second-line options for patients who have received prior gemcitabine-based therapy. Therefore, the choice of chemotherapy as the backbone of treatment in both treatment arms was justified.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Mar 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    France: 141
    Worldwide total number of subjects
    141
    EEA total number of subjects
    141
    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)
    81
    From 65 to 84 years
    60
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 A total of 141 adult patients were randomized 2:1 ratio to two arms: Eryaspase + Chemotherapy and Chemotherapy alone, and of those, 137 patients received treatment.

    Pre-assignment
    Screening details
    		 • Advanced or metastatic exocrine pancreatic adenocarcinoma. • Only one 1 prior systemic therapy for advanced or metastatic disease. Progressed through first line. • Age 18 years or older. • Measurable lesion (>1 cm) as assessed by CT scan or MRI (RECIST criteria Version 1.1). • ECOG PS of 0 or 1.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Eryaspase + chemotherapy
    Arm description
    		 This arm received eryaspase at 100 U/kg combined with either gemcitabine or modified FOLFOX 6 regimen (mFOLFOX6, as plan protocol amendment-1 (26th Feb 2016) in second-line therapy of patients with progressive metastatic pancreatic adenocarcinoma. Choice of chemotherapy in second-line treatment was determined, depending on the chemotherapy used in the first-line. If the first-line regimen was FOLFIRINOX or a FOLFOX regime, the gemcitabine-based regimen was used. If the first-line was a gemcitabine-based regimen, FOLFIRINOX or a FOLFOX regime was used. Chemotherapy part was planned for a total of 6 cycles. However, the number of cycles was dependent on the patient's response/tolerance.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Eryaspase
    Investigational medicinal product code
    Other name
    ERY001, GRASPA
    Pharmaceutical forms
    Dispersion for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Eryaspase was administered every 2 weeks at a dose of 100 U/kg for each administration. Two administrations of eryaspase alone were planned per course of chemotherapy. Each administration was done on the third day (D3) of the first week and the third day (D17) of the third week of each chemotherapy course. Eryaspase administrations continued as long as there was no specific limiting toxicity related to investigational product.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Gemcitabine regimen consisted of 1000 mg/m², 30 min i.v perfusion at D1 weekly for 3 out of 4 weeks. A period of 4 weeks constituted a full course/cycle of chemotherapy.

    Investigational medicinal product name
    mFOLFOX6
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use, Intravenous bolus use
    Dosage and administration details
    mFOLFOX6 was administered as followed (Allegra 2011): intravenous (i.v.) oxaliplatin 85 mg/m2 on D1 or D15, i.v. leucovorin at a dose of 400 mg/m² or levo-leucovorin at a dose of 200 mg/m2 on D1 or D15, and i.v. bolus 5-FU at a dose of 400 mg/m2 and continuous intravenous infusion (c.v.i.) 5-FU at a dose of 2400 mg/m2 on D1 and D2 or D15 and D16. The treatment was repeated every 2 weeks. Two consecutive period of 2 weeks (total of 4 weeks) constituted a full course/cycle of chemotherapy.

    Arm title
    		 Chemotherapy alone
    Arm description
    		 Chemotherapy alone (without study treatment eryaspase) was planned for a total of 6 cycles. However, the number of cycles was dependent on the patient's response/tolerance. Patients received successive courses of chemotherapy according to investigator decision (gemcitabine or mFOLFOX6). The modified FOLFOX 6 regimen (mFOLFOX6, as plan protocol amendment-1 (26th Feb 2016) in second-line therapy of patients with progressive metastatic pancreatic adenocarcinoma. Choice of chemotherapy in second-line treatment was determined, depending on the chemotherapy used in the first-line. If the first-line regimen was FOLFIRINOX or a FOLFOX regime, the gemcitabine-based regimen was used. If the first-line was a gemcitabine-based regimen, FOLFIRINOX or a FOLFOX regime was used. Chemotherapy part was planned for a total of 6 cycles. However, the number of cycles was dependent on the patient's response/tolerance.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Gemcitabine regimen consisted in 1000 mg/m², 30 min i.v perfusion at D1 weekly for 3 out of 4 weeks. A period of 4 weeks constituted a full course/cycle of chemotherapy.

    Investigational medicinal product name
    mFOLFOX6
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    mFOLFOX6 was administered as followed (Allegra 2011): intravenous (i.v.) oxaliplatin 85 mg/m2 on D1 or D15, i.v. leucovorin at a dose of 400 mg/m² or levo-leucovorin at a dose of 200 mg/m2, and i.v. bolus 5-FU at a dose of 400 mg/m2 and continuous intravenous infusion (c.v.i.) 5-FU at a dose of 2400 mg/m2 on D1 and D2 or D15 and D16. The treatment was repeated every 2 weeks. Two consecutive period of 2 weeks (total of 4 weeks) constituted a full course/cycle of chemotherapy.

    Number of subjects in period 1
    		Eryaspase + chemotherapy Chemotherapy alone
    Started
    95
    46
    Completed
    90
    43
    Not completed
    5
    3
         Consent withdrawn by subject
    3
    2
         health deterioration
    2
    -
         Protocol deviation
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Eryaspase + chemotherapy
    Reporting group description
    		 This arm received eryaspase at 100 U/kg combined with either gemcitabine or modified FOLFOX 6 regimen (mFOLFOX6, as plan protocol amendment-1 (26th Feb 2016) in second-line therapy of patients with progressive metastatic pancreatic adenocarcinoma. Choice of chemotherapy in second-line treatment was determined, depending on the chemotherapy used in the first-line. If the first-line regimen was FOLFIRINOX or a FOLFOX regime, the gemcitabine-based regimen was used. If the first-line was a gemcitabine-based regimen, FOLFIRINOX or a FOLFOX regime was used. Chemotherapy part was planned for a total of 6 cycles. However, the number of cycles was dependent on the patient's response/tolerance.

    Reporting group title
    Chemotherapy alone
    Reporting group description
    		 Chemotherapy alone (without study treatment eryaspase) was planned for a total of 6 cycles. However, the number of cycles was dependent on the patient's response/tolerance. Patients received successive courses of chemotherapy according to investigator decision (gemcitabine or mFOLFOX6). The modified FOLFOX 6 regimen (mFOLFOX6, as plan protocol amendment-1 (26th Feb 2016) in second-line therapy of patients with progressive metastatic pancreatic adenocarcinoma. Choice of chemotherapy in second-line treatment was determined, depending on the chemotherapy used in the first-line. If the first-line regimen was FOLFIRINOX or a FOLFOX regime, the gemcitabine-based regimen was used. If the first-line was a gemcitabine-based regimen, FOLFIRINOX or a FOLFOX regime was used. Chemotherapy part was planned for a total of 6 cycles. However, the number of cycles was dependent on the patient's response/tolerance.

    Reporting group values
    		 Eryaspase + chemotherapy Chemotherapy alone Total
    Number of subjects
    		 95 46 141
    Age categorical
    Adults (18 years or older)
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 0 0 0
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
        <65 years
    		 52 29 81
        >65 years
    		 43 17 60
    Gender categorical
    Units: Subjects
        Female
    		 42 16 58
        Male
    		 53 30 83
    ECOG Status
    Eastern Cooperative Oncology Group (ECOG) performance status (PS) was evaluated (0 or 1)
    Units: Subjects
        ECOG PS 0
    		 30 12 42
        ECOG PS 1
    		 65 34 99
    Subject analysis sets

    Subject analysis set title
    Intend-to-treat (ITT)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT population comprised all patients who were randomized to study treatment, regardless of whether they received study medication.

    Subject analysis set title
    Per Protocol (PP)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The PP population included all patients in the ITT population who received at least 1 dose of study medication and who met all of the following criteria: • Had no major deviation in inclusion/exclusion criteria. • Had at least 1radiological assessment post-baseline.

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety population is defined as all patients who received at least one dose of study drug.

    Subject analysis set title
    ITT, ASNS 0/1
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subset of the ITT analysis set with ASNS 0/1 expressing tumours

    Subject analysis set title
    PP, ASNS 0/1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subset of PP analysis set with ASNS 0/1 expressing tumours

    Subject analysis set title
    ITT ASNS 2+/3+
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT population of patients with ASNS status 2+ ot 3+ is defined as all patients randomized.

    Subject analysis set title
    PP ASNS 2+/3+
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The per protocol population of patients with ASNS status of 2+ or 3+. It is defined as all patients in the ITT set who receive at least one dose of study medication and who meet all of the following criteria: Satisfy the Inclusion/exclusion criteria; Correct treatment group allocation according to randomization; No additional prohibited chemotherapy during the treatment phase; No prohibited concomitant medications. Major protocol violations leading to treatment or study discontinuation would exclude patients from the per protocol population.

    Subject analysis sets values
    		 Intend-to-treat (ITT) Per Protocol (PP) Safety population ITT, ASNS 0/1 PP, ASNS 0/1 ITT ASNS 2+/3+ PP ASNS 2+/3+
    Number of subjects
    141
    135
    137
    98
    95
    43
    40
    Age categorical
    Adults (18 years or older)
    Units: Subjects
        In utero
    0
    0
    0
    0
    0
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
    0
    0
    0
    0
    0
        Newborns (0-27 days)
    0
    0
    0
    0
    0
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
    0
    0
    0
    0
    0
        Children (2-11 years)
    0
    0
    0
    0
    0
    0
    0
        Adolescents (12-17 years)
    0
    0
    0
    0
    0
    0
    0
        Adults (18-64 years)
    0
    0
    0
    0
    0
    0
    0
        From 65-84 years
    0
    0
    0
    0
    0
    0
    0
        85 years and over
    0
    0
    0
    0
    0
    0
    0
        <65 years
    81
    77
    78
    53
    51
    28
    26
        >65 years
    60
    58
    59
    45
    44
    15
    14
    Age continuous
    Units:
        
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    58
    56
    57
    43
    42
    15
    14
        Male
    83
    79
    80
    55
    53
    28
    26
    ECOG Status
    Eastern Cooperative Oncology Group (ECOG) performance status (PS) was evaluated (0 or 1)
    Units: Subjects
        ECOG PS 0
    42
    40
    40
    27
    26
    15
    14
        ECOG PS 1
    99
    95
    97
    71
    69
    27
    26

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Eryaspase + chemotherapy
    Reporting group description
    		 This arm received eryaspase at 100 U/kg combined with either gemcitabine or modified FOLFOX 6 regimen (mFOLFOX6, as plan protocol amendment-1 (26th Feb 2016) in second-line therapy of patients with progressive metastatic pancreatic adenocarcinoma. Choice of chemotherapy in second-line treatment was determined, depending on the chemotherapy used in the first-line. If the first-line regimen was FOLFIRINOX or a FOLFOX regime, the gemcitabine-based regimen was used. If the first-line was a gemcitabine-based regimen, FOLFIRINOX or a FOLFOX regime was used. Chemotherapy part was planned for a total of 6 cycles. However, the number of cycles was dependent on the patient's response/tolerance.

    Reporting group title
    Chemotherapy alone
    Reporting group description
    		 Chemotherapy alone (without study treatment eryaspase) was planned for a total of 6 cycles. However, the number of cycles was dependent on the patient's response/tolerance. Patients received successive courses of chemotherapy according to investigator decision (gemcitabine or mFOLFOX6). The modified FOLFOX 6 regimen (mFOLFOX6, as plan protocol amendment-1 (26th Feb 2016) in second-line therapy of patients with progressive metastatic pancreatic adenocarcinoma. Choice of chemotherapy in second-line treatment was determined, depending on the chemotherapy used in the first-line. If the first-line regimen was FOLFIRINOX or a FOLFOX regime, the gemcitabine-based regimen was used. If the first-line was a gemcitabine-based regimen, FOLFIRINOX or a FOLFOX regime was used. Chemotherapy part was planned for a total of 6 cycles. However, the number of cycles was dependent on the patient's response/tolerance.

    Subject analysis set title
    Intend-to-treat (ITT)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT population comprised all patients who were randomized to study treatment, regardless of whether they received study medication.

    Subject analysis set title
    Per Protocol (PP)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The PP population included all patients in the ITT population who received at least 1 dose of study medication and who met all of the following criteria: • Had no major deviation in inclusion/exclusion criteria. • Had at least 1radiological assessment post-baseline.

    Subject analysis set title
    Safety population
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The safety population is defined as all patients who received at least one dose of study drug.

    Subject analysis set title
    ITT, ASNS 0/1
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Subset of the ITT analysis set with ASNS 0/1 expressing tumours

    Subject analysis set title
    PP, ASNS 0/1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subset of PP analysis set with ASNS 0/1 expressing tumours

    Subject analysis set title
    ITT ASNS 2+/3+
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The ITT population of patients with ASNS status 2+ ot 3+ is defined as all patients randomized.

    Subject analysis set title
    PP ASNS 2+/3+
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The per protocol population of patients with ASNS status of 2+ or 3+. It is defined as all patients in the ITT set who receive at least one dose of study medication and who meet all of the following criteria: Satisfy the Inclusion/exclusion criteria; Correct treatment group allocation according to randomization; No additional prohibited chemotherapy during the treatment phase; No prohibited concomitant medications. Major protocol violations leading to treatment or study discontinuation would exclude patients from the per protocol population.

    Primary: Progression-free survival (PFS), ASNS 0/1

    		 Close Top of page
    End point title
    		 Progression-free survival (PFS), ASNS 0/1
    End point description
    PFS defined as the time elapsed between randomisation and death from any cause or progression. For any patients who had not progressed or died at the time of database lock, PFS was censored at the date of last radiological assessment prior to database lock.
    End point type
    Primary
    End point timeframe
    Complete study period
    End point values
    		 Eryaspase + chemotherapy Chemotherapy alone
    Number of subjects analysed
    56
    29
    Units: months
        median (confidence interval 95%)
    2.1 (1.7 to 3.4)
    2.5 (1.4 to 3.4)
    Statistical analysis title
    		 PFS, ASNS 0/1
    Statistical analysis description
    Stratified log-rank test, with the stratification variable being the type of chemotherapy treatment (gemcitabine or mFOLFOX6).
    Comparison groups
    Eryaspase + chemotherapy v Chemotherapy alone
    Number of subjects included in analysis
    85
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.124 [1]
    Method
    		 Stratified logrank test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.4
         upper limit
    		 1.12
    Notes
    [1] - Not statistically significant different for PFS in the ASNS 0/1 subgroup

    Primary: Overall survival (OS), ASNS 0/1

    		 Close Top of page
    End point title
    		 Overall survival (OS), ASNS 0/1
    End point description
    OS defined as the time elapsed between randomisation and death from any cause. For any patients who had not died at the time of database lock, OS was censored at the date of last contact before database lock.
    End point type
    Primary
    End point timeframe
    Complete study period
    End point values
    		 Eryaspase + chemotherapy Chemotherapy alone
    Number of subjects analysed
    66
    32
    Units: months
        median (confidence interval 95%)
    6.2 (5.1 to 8.8)
    4.9 (3.1 to 7.1)
    Statistical analysis title
    		 OS, ASNS 0/1
    Statistical analysis description
    Stratified log-rank test, with the stratification variable being the type of chemotherapy treatment (gemcitabine or mFOLFOX6).
    Comparison groups
    Eryaspase + chemotherapy v Chemotherapy alone
    Number of subjects included in analysis
    98
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.054 [2]
    Method
    		 Stratified logrank test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.39
         upper limit
    		 1.01
    Notes
    [2] - Approaching statistical significance at the 5% level. Weak evidence supporting differences for OS in the ASNS 0/1 subgroup

    Secondary: Progression-free survival (PFS)

    		 Close Top of page
    End point title
    		 Progression-free survival (PFS)
    End point description
    PFS in ITT analysis set
    End point type
    Secondary
    End point timeframe
    Complete study period
    End point values
    		 Eryaspase + chemotherapy Chemotherapy alone
    Number of subjects analysed
    95
    46
    Units: months
        median (confidence interval 95%)
    2.1 (1.8 to 3.4)
    1.6 (1.3 to 3.0)
    Statistical analysis title
    		 PFS, ITT
    Comparison groups
    Eryaspase + chemotherapy v Chemotherapy alone
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.005 [3]
    Method
    		 Stratified logrank test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.37
         upper limit
    		 0.84
    Notes
    [3] - Statistically significant differences for PFS in the ITT analysis set

    Secondary: Overall survival (OS)

    		 Close Top of page
    End point title
    		 Overall survival (OS)
    End point description
    OS in ITT analysis set
    End point type
    Secondary
    End point timeframe
    Complete study period
    End point values
    		 Eryaspase + chemotherapy Chemotherapy alone
    Number of subjects analysed
    95
    46
    Units: months
        median (confidence interval 95%)
    6.0 (4.8 to 6.6)
    4.4 (3.0 to 5.0)
    Statistical analysis title
    		 OS, ITT
    Comparison groups
    Eryaspase + chemotherapy v Chemotherapy alone
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.007 [4]
    Method
    		 Stratified logrank test
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.41
         upper limit
    		 0.87
    Notes
    [4] - Statistically significant differences for OS in ITT analysis set

    Secondary: Objective response

    		 Close Top of page
    End point title
    		 Objective response
    End point description
    Objective response was defined as tumour response (complete response [CR] or partial response [PR]) per modified RECIST V1.1.
    End point type
    Secondary
    End point timeframe
    Complete study period
    End point values
    		 Eryaspase + chemotherapy Chemotherapy alone Intend-to-treat (ITT)
    Number of subjects analysed
    95
    46
    141
    Units: binary
    9
    4
    13
    No statistical analyses for this end point

    Secondary: Disease control

    		 Close Top of page
    End point title
    		 Disease control
    End point description
    Disease control was defined as CR, PR, or stable disease for at least 16 weeks, as determined by modified RECIST V1.1.
    End point type
    Secondary
    End point timeframe
    Complete study period
    End point values
    		 Eryaspase + chemotherapy Chemotherapy alone Intend-to-treat (ITT)
    Number of subjects analysed
    95
    46
    141
    Units: binary
    46
    11
    57
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From the first trial-related activity after the patient had signed the ICF until 4 weeks after the last administration of study drug.
    Adverse event reporting additional description
    All adverse events (AE) were followed until resolution or until 4 weeks after the last administration of study treatment. Serious adverse events (SAEs) were recorded throughout the study duration and followed until the subject has recovered, stabilized, recovered with sequelae or died. Adverse events were assessed at each visit and recorded in eCRF
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    17.1
    Reporting groups
    Reporting group title
    Eryaspase + Chemotherapy
    Reporting group description
    		 Safety population

    Reporting group title
    Chemotherapy alone
    Reporting group description
    		 Safety population

    Serious adverse events
    		 Eryaspase + Chemotherapy Chemotherapy alone
    Total subjects affected by serious adverse events
         subjects affected / exposed
    42 / 93 (45.16%)
    22 / 44 (50.00%)
         number of deaths (all causes)
    10
    8
         number of deaths resulting from adverse events
    10
    8
    Vascular disorders
    Jugular vein thrombosis
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Phlebitis
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Venous thrombosis
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    General physical health deterioration
         subjects affected / exposed
    7 / 93 (7.53%)
    4 / 44 (9.09%)
         occurrences causally related to treatment / all
    0 / 7
    0 / 4
         deaths causally related to treatment / all
    0 / 4
    0 / 4
    Asthenia
         subjects affected / exposed
    1 / 93 (1.08%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    4 / 93 (4.30%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disease progression
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Generalised oedema
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malaise
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperthermia
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 93 (1.08%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 1
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    2 / 93 (2.15%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional state
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Product issues
    Device occlusion
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombosis in device
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    Antibody test positive
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Transfusion reaction
         subjects affected / exposed
    3 / 93 (3.23%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    3 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebrovascular disorder
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    coma
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    1 / 93 (1.08%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 93 (1.08%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    4 / 93 (4.30%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 93 (2.15%)
    3 / 44 (6.82%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subileus
         subjects affected / exposed
    4 / 93 (4.30%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    1 / 93 (1.08%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 93 (2.15%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Duodenal stenosis
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mesenteric vein thrombosis
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Jaundice
         subjects affected / exposed
    3 / 93 (3.23%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Bile duct stenosis
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis
         subjects affected / exposed
    2 / 93 (2.15%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholangitis acute
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Jaundice cholestatic
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Renal colic
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Sepsis
         subjects affected / exposed
    1 / 93 (1.08%)
    2 / 44 (4.55%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    2 / 93 (2.15%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 2
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia klebsiella
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis septic
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    1 / 93 (1.08%)
    1 / 44 (2.27%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Decreased appetite
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypoglycaemia
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 44 (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
    		 Eryaspase + Chemotherapy Chemotherapy alone
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    93 / 93 (100.00%)
    44 / 44 (100.00%)
    Investigations
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    18 / 93 (19.35%)
    11 / 44 (25.00%)
         occurrences all number
    27
    14
    Weight decreased
         subjects affected / exposed
    15 / 93 (16.13%)
    9 / 44 (20.45%)
         occurrences all number
    18
    11
    Alloimmunisation
         subjects affected / exposed
    15 / 93 (16.13%)
    0 / 44 (0.00%)
         occurrences all number
    15
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    8 / 93 (8.60%)
    4 / 44 (9.09%)
         occurrences all number
    11
    5
    Blood bilirubin increased
         subjects affected / exposed
    8 / 93 (8.60%)
    1 / 44 (2.27%)
         occurrences all number
    12
    1
    Antithrombin III decreased
         subjects affected / exposed
    7 / 93 (7.53%)
    0 / 44 (0.00%)
         occurrences all number
    11
    0
    Neutrophil count decreased
         subjects affected / exposed
    6 / 93 (6.45%)
    1 / 44 (2.27%)
         occurrences all number
    7
    1
    Platelet count decreased
         subjects affected / exposed
    5 / 93 (5.38%)
    2 / 44 (4.55%)
         occurrences all number
    9
    3
    Alanine aminotransferase increased
         subjects affected / exposed
    14 / 93 (15.05%)
    2 / 44 (4.55%)
         occurrences all number
    24
    2
    Nervous system disorders
    Dysgeusia
         subjects affected / exposed
    8 / 93 (8.60%)
    4 / 44 (9.09%)
         occurrences all number
    10
    4
    Headache
         subjects affected / exposed
    9 / 93 (9.68%)
    1 / 44 (2.27%)
         occurrences all number
    14
    1
    Paraesthesia
         subjects affected / exposed
    6 / 93 (6.45%)
    4 / 44 (9.09%)
         occurrences all number
    7
    4
    Neuropathy peripheral
         subjects affected / exposed
    13 / 93 (13.98%)
    9 / 44 (20.45%)
         occurrences all number
    28
    14
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    63 / 93 (67.74%)
    28 / 44 (63.64%)
         occurrences all number
    132
    55
    Pyrexia
         subjects affected / exposed
    27 / 93 (29.03%)
    12 / 44 (27.27%)
         occurrences all number
    51
    21
    General physical health deterioration
         subjects affected / exposed
    13 / 93 (13.98%)
    3 / 44 (6.82%)
         occurrences all number
    14
    3
    Oedema peripheral
         subjects affected / exposed
    16 / 93 (17.20%)
    7 / 44 (15.91%)
         occurrences all number
    19
    7
    Fatigue
         subjects affected / exposed
    11 / 93 (11.83%)
    7 / 44 (15.91%)
         occurrences all number
    40
    26
    Mucosal inflammation
         subjects affected / exposed
    11 / 93 (11.83%)
    3 / 44 (6.82%)
         occurrences all number
    11
    5
    Chills
         subjects affected / exposed
    8 / 93 (8.60%)
    0 / 44 (0.00%)
         occurrences all number
    12
    0
    Oedema
         subjects affected / exposed
    1 / 93 (1.08%)
    1 / 44 (2.27%)
         occurrences all number
    1
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    42 / 93 (45.16%)
    23 / 44 (52.27%)
         occurrences all number
    100
    52
    Thrombocytopenia
         subjects affected / exposed
    40 / 93 (43.01%)
    16 / 44 (36.36%)
         occurrences all number
    104
    40
    Neutropenia
         subjects affected / exposed
    23 / 93 (24.73%)
    7 / 44 (15.91%)
         occurrences all number
    39
    16
    Lymphopenia
         subjects affected / exposed
    10 / 93 (10.75%)
    3 / 44 (6.82%)
         occurrences all number
    17
    6
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    58 / 93 (62.37%)
    26 / 44 (59.09%)
         occurrences all number
    102
    31
    Vomiting
         subjects affected / exposed
    42 / 93 (45.16%)
    15 / 44 (34.09%)
         occurrences all number
    73
    23
    Abdominal pain
         subjects affected / exposed
    34 / 93 (36.56%)
    16 / 44 (36.36%)
         occurrences all number
    45
    27
    Diarrhoea
         subjects affected / exposed
    37 / 93 (39.78%)
    13 / 44 (29.55%)
         occurrences all number
    66
    15
    Constipation
         subjects affected / exposed
    26 / 93 (27.96%)
    12 / 44 (27.27%)
         occurrences all number
    30
    17
    Abdominal pain upper
         subjects affected / exposed
    14 / 93 (15.05%)
    9 / 44 (20.45%)
         occurrences all number
    18
    11
    Stomatitis
         subjects affected / exposed
    15 / 93 (16.13%)
    5 / 44 (11.36%)
         occurrences all number
    25
    5
    Haemorrhoids
         subjects affected / exposed
    8 / 93 (8.60%)
    3 / 44 (6.82%)
         occurrences all number
    8
    3
    Ascites
         subjects affected / exposed
    6 / 93 (6.45%)
    4 / 44 (9.09%)
         occurrences all number
    44
    4
    Gastrooesophageal reflux disease
         subjects affected / exposed
    7 / 93 (7.53%)
    2 / 44 (4.55%)
         occurrences all number
    7
    3
    Dry mouth
         subjects affected / exposed
    3 / 93 (3.23%)
    3 / 44 (6.82%)
         occurrences all number
    3
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    11 / 93 (11.83%)
    3 / 44 (6.82%)
         occurrences all number
    15
    4
    Dyspnoea
         subjects affected / exposed
    9 / 93 (9.68%)
    4 / 44 (9.09%)
         occurrences all number
    9
    4
    Epistaxis
         subjects affected / exposed
    8 / 93 (8.60%)
    1 / 44 (2.27%)
         occurrences all number
    10
    1
    Pulmonary embolism
         subjects affected / exposed
    4 / 93 (4.30%)
    1 / 44 (2.27%)
         occurrences all number
    4
    1
    Productive cough
         subjects affected / exposed
    2 / 93 (2.15%)
    3 / 44 (6.82%)
         occurrences all number
    2
    3
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    2 / 93 (2.15%)
    1 / 44 (2.27%)
         occurrences all number
    3
    1
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    11 / 93 (11.83%)
    1 / 44 (2.27%)
         occurrences all number
    23
    3
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    10 / 93 (10.75%)
    6 / 44 (13.64%)
         occurrences all number
    11
    6
    Insomnia
         subjects affected / exposed
    8 / 93 (8.60%)
    6 / 44 (13.64%)
         occurrences all number
    8
    7
    Sleep disorder
         subjects affected / exposed
    1 / 93 (1.08%)
    2 / 44 (4.55%)
         occurrences all number
    1
    2
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    12 / 93 (12.90%)
    5 / 44 (11.36%)
         occurrences all number
    15
    7
    Myalgia
         subjects affected / exposed
    7 / 93 (7.53%)
    3 / 44 (6.82%)
         occurrences all number
    8
    3
    Arthralgia
         subjects affected / exposed
    5 / 93 (5.38%)
    2 / 44 (4.55%)
         occurrences all number
    9
    4
    Pain in extremity
         subjects affected / exposed
    5 / 93 (5.38%)
    3 / 44 (6.82%)
         occurrences all number
    6
    3
    Musculoskeletal pain
         subjects affected / exposed
    6 / 93 (6.45%)
    0 / 44 (0.00%)
         occurrences all number
    7
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    3 / 93 (3.23%)
    2 / 44 (4.55%)
         occurrences all number
    3
    2
    Urinary tract infection
         subjects affected / exposed
    5 / 93 (5.38%)
    0 / 44 (0.00%)
         occurrences all number
    6
    0
    Sepsis
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 44 (2.27%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    29 / 93 (31.18%)
    16 / 44 (36.36%)
         occurrences all number
    31
    20
    Hypoalbuminaemia
         subjects affected / exposed
    8 / 93 (8.60%)
    8 / 44 (18.18%)
         occurrences all number
    13
    8
    Hypokalaemia
         subjects affected / exposed
    13 / 93 (13.98%)
    3 / 44 (6.82%)
         occurrences all number
    24
    4
    Hyperglycaemia
         subjects affected / exposed
    11 / 93 (11.83%)
    2 / 44 (4.55%)
         occurrences all number
    23
    2
    Hyponatraemia
         subjects affected / exposed
    6 / 93 (6.45%)
    4 / 44 (9.09%)
         occurrences all number
    6
    5
    Iron deficiency
         subjects affected / exposed
    0 / 93 (0.00%)
    3 / 44 (6.82%)
         occurrences all number
    0
    3

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Feb 2016
    Main changes in Amendment 1 include: 1. Statistical considerations 1.1. Increase in number of patients enrolled in the study from 90 to ~133 taking into account that 40% PFS rate at 16 weeks in the ERY001 arm would be considered clinically meaningful for further investigation. 1.2. Update of study objectives and endpoints to align with clinical development plan for ERY001. 1.3. Clarification on study population definition included in the study. No addition data are needed related to update items 1.2 &1.3. 1.4. Overall safety follow-up at least 1year post administration 2. Safety 2.1. Update ERY001 safety information based on most recent experience with IMP. 2.2. Implementation of recommendations from the DSMB regarding the dose adjustment rules 3. PKPD assessment: 3.1. Removal of pharmacokinetic (asparaginase activity) and pharmacodynamic (asparagine depletion) 3.2. Change of laboratory facilities from CRS to SGS Cephac for amino-acid and asparaginase activity assays for the initial samples drawn 3.3. Possibility to perform PKPD and/or DNA collection after the end of the trial for research purpose. Complementary information for ongoing patients. 4. Other clarification / complementary Information: 4.1. Clarification that the name of FOLFOX regiment utilized in the study is mFOLFOX6 vs. FOLFOX4. The predefine regimen has not been modified 4.2. Study Termination clarification 4.3. ICF updated related to the PKPD removal 4.4. Language and/or typing errors improvement,

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

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

    European Medicines Agency © 1995-Sun May 05 11:16:26 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA