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:
    A pilot trial of PEGPH20 (pegylatedhyaluronidase) in combination with avelumab (anti-PD-L1 MSB0010718C) in chemotherapy resistant pancreatic cancer

    Summary
    EudraCT number
    		 2016-004603-31
    Trial protocol
    		 ES  
    Global end of trial date
    25 Jan 2019

    Results information
    Results version number
    		 v1(current)
    This version publication date
    31 Jan 2020
    First version publication date
    31 Jan 2020
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    PH1603
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03481920
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    PH Research
    Sponsor organisation address
    General Díaz Porlier 61, 4-3, Madrid, Spain, 28006
    Public contact
    Clinical Trial Coordinator, PH Research, morgan@phresearchoncology.com
    Scientific contact
    Clinical Trial Coordinator, PH Research, morgan@phresearchoncology.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
    30 Sep 2019
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    25 Jan 2019
    Global end of trial reached?
    Yes
    Global end of trial date
    25 Jan 2019
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    1. Determine objective response rate (ORR) per RECIST v1.1 criteria of this regimen 2. Assess the safety of this combination in patients with pancreatic ductal adenocarcinoma (PDAC) 3. Determine overall survival (OS), progression free survival (PFS), and CA19-9 tumor marker response
    Protection of trial subjects
    Enoxaparin was administered to all subjects to minimize the risk of thromboembolic events and piroxicam was administered for musculoskeletal symptoms. Prophylactic use of a proton-pump inhibitor (e.g. omeprazole daily or equivalent) was also required for all patients while receiving PEGPH20.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Jan 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Efficacy
    Long term follow-up duration
    		 9 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 8
    Worldwide total number of subjects
    8
    EEA total number of subjects
    8
    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)
    5
    From 65 to 84 years
    3
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 The date of informed consent for the first subject in the study is 12/Jan/2018 and for the last subject in the study is 16/Nov/2018. All patients were recruited in Spain.

    Pre-assignment
    Screening details
    		 - All enrolled subjects are included in the Intent To Treat Population. This population has been used as the primary population for all efficacy analyses. - All subjects who receive any study medication are included in the Safety Population.

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

    Arms
    Arm title
    		 Experimental
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    PHPG20
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for injection/infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    3 mcg/Kg IV infusion over 10-12 minutes. Cycle 1: Days 1, 4, 8, 11, 15, 18; cycle 2 or more: 1Q2W

    Investigational medicinal product name
    Avelumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for solution for infusion
    Routes of administration
    Intravenous drip use
    Dosage and administration details
    10 mg/Kg over 60 minutes 1Q2W until disease progression, unacceptable toxicity, death, or withdrawal of consent

    Number of subjects in period 1
    		Experimental
    Started
    8
    Treatment administration
    7
    Completed
    7
    Not completed
    1
         Consent withdrawn by subject
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 8 8
    Age categorical
    Units: Subjects
        Adults (18-64 years)
    		 5 5
        From 65-84 years
    		 3 3
    Age continuous
    Units: years
        median (full range (min-max))
    		 59 (43 to 79) -
    Gender categorical
    Units: Subjects
        Female
    		 4 4
        Male
    		 4 4
    Race
    Units: Subjects
        Caucasian
    		 8 8
    Histologic diagnosis
    Units: Subjects
        Ductal adenocarcinoma
    		 8 8
    TNM and Stage at diagnosis
    T
    Units: Subjects
        T1
    		 1 1
        T2
    		 2 2
        T3
    		 3 3
        T4
    		 2 2
    TNM and Stage at diagnosis
    N
    Units: Subjects
        Nx
    		 2 2
        N0
    		 3 3
        N1
    		 3 3
    TNM and Stage at diagnosis
    M
    Units: Subjects
        Mx
    		 1 1
        M0
    		 6 6
        M1
    		 1 1
    TNM and Stage at diagnosis
    Stage
    Units: Subjects
        0 stage
    		 1 1
        IA
    		 1 1
        IB
    		 1 1
        IIB
    		 2 2
        III
    		 2 2
        IV
    		 1 1
    Current TNM and Stage
    T
    Units: Subjects
        Tx
    		 1 1
        T1
    		 1 1
        T2
    		 2 2
        T3
    		 2 2
        T4
    		 1 1
        UNK
    		 1 1
    Current TNM and Stage
    N
    Units: Subjects
        Nx
    		 1 1
        N0
    		 3 3
        N1
    		 4 4
    Current TNM and Stage
    M
    Units: Subjects
        M1
    		 8 8
    Current TNM and Stage
    Stage
    Units: Subjects
        IV
    		 8 8
    ECOG-PS at baseline
    Units: Subjects
        ECOG-PS 0
    		 3 3
        ECOG-PS 1
    		 5 5
    Previous treatment: radiotherapy
    Units: Subjects
        Yes
    		 2 2
        No
    		 6 6
    Previous treatment: surgery
    Number of surgeries
    Units: Subjects
        Yes
    		 4 4
        No
    		 4 4
    Previous treatments: chemotherapy
    Number of schemes of chemotherapy
    Units: Subjects
        One
    		 1 1
        Two
    		 4 4
        Three
    		 2 2
        Five
    		 1 1
    Number of locations per subject
    Units: Subjects
        One
    		 4 4
        Two
    		 2 2
        Four
    		 1 1
        Five
    		 1 1
    Height
    Units: cm
        median (full range (min-max))
    		 163.00 (150.00 to 180.00) -
    Weight
    Units: Kg
        median (full range (min-max))
    		 56.75 (45.40 to 97.00) -
    Body surface area
    Units: m2
        median (full range (min-max))
    		 1.60 (1.40 to 2.15) -
    Sistolic blood pressure
    Units: mmHg
        median (full range (min-max))
    		 133.50 (103.00 to 140.00) -
    Diastolic blood pressure
    Units: mmHg
        median (full range (min-max))
    		 79.00 (68.00 to 93.00) -
    Heart rate
    Units: Beats per minute
        median (full range (min-max))
    		 78.50 (54.00 to 103.00) -
    Time from first diagnosis to IC
    Units: months
        median (full range (min-max))
    		 17.40 (4.41 to 26.51) -
    Relative dose intensity PEGPH 20
    Units: NA
        median (full range (min-max))
    		 0.89 (0.50 to 0.99) -
    Relative dose intensity Avelumab
    Units: NA
        median (full range (min-max))
    		 0.94 (0.00 to 1.00) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Experimental
    Reporting group description
    		 -

    Primary: Best Response (RECIST v1.1)

    		 Close Top of page
    End point title
    		 Best Response (RECIST v1.1) [1]
    End point description
    End point type
    Primary
    End point timeframe
    From start of treatment to end of treatment
    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: One arm non-controlled clinical trial. Only descriptive analyses performed. No comparisons.
    End point values
    		 Experimental
    Number of subjects analysed
    7
    Units: Patients
        Progression Disease
    6
        Stable Disease
    1
    No statistical analyses for this end point

    Primary: Overall Survival

    		 Close Top of page
    End point title
    		 Overall Survival [2]
    End point description
    End point type
    Primary
    End point timeframe
    From the date of first study treatment administration until the date of the death from any cause.
    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: One arm non-controlled clinical trial. Only descriptive analyses performed. No comparisons.
    End point values
    		 Experimental
    Number of subjects analysed
    7
    Units: months
    median (confidence interval 95%)
        months
    3.29 (2.78 to 3.80)
    No statistical analyses for this end point

    Primary: Progression Free Survival

    		 Close Top of page
    End point title
    		 Progression Free Survival [3]
    End point description
    End point type
    Primary
    End point timeframe
    From the date of first study treatment administration until the date of the RECIST v1.1 progression or death from any cause, whichever occurs first.
    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: One arm non-controlled clinical trial. Only descriptive analyses performed. No comparisons.
    End point values
    		 Experimental
    Number of subjects analysed
    7
    Units: months
    median (confidence interval 95%)
        months
    1.84 (1.76 to 1.93)
    No statistical analyses for this end point

    Secondary: Inmune Response Progression Free Survival

    		 Close Top of page
    End point title
    		 Inmune Response Progression Free Survival
    End point description
    End point type
    Secondary
    End point timeframe
    From the date of first study treatment administration until the date of the IR-RECIST progression or death from any cause.
    End point values
    		 Experimental
    Number of subjects analysed
    7
    Units: months
    median (confidence interval 95%)
        months
    3.09 (0.48 to 5.71)
    No statistical analyses for this end point

    Other pre-specified: Number of treatment cycles

    		 Close Top of page
    End point title
    		 Number of treatment cycles
    End point description
    End point type
    Other pre-specified
    End point timeframe
    From first dose of study treatment until end of study treatment
    End point values
    		 Experimental
    Number of subjects analysed
    7
    Units: patients
        One
    4
        Two
    1
        Three
    2
    No statistical analyses for this end point

    Post-hoc: Objective response rate

    		 Close Top of page
    End point title
    		 Objective response rate
    End point description
    End point type
    Post-hoc
    End point timeframe
    From start of treatment to end of treatment
    End point values
    		 Experimental
    Number of subjects analysed
    7
    Units: Percentage of patients
    number (confidence interval 95%)
        Objective Response (CR+PR)
    0.0 (0.0 to 0.0)
    No statistical analyses for this end point

    Post-hoc: Clinical Benefit rate

    		 Close Top of page
    End point title
    		 Clinical Benefit rate
    End point description
    End point type
    Post-hoc
    End point timeframe
    From start of treatment to end of treatment
    End point values
    		 Experimental
    Number of subjects analysed
    7
    Units: Percentage of patients
    median (confidence interval 95%)
        Clinical benefit (CR + PR + SD)
    14.3 (0.0 to 40.2)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    From first dose of study treatment until the end of long term follow-up
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Total Subjects affected by non-serious adverse events
    Reporting group description
    		 -

    Serious adverse events
    		 Total Subjects affected by non-serious adverse events
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 7 (57.14%)
         number of deaths (all causes)
    6
         number of deaths resulting from adverse events
    0
    Nervous system disorders
    Confusional state
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Pain
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Respiratory tract infection
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Total Subjects affected by non-serious adverse events
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    Investigations
    Blood thyroid stimulating hormone decreased
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Nervous system disorders
    Muscle contractions involuntary
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    4 / 7 (57.14%)
         occurrences all number
    4
    Feeling cold
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Oedema peripheral
         subjects affected / exposed
    3 / 7 (42.86%)
         occurrences all number
    3
    Peripheral swelling
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Eye disorders
    Eye pain
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Abdominal pain upper
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Anal incontinence
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Constipation
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Diarrhoea
         subjects affected / exposed
    2 / 7 (28.57%)
         occurrences all number
    2
    Gastrooesophageal reflux disease
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Mesenteric vein thrombosis
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Nausea
         subjects affected / exposed
    2 / 7 (28.57%)
         occurrences all number
    2
    Vomiting
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Dysphonia
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Muscle spasms
         subjects affected / exposed
    5 / 7 (71.43%)
         occurrences all number
    5
    Musculoskeletal stiffness
         subjects affected / exposed
    2 / 7 (28.57%)
         occurrences all number
    2
    Myalgia
         subjects affected / exposed
    2 / 7 (28.57%)
         occurrences all number
    2
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1
    Urinary tract infection
         subjects affected / exposed
    1 / 7 (14.29%)
         occurrences all number
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Apr 2018
    A serum chemistry has been added at cycle 1, days 4, 11 and 18. New hepatic function test in Cycle 1 all visits and Cycle 2, first visit. Eligibility criteria. Study design has been modified to include a 3+3 scheme.
    27 Dec 2018
    Avelumab Investigator Brochure has been updated from 7th to 8th version and data protection regulations were updated to current regulation.

    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.
    Low number of patients included in the study.
    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 09:21:22 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA