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   43861   clinical trials with a EudraCT protocol, of which   7284   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

    Print Download

    Summary
    EudraCT Number:2013-004262-34
    Sponsor's Protocol Code Number:GRASPANC2013-03
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2014-02-28
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2013-004262-34
    A.3Full title of the trial
    Phase II, randomized, controlled, clinical trial exploring efficacy and safety of ERY001 (L-asparaginase encapsulated in Red Blood Cells) in association with gemcitabine or FOLFOX4 in second-line therapy for patients with progressive metastatic pancreatic carcinoma.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Clinical trial with L-asparaginase encapsulated in erythrcoytes in patients affected by metastatic pancreatic cancer after first line treatment
    A.4.1Sponsor's protocol code numberGRASPANC2013-03
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorERYTECH Pharma
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportERYTECH Pharma
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationERYTECH Pharma
    B.5.2Functional name of contact pointJerome Bailly
    B.5.3 Address:
    B.5.3.1Street AddressBâtiment Adénine - 60 Avenue Rockefeller
    B.5.3.2Town/ cityLYON
    B.5.3.3Post code69008
    B.5.3.4CountryFrance
    B.5.4Telephone number33478 78 93 04
    B.5.5Fax number3344 78 75 56 29
    B.5.6E-mailvsemareg@erytech.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/09/633
    D.3 Description of the IMP
    D.3.2Product code ERY001
    D.3.4Pharmaceutical form Suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNL-asparaginase encapsulated in erythrocytes
    D.3.9.2Current sponsor codeL-asparaginase encapsulated in erythrocytes
    D.3.10 Strength
    D.3.10.1Concentration unit IU/kg international unit(s)/kilogram
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number78 to 146
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Pancreatic cancer
    E.1.1.1Medical condition in easily understood language
    Pancreatic cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.1
    E.1.2Level LLT
    E.1.2Classification code 10051971
    E.1.2Term Pancreatic adenocarcinoma
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to determine the potential improvement of Progression Free Survival (PFS) rate at 16 weeks with ERY001 combined with gemcitabine or FOLFOX4 chemotherapy, in a population of patients with progressive metastatic pancreatic adenocarcinoma, after progression under a first line of chemotherapy, over 18 years.
    E.2.2Secondary objectives of the trial
    Secondary
    - Assess the overall tolerance of ERY001 in combination with gemcitabine or FOLFOX4 chemotherapy as second line of chemotherapy.
    - Evaluate tumor response through clinical and biological markers over time
    - Evaluate PK/PD and immunogenicity parameters of ERY001
    - Evaluate treatment adherence
    - Assess potential association between response and ASNS expression level (no or weak) on tumor
    - Evaluation of the Quality of Life

    Exploratory
    - To assess circulating tumor DNA: The aim is to assess the predictive value of circulating tumor DNA variations during the course of treatment. All patients will be eligible for circulating tumor DNA analysis.
    - To assess tumor responses by using new imaging methods and new tumor assessments criteria
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Patients with progressive metastatic exocrine pancreatic adenocarcinoma, confirmed histologically
    - Patients with available histology specimen, either from primary tumor and/or from metastatic lesions. The IHC analyses (done in a central laboratory) issued from these specimens MUST allow determining the level of asparagine synthetase expression. Such result is mandatory for the final analysis
    - Patient eligible to 2nd line gemcitabine or FOLFOX4 treatment according investigator’s decision.
    - Measurable lesion (>1cm) as assessed by CT scan or MRI (Magnetic Resonance Imaging) according to RECIST criteria (version 1.1)
    - Patient aged 18 years and older
    - ECOG (WHO) performance status 0-1
    - Signed Informed Consent
    - Patient beneficiary of a Social Security Insurance if applicable
    During the selection period, any study related examination not required for the standard diagnosis must be performed after signature of the informed consent
    E.4Principal exclusion criteria
    - Patient with cerebral metastasis
    - Patient with resectable or borderline non metastatic pancreatic adenocarcinoma
    - Patient with known hypersensitivity to L-asparaginase or have had prior exposure to any form of L-asparaginase
    - Anti-vitamin K treatment. Replacement with low molecular weight heparin treatment if required
    - Patient unable to receive treatments based on gemcitabine or FOLFOX4 or ERY001, due to general or visceral conditions unrelated to pancreatic cancer such as:
    * Bone marrow impairment as evidenced by hemoglobin < 9.0 g/dl, neutrophil count < 1.5 x 109/L, platelets < 100 x 109/L.
    * Liver or pancreatic function abnormalities
    AST or ALT > 3 x ULN, or
    Total bilirubin > 1.5 x ULN, or
    Lipase > 2N (grade 2) with suggestive clinical sign or > 3N without suggestive clinical sign
    * Renal insufficiency: Renal clearance determined by the Cockroft and Gault Formula  60 mL/min
    * Current or prior coagulopathy disorders
    PT ≥1.5 fold the upper limit of normal value or
    INR ≥1.5 fold the upper limit of normal value or
    Fibrinogen ≤ 0.75 fold the lower limit of normal value
    * Infection: HIV, active hepatitis related to B or C virus
    * Concurrent active malignancies (with the exception of in situ carcinoma of the cervix and inactive non melanoma skin cancer)
    * Other serious conditions than pancreatic cancer according to investigator's opinion
    * NYHA Grade ≥ 2 congestive heart failure
    - Systemic chemotherapy or radiation within the last 3 weeks or major surgery within 4 weeks
    - History of grade 3 blood transfusion reaction (life threatening situation)
    - Presence of rare and dangerous anti-erythrocyte antibodies preventing from getting a compatible packed Red Blood Cells for the patient
    - Patient already included in another clinical trial, 30 days prior inclusion
    - Women of child-bearing potential and men with partners of childbearing potential without effective contraception as well as pregnant or breast feeding women.
    - Patients whose regular follow-up is impossible due to psychological, family, social or geographical reasons
    E.5 End points
    E.5.1Primary end point(s)
    PFS rate of ASNS 0-1 patients with ERY001 at Month 4 (week 16).
    Progression is defined as per local evaluation as:
    - appearance of one or more new lesions,
    - increase in the size of target measurable lesions (greater than or equal to 20% of the sum of the largest diameters according to RECIST criteria version 1.1)
    Progression-free survival is defined as the time from randomization to time of objective disease progression or death related to medical condition.
    Medical images will be centrally reviewed. These central reads RECIST data will be supportive only and will be performed as sensitivity analysis.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Timepoint(s) of evaluation of Primary end points are described in E.5.1
    E.5.2Secondary end point(s)
    Secondary endpoints:
    - Overall tolerance of the Frequency, severity and relationship to study treatments drug of AE
    - Time to progression, (TTP), disease control rate, and survival rates over time up to 24 weeks, (DCR), overall survival (OS),) and event free survival (EFS) over time up to 24 weeks:
    * Time to progression is defined as the time from randomization to time of objective disease progression.
    * Disease control rate is defined as the percentage of patients who achieved disease control overtime following randomization. Disease control at 24 weeks is defined as a best objective response of Complete Response (CR), Partial (PR) or stable disease (SD ≥ 24) per RECIST criteria (version 1.1) (MRI/CT scan every 8 weeks or sooner if clinically indicated).
    * Objective response rate defined as complete or partial response (CR or PR) per RECIST criteria (version 1.1) (MRI/CT scan every 8 weeks or sooner if clinically indicated)
    * Overall survival defined as the time elapsed between randomization and death from any cause
    * Event free survival defined as the time elapsed between randomization and disease progression, or treatment stop/delayed from toxicity reason, or death from any cause
    Patients who are alive without disease progression by the clinical cut-off will be censored at the dates of their last tumor evaluation.
    - Pharmacokinetic (PK) / pharmacodynamic parameters evaluation of ERY001 including
    * Pharmacokinetic parameters: Blood activity of free, total, plasmatic and encapsulated L-asparaginase
    * Pharmacodynamic parameters: Plasmatic concentrations of amino-acids (asparagine, aspartate, glutamine, and glutamate; ); Percentage of patient presenting with asparagine depletion at different time points (i.e. ≤ 2µM);
    * Percentage of deamination compared to baseline levels;
    * Immunogenicity: titers of Anti-L-asparaginase antibodies
    PK/PD parameters will be measured at different time points: prior each administration of ERY001 and then each day of chemotherapy administration. Anti-L asparaginase antibodies will be measured prior each administration of ERY001.
    - Tumor response evaluation by one or several tumor (bio)markers (CEA and CA 19.9) in different groups measured at baseline and at end of every 8 weeks of chemotherapy
    - Compliance to treatments: Ratio of performed/planned treatments injections over the total mean duration of treatment, ratio of performed/planned doses over the total duration of treatment.
    - Tumor response according ASNS level.
    - Patient quality of life measured by EORTC patient survey (QLQ-C30) with specific module Panc 26.

    Exploratory endpoints:
    - PFS rate of ASNS 2-3 patients with ERY001 at week 16;
    - KRAS mutational status;
    - Circulating tumor DNA quantification. Variations of circulating tumor DNA will be also correlated with radiological evaluations and clinical outcome
    - Genetic alterations within other frequently mutated genes in pancreatic cancer (SMAD4, P16);
    - To better define the tumor response by using new imaging methods such as diffusion and DCE MRI, CEUS and/or 18f-FDG PET, according to Chun and Choi criteria
    E.5.2.1Timepoint(s) of evaluation of this end point
    Timepoint(s) of evaluation of Secondary end points are described in E.5.2
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    standard polychemotherapy (FOLFOX4 or gemcitabine) without IMP
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned5
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    Definition is provided in the protocol and is defined as last patient / last visit
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 60
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 30
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state90
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 90
    F.4.2.2In the whole clinical trial 90
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Plans for treatment or care after the subject has ended his/her participation in the trial are not different from the expected normal treatment
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-02-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-01-23
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-11-07
    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-Thu Apr 25 20:03:28 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA