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    The EU Clinical Trials Register currently displays   36403   clinical trials with a EudraCT protocol, of which   5997   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2006-001489-17
    Sponsor's Protocol Code Number:SIOPENRNET003
    National Competent Authority:Greece - EOF
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2016-06-30
    Trial 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 ConcernedGreece - EOF
    A.2EudraCT number2006-001489-17
    A.3Full title of the trial
    High Risk Neuroblastoma Study 1.7 of SIOP-Europe (SIOPEN)
    R4 randomization for the use of the chimeric anti-GD2 antibody ch14.18
    Μελέτη Νευροβλαστώματος Υψηλού Κινδύνου 1.7 της SIOP-EUROPE (SIOPEN).
    Τυχαιοποίηση R4 για τη χρήση του χιμαιρικού αντι-GD2 αντισώματος ch14.18
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    High Risk Neuroblastoma Study
    Μελέτη Νευροβλαστώματος Υψηλού Κινδύνου
    A.3.2Name or abbreviated title of the trial where available
    HR-NBL-1.7/SIOPEN
    A.4.1Sponsor's protocol code numberSIOPENRNET003
    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 SponsorST. ANNA KINDERKREBSFORSCHUNG e.V.
    B.1.3.4CountryAustria
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportCHILDREN'S CANCER RESEARCH INSITUTE (CCRI)
    B.4.2CountryAustria
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCCRI
    B.5.2Functional name of contact pointIngrid PRIBILL
    B.5.3 Address:
    B.5.3.1Street AddressZimmermannplatz 10
    B.5.3.2Town/ cityWien
    B.5.3.3Post code1090
    B.5.3.4CountryAustria
    B.5.4Telephone number00431404704960
    B.5.5Fax number00431404707430
    B.5.6E-mailingrid.pribill@ccri.at
    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 numberP/0094/2014
    D.3 Description of the IMP
    D.3.1Product nameChimeric antibody ch14.18/CHO
    D.3.2Product code ch14.18/CHO
    D.3.4Pharmaceutical form Concentrate and solvent for solution for infusion
    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 INNch14.18/CHO
    D.3.9.1CAS number 1613303-02-8
    D.3.9.2Current sponsor codeAPN311
    D.3.9.3Other descriptive nameCH14.18
    D.3.9.4EV Substance CodeSUB130798
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4.5
    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 Yes
    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.IMP: 2
    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 Yes
    D.2.1.1.1Trade name Proleukin 18 x 10^6 IU
    D.2.1.1.2Name of the Marketing Authorisation holderNOVARTIS Pharma
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namealdesleukin
    D.3.4Pharmaceutical form Powder for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    Subcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAldesleukin
    D.3.9.1CAS number 110942-02-4
    D.3.9.3Other descriptive nameALDESLEUKIN
    D.3.9.4EV Substance CodeSUB05303MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1.1
    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.IMP: 3
    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 Yes
    D.2.1.1.1Trade name ETOPOSIDE/PHARMACHEMIE
    D.2.1.1.2Name of the Marketing Authorisation holderCHEMIPHARM S.G. DETSAVES & Co.
    D.2.1.2Country which granted the Marketing AuthorisationGreece
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameEtoposide
    D.3.4Pharmaceutical form Solution for infusion
    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 INNEtoposide
    D.3.9.1CAS number 117091642
    D.3.9.3Other descriptive nameETOPOSIDE PHOSPHATE
    D.3.9.4EV Substance CodeSUB13772MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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.IMP: 4
    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 Yes
    D.2.1.1.1Trade name PARAPLATIN
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers Squibb Hellas SA
    D.2.1.2Country which granted the Marketing AuthorisationGreece
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCarboplatine
    D.3.4Pharmaceutical form Solution for infusion
    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 INNCarboplatin
    D.3.9.1CAS number 41575-94-4
    D.3.9.3Other descriptive namePARAPLATIN
    D.3.9.4EV Substance CodeSUB06614MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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.IMP: 5
    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 Yes
    D.2.1.1.1Trade name CISPLATIN/HOSPIRA
    D.2.1.1.2Name of the Marketing Authorisation holderHOSPIRA UK LIMITED
    D.2.1.2Country which granted the Marketing AuthorisationGreece
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCISPLATIN
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    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 INNCISPLATIN
    D.3.9.1CAS number 15663-27-1
    D.3.9.3Other descriptive nameCISPLATIN
    D.3.9.4EV Substance CodeSUB07483MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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.IMP: 6
    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 Yes
    D.2.1.1.1Trade name ENDOXAN
    D.2.1.1.2Name of the Marketing Authorisation holderBAXTER HELLAS LTD
    D.2.1.2Country which granted the Marketing AuthorisationGreece
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCYCLOPHOSPHAMIDE
    D.3.4Pharmaceutical form Powder for solution 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 INNCYCLOPHOSPHAMIDE
    D.3.9.1CAS number 50-18-0
    D.3.9.3Other descriptive nameANHYDROUS CYCLOPHOSPHAMIDE
    D.3.9.4EV Substance CodeSUB121739
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500 to 1000
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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.IMP: 7
    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 Yes
    D.2.1.1.1Trade name DOXORUBIN
    D.2.1.1.2Name of the Marketing Authorisation holderCHEMIPHARM S.G. DETSAVES & Co.
    D.2.1.2Country which granted the Marketing AuthorisationGreece
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDOXORUBICINE
    D.3.4Pharmaceutical form Lyophilisate for solution for infusion
    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 INNDOXORUBICIN
    D.3.9.1CAS number 23214-92-8
    D.3.9.3Other descriptive nameADRIAMYCIN
    D.3.9.4EV Substance CodeSUB01827MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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.IMP: 8
    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 Yes
    D.2.1.1.1Trade name VINCRISTINE/PHARMACHEMIE
    D.2.1.1.2Name of the Marketing Authorisation holderCHEMIPHARM S.G. DETSAVES & Co.
    D.2.1.2Country which granted the Marketing AuthorisationGreece
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameVINCRISTINE
    D.3.4Pharmaceutical form Solution for injection/infusion
    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 INNVINCRISTINE
    D.3.9.1CAS number 2068-78-2
    D.3.9.3Other descriptive nameVCR
    D.3.9.4EV Substance CodeSUB05101MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1 to 2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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.IMP: 9
    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 Yes
    D.2.1.1.1Trade name BUSILVEX
    D.2.1.1.2Name of the Marketing Authorisation holderPIERRE FABRE MEDICAMENT
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameBUSULFAN
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    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 INNBUSULFAN
    D.3.9.1CAS number 55-98-1
    D.3.9.3Other descriptive nameBusulfex; Busulphan
    D.3.9.4EV Substance CodeSUB05993MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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.IMP: 10
    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 Yes
    D.2.1.1.1Trade name MELPHALAN
    D.2.1.1.2Name of the Marketing Authorisation holderASPEN PHARMA TRADING LTD
    D.2.1.2Country which granted the Marketing AuthorisationIceland
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameMELPHALAN
    D.3.4Pharmaceutical form Powder and solvent for solution for infusion
    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 INNMELPHALAN
    D.3.9.1CAS number 3223-07-2
    D.3.9.3Other descriptive nameMELPHALAN HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB126965
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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.IMP: 11
    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 Yes
    D.2.1.1.1Trade name HYCAMTIN
    D.2.1.1.2Name of the Marketing Authorisation holderNOVARTIS EUROPHARM LIMITED
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameHYCAMTIN
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    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 INNTOPOTECAN
    D.3.9.1CAS number 119413-54-6
    D.3.9.3Other descriptive nameTOPOTECAN HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB04921MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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.IMP: 12
    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 Yes
    D.2.1.1.1Trade name A-CNOTREN
    D.2.1.1.2Name of the Marketing Authorisation holderPHARMATHEN SACI
    D.2.1.2Country which granted the Marketing AuthorisationGreece
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameA-CNOTREN
    D.3.4Pharmaceutical form Capsule, soft
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNISOTRETINOIN
    D.3.9.1CAS number 4759-48-2
    D.3.9.3Other descriptive name13-cis RA
    D.3.9.4EV Substance CodeSUB08341MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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.IMP: 13
    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 Yes
    D.2.1.1.1Trade name GRANULOKINE
    D.2.1.1.2Name of the Marketing Authorisation holderAMGEN EUROPE B.V.
    D.2.1.2Country which granted the Marketing AuthorisationGreece
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameGRANULOKINE
    D.3.4Pharmaceutical form Solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFILGRASTIM
    D.3.9.1CAS number 121181-53-1
    D.3.9.3Other descriptive nameG-CSF
    D.3.9.4EV Substance CodeSUB07627MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.3
    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
    High Risk Neuroblastoma
    Yψηλού Κνδύνου Νευροβλάστωμα
    E.1.1.1Medical condition in easily understood language
    Neuroblastoma (the most common extracranial solid cancer in childhood and the most common cancer in infancy)
    Νευροβλάστωμα (το νευροβλάστωμα είναι ο συχνότερος εξωκρανιακός όγκος της παιδικής ηλικίας και ο συχνότερος καρκίνος της νεογνικής ηλικίας)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level PT
    E.1.2Classification code 10029260
    E.1.2Term Neuroblastoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To test the hypothesis that the modified N7 induction regimen will improve the metastatic response rates or event free survival (EFS) as compared to Rapid COJEC.
    • To test the hypothesis that the addition of subcutaneous aldesleukin (IL-2, (Proleukin®)) to immunotherapy with chimeric 14.18 anti-GD2 monoclonal antibody produced in Chinese hamster ovary (CHO) cells (ch14.18/CHO) given as continuous infusion in addition to differentiation therapy with isotretinoin (13-cis-RA) following myeloablative therapy (MAT) and autologous SCR, will improve EFS in patients with high-risk neuroblastoma (stage 4 disease or stages 2 and 3 with MYCN amplification all over the age of one, or infants with MYCN amplification).
    • Να ελεγχθεί η υπόθεση ότι η χημειοθεραπευτική αγωγή εφόδου με τροποποιημένο σχήμα Ν7 θα βελτιώσει τα ποσοστά ανταπόκρισης της μεταστατικής νόσου και την ελεύθερη της νόσου επιβίωση (EFS) σε σύγκριση με το χημειοθεραπευτικό σχήμα Rapid COJEC.
    • Να ελεγχθεί η υπόθεση πως η προσθήκη υποδόρια χορηγούμενης aldesleukin (IL-2, Proleukin®) στην ανοσοθεραπεία με χιμαιρικό μονοκλωνικό αντίσωμα 14.18 anti-GD2 που παράχθηκε σε κύτταρα ωοθηκών κινέζικου χάμστερ (CHO) (ch14.18/CHO) και που δίδεται ως συνεχής έγχυση, επιπρόσθετα της θεραπείας διαφοροποίησης με isotretinoin (13-cis-RA), έπειτα απο μυελοαφανιστική θεραπεία (ΜΑΤ) και αυτόλογο SCR, θα βελτιώσει την EFS σε ασθενείς με νευροβλάστωμα υψηλού κινδύνου (ασθενείς με νόσο σταδίου 4 ή σταδίου 2 και 3 με ενίσχυση του ογκογονιδίου MYCN και ηλικία μεγαλύτερη του ενός έτους, ή βρέφη με πολλαπλασιασμό MYCN).
    E.2.2Secondary objectives of the trial
    • To evaluate BM response to Rapid COJEC and modified N7 with ICH-GD2, AIPF and QRT-PCR.
    • To evaluate response to Rapid COJEC and modified N7 induction therapies with mIBG for standardised scoring of skeletal response.
    • To determine the effect of response of metastatic disease to induction therapy on EFS and OS
    • To investigate the relationship between complete surgical resection of the primary tumour and OS.
    • To collect data on selected, validated biological features and to determine the effect of these on EFS, the incidence of relapse/progression and OS.
    • To compare the toxicity, in particular episodes of febrile neutropenia and grade 3-4 infection, associated with induction therapy with Rapid COJEC and modified N7.
    • To sample PK data to calculate the effect of AUC as achieved according to dosing guidelines.
    • To monitor drug levels of MAT and relate them to patients outcome and toxicity.
    • Να αξιολογηθεί η ανταπόκριση του μυελού των οστών στο σχήμα εφόδου Rapid COJEC και στο τροποποιημένο σχήμα εφόδου Ν7 με ICH-GD2, AIPF και QRT-PCR.
    • Να αξιολογηθεί η ανταπόκριση στη θεραπεία με Rapid COJEC & τροποπ. Ν7, με mIBG σε τυποποιημένη βαθμολόγηση της σκελετικής ανταπόκρισης.
    • Να καθοριστεί το αποτέλεσμα της θεραπείας εφόδου στην EFS και την OS.
    • Να διερευνηθεί η σχέση μεταξύ πλήρους χειρουργικής εκτομής του πρωτογενούς όγκου και OS.
    • Να συλλεχθούν δεδομένα σε επιλεγμένα, έγκυρα βιολογικά χαρακτηριστικά και να καθοριστεί το αποτέλεσμα τους στην EFS, τη συχνότητα των υποτροπιών και την OS.
    • Να συγκριθεί η τοξικότητα σε συγκεκριμένα επεισόδια εμπύρετης ουδετεροπενίας και λοιμώξεις 3-4 βαθμού σχετιζόμνες με θεραπεία εφόδου.
    • Να συλλεχθούν φαρμακοκινητικά (PK) δεδομένα για τον υπολογισμό της AUC, όπως αυτή επετεύχθη σύμφωνα με τις οδηγίες δοσολογίας.
    • Να μετρηθούν τα επίπεδα των φαρμάκων της ΜΑΤ και η σχέση τους με έκβαση ασθενών και τοξικότητα.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Established diagnosis of neuroblastoma according to the International Neuroblastoma
    Staging System (INSS).
    • Age below 21 years.
    • High risk neuroblastoma defined as either:
    a) INSS stage 2, 3, 4, and 4s with MYCN amplification, or
    b) INSS stage 4 without MYCN amplification aged > 12 months at diagnosis
    • Patients who have received no previous chemotherapy except for one cycle of etoposide and carboplatin (VP16 / Carbo). In this situation patients will receive Rapid COJEC induction and the first Rapid COJEC cycle may be replaced by the first cycle VP16/Carbo (etoposide / carboplatin).
    • Written informed consent, including agreement of parents or legal guardian for minors, to enter a randomised study if the criteria for randomisation are met.
    • Tumour cell material available for determination of biological prognostic factors.
    • Females of childbearing potential must have a negative pregnancy test. Patients of childbearing potential must agree to use an effective birth control method. Female patients who are lactating must agree to stop breast-feeding.
    • Registration of all eligibility criteria with the data centre within 6 weeks from diagnosis.
    • Provisional follow up of 5 years.
    • Επιβεβαιωμένη διάγνωση νευροβλαστώματος σύμφωνα με το Διεθνές Σύστημα Σταδιοποίησης Νευροβλαστώματος (International Neuroblastoma Staging System INSS)
    • Ηλικία κάτω των 21 ετών
    • Το νευροβλάστωμα υψηλού κινδύνου ορίζεται ως:
    α) INSS σταδίου 2, 3, 4 και 4 με πολλαπλασιασμό του MYCN, ή
    β) INSS σταδίου 4 χωρίς πολλαπλασιασμό του MYCN με ηλικία > 12 μηνών κατά τη διάγνωση.
    • Ασθενείς που δεν έχουν λάβει προηγουμένως χημειοθεραπεία παρά μόνο έναν κύκλο ετοποσίδης και καρβοπλατίνης (VP16 / Carbo). Σε αυτές τις περιπτώσεις οι ασθενείς θα λάβουν σχήμα εφόδου Rapid COJEC και ο πρώτος κύκλος Rapid COJEC μπορεί να αντικατασταθεί απο VP16 / Carbo (ετοποσίδη / καρβοπλατίνη).
    • Έντυπο συγκατάθεσης ασθενούς μετά από ενημέρωση, που περιλαμβάνει συγκατάθεση των γονέων ή του νόμιμου κηδεμόνα για τους ανήλικους, για την συμμετοχή σε τυχαιοποιημένη μελέτη, υπό τη προϋπόθεση ότι θα πληρούνται τα κριτήρια τυχαιοποίησης.
    • Διαθέσιμο υλικό καρκινικών κυττάρων για τον καθορισμό βιολογικών προγνωστικών παραγόντων.
    • Γυναίκες με δυνατότητα τεκνοποίησης πρέπει να έχουν ένα αρνητικό τέστ κυήσεως. Ασθενείς με δυνατότητα τεκνοποίησης πρέπει να συγκατατεθούν να χρησιμοποιούν αποτελεσματική μέθοδο αντισύλληψης. Γυναίκες που θηλάζουν πρέπει να συγκατατεθούν να διακόψουν το θηλασμό.
    • Καταχώρηση όλων των στοιχείων επιλεξιμότητας στο Κέντρο Δεδομένων Μελέτης εντός 6 εβδομάδων απο τη διάγνωση.
    • Ενδεχόμενο παρακολούθησης εως 5 έτη.
    E.4Principal exclusion criteria
    Any negative answer concerning the inclusion criteria of the study, R3 or R4 will render the patient ineligible for the corresponding therapy phase.
    Οποιαδήποτε αρνητική απάντηση σχετικά με τα κριτήρια ένταξης της μελέτης, R3 ή R4, καθιστούν τον/την ασθενή μη επιλέξιμο για την αντίστοιχη φάση θεραπείας.
    E.5 End points
    E.5.1Primary end point(s)
    Randomization 3:
    Two co-primary endpoints will be investigated:
    1) Metastatic Response after induction treatment
    • No skeletal uptake on MiBG
    • Negative bone marrow aspirates and trephines
    • Αbsence of other metastatic sites
    2) Event Free Survival (EFS)
    • disease progression or relapse
    • death from any cause
    • second neoplasm

    Randomization 2: Imunnotherapy - Question Ch14/18/CHO with or without aldesleukin (IL-2)

    Primary endpoint: 3-year EFS calculated from the date of the second randomization.
    The following will be considered as events:
    • disease progression
    • death from any cause
    • second neoplasm
    Tυχαιοποίηση 3:
    Δύο συμπρωταρχικά καταληκτικά σημεία θα διερευνηθούν:
    1) Η ανταπόκριση των μεταστάσεων μετά τη χημειοθεραπεία εφόδου
    • Απουσία σκελετικής πρόσληψης στο MiBG
    • Αρνητικά δείγματα αναρρόφησης ή τρυπανισμού του μευλού των οστών
    • Απουσία άλλων εστιων μετάστασης
    2) Ελεύθερη Συμβάντων Επιβίωση (EFS)
    • Εξέλιξη ή υποτροπή της νόσου
    • Θάνατος από οποιαδήποτε αιτία
    • Δεύτερη νεολασία

    Τυχαιοποίηση 2: Ανοσοθεραπεία - συμβολή του Ch14/18/CHO με ή χωρίς αλδεσλευκίνη (IL-2)

    Κύριο Καταληκτική Σημείο: 3 ετής Επιβίωση Ελεύθερη Συμβάντων (EFS), υπολογιζόμενη από την ημερομηνία της δεύτερης τυχαιοποίησης
    Τα ακόλουθα θα θεωρούνται ως συμβάντα:
    • Εξέλιξη ή υποτροπή της νόσου
    • Θάνατος από οποιαδήποτε αιτία
    • Δεύτερη νεολασία
    E.5.1.1Timepoint(s) of evaluation of this end point
    The final analysis will be performed 18 months from R1 and R2 and 6 months from R3, after the inclusion of the last patient
    Η τελική ανάλυση θα πραγματοποιηθεί 18 μήνες μετά την τυχαιοποίηση R1 και R2 και 6 μήνες μετά την τυχαιοποίηση R3, μετά την ένταξη του τελευταίου ασθενούς
    E.5.2Secondary end point(s)
    • Overall Survival (calculated from the date of randomization to the death from any cause)
    • Cumulative incidence of disease relapse/progression and deaths without relapse/progression
    • Cumulative incidence of treatment-related mortality and of disease-related mortality
    • Response [Overall Response (incl. primary tumor after induction0, skeletal response on MiBG, BM response]
    • Toxicity (in particular, comparison of the frequency of episodes of FNP and Grade 3-4 infections during induction treatments [modified N7 vs. COJEC)
    • Response rates, survival, EFS and the cumulative incidence of relapse/progression will be related to prognostic factors inc.: biological factors [MYCN amplification, SCAs, expression signature] of the neuroblastoma cells in the bone marrow and/or the primary tumor
    • Serological factors (serum concentrations at diagnosis of LDH, ferritin, neuron specific enolase)
    • Urinary catecholamines at diagnosis (VMA, HVA, dopamine)
    • Συνολική Επιβίωση (υπολογιζόμενη από την ημερομηνία τυχαιοποίησης έως την ημερομηνία θανάτου, από οποιαδήποτε αιτία)
    • Αθροιστική επίπτωση των υποτροπών/της εξέλιξης της νόσου και των θανάτων απουσία υποτροπής/εξέλιξης της νόσου.
    • Αθροιστική επίπτωση της σχετιζόμενης με τη θεραπεία θνητότητας και της σχετιζόμενης με τη νόσο θνητότητας.
    • Ανατπόκριση [Συνολική Ανταπόκριση (συμπεριλ. την ανταπόκριση του πρωτοπαθούς όγκου μετά τη χημειοθεραπεία εφόδου), την σκελετική ανατπόκριση στη MiBG, την ανταπόκριση του μευλού των οστών]
    • Τοξικότητα (ειδικότερα, σύγκριση της συχνότητας των επεισοδίων εμπύρετης ουδετεροπενίας και Βαθμού 3-4 λοιμώξεων στη διάρκεια της χημειοθεραεπίας εφόδου [τροποποιημένο σχήμα N7 vs. COJEC)
    • Τα ποσοστά ανταπόκρισης, τα ποσοστά επιβίωσης και EFS και η αθροιστική επίπτωση υποτροπών/περιπτώσεων εξέλιξης της νόσου θα συσχετιστούν με προγνωστικούς παράγοντες [ενίσχυση του ογκογονιδίου MYCN, SCAs) των κυττάρων του νευροβλαστώματις στο μυελό των οστών ή/κσι στον προωτοπαθή όγκο.
    • Ορολογικοί παράγοντες (συγκεντρώσεις πλάσματος κατά τη διάγνωση των LDH, φερριτίνης, ειδικής κυτταρικής ενδολάσης)
    •Κατεχολαμίνες ούρων κατά τη διάγνωση (VMA, HVA, ντοπαμίνη)
    E.5.2.1Timepoint(s) of evaluation of this end point
    The final analysis will be performed 18 months from R1 and R2 and 6 months from R3, after the inclusion of the last patient
    Η τελική ανάλυση θα πραγματοποιηθεί 18 μήνες μετά την τυχαιοποίηση R1 και R2 και 6 μήνες μετά την τυχαιοποίηση R3, μετά την ένταξη του τελευταίου ασθενούς
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 No
    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
    Xημειοθεραπεία εφόδου Rapid COJEC
    Induction chemotherapy Rapid COJEC
    E.8.2.4Number of treatment arms in the trial4
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA120
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Austria
    Belgium
    Czech Republic
    Denmark
    Finland
    France
    Greece
    Hungary
    Ireland
    Israel
    Italy
    Norway
    Poland
    Portugal
    Serbia
    Slovakia
    Spain
    Sweden
    Switzerland
    United Kingdom
    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
    Τhe final analysis will be performed 18 months after the inclusion of the last patient.

    To evaluate the difference of EFS between the randomized arms, all randomized patients will be analyzed and the comparison of treatment regimens will be performed on the ITT population.

    The 3-year EFS will be estimated by the Kaplan-Meier method.
    H τελική ανάλυση θα πραγματοποιηθεί 18 μήνες μετά την ένταξη του τελευταίου ασθενούς

    Προκειμένου να αξιολογηθεί η διαφορά των EFS μεταξύ των τυχαιοποιημένων θεαπευτικών σκελών της μελέτης, όλοι οι τυχαιοποιημένοι ασθενείς θα ναλυθούν και η σύγκριση μεταξύ των τυχαιοποιημένων θεραπευτικών σχημάτων θα πραγματοποιηθεί στον πληθυσμό ITT.

    Η τριετής επιβίωση EFS θα υπολογιστεί με τη μέθοδο των Kaplan-Meier.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years7
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 2700
    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) Yes
    F.1.1.4.1Number of subjects for this age range: 530
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 2110
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 60
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Children
    Παιδιατρικοί ασθενείς
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 2500
    F.4.2.2In the whole clinical trial 2700
    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)
    Patients are enrolled in a 5-year follow-up period.
    No further treatment planned
    Oι ασθενείς θα εντάσσονται σε ένα 5-ετές πρόγραμμα παρακολούθησης.
    Δεν έχει προγραμματιστεί καμία επιπλέον θεραπεία
    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 Decision2016-08-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-07-26
    P. End of Trial
    P.End of Trial StatusOngoing
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