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 are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   38143   clinical trials with a EudraCT protocol, of which   6264   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).
     
    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:2011-004062-15
    Sponsor's Protocol Code Number:RIST-rNB-2011
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2012-04-16
    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 ConcernedGermany - BfArM
    A.2EudraCT number2011-004062-15
    A.3Full title of the trial
    Prospective, open label, randomized phase II trial to assess a multimodal molecular targeted therapy in children, adolescent and young adults with relapsed or refractory high risk neuroblastoma
    Prospektive, randomisierte, open-label Phase II-Studie zur Untersuchung der Wirksamkeit einer multimodalen molekular basierten Therapie bei Kindern, Jugendlichen und jungen Erwachsenen mit rezidiviertem oder therapierefraktärem Neuroblastom
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A randomized clinical study to investigate the efficiency of a novel anti-cancer medication against neuroblastoma in children, adolescent and young adults in whom the tumor relapsed or was refractory to standard care
    Eine klinische Untersuchung zur Überprüfung einer gegen Tumorwachstums-Mechanismen abzielenden Therapie für rückfällig gewordene beziehungsweise auf die Standardtherapie nicht mehr ansprechende Patienten mit Neuroblastom, dem häufigsten Tumor im Kleinkindesalter.
    A.3.2Name or abbreviated title of the trial where available
    RIST-rNB-2011
    A.4.1Sponsor's protocol code numberRIST-rNB-2011
    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 SponsorUniversity Hospital of Regensburg
    B.1.3.4CountryGermany
    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 supportMedac GmbH
    B.4.2CountryGermany
    B.4.1Name of organisation providing supportDeutsche Krebshilfe (DKH)
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Hospital of Regensburg
    B.5.2Functional name of contact pointSPOH Dokumentation
    B.5.3 Address:
    B.5.3.1Street AddressFranz-Josef-Strauss-Allee 11
    B.5.3.2Town/ cityRegensburg
    B.5.3.3Post code93053
    B.5.3.4CountryGermany
    B.5.4Telephone number00490941944 2063
    B.5.5Fax number00490941944 2068
    B.5.6E-mailspoh@ukr.de
    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 Yes
    D.2.1.1.1Trade name Sprycel
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers-Squibb
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameSprycel
    D.3.4Pharmaceutical form Film-coated tablet
    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 INNDASATINIB
    D.3.9.1CAS number 302962-49-8
    D.3.9.4EV Substance CodeSUB23322
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Temomedac®
    D.2.1.1.2Name of the Marketing Authorisation holderMedac
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameTemomedac
    D.3.4Pharmaceutical form Capsule, hard
    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 INNTEMOZOLOMIDE
    D.3.9.1CAS number 85622-93-1
    D.3.9.4EV Substance CodeSUB10889MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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: 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 Rapamune
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Ltd
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameRapamune
    D.3.2Product code PF-00835135
    D.3.4Pharmaceutical form Oral solution
    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 INNSIROLIMUS
    D.3.9.1CAS number 53123-88-9
    D.3.9.3Other descriptive nameRapamycin
    D.3.9.4EV Substance CodeSUB10537MIG
    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 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 Yes
    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 RoleComparator
    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 Irinomedac
    D.2.1.1.2Name of the Marketing Authorisation holderMedac
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameIrinomedac
    D.3.2Product code Medac
    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 INNIRINOTECAN
    D.3.9.1CAS number 97682-44-5
    D.3.9.4EV Substance CodeSUB08295MIG
    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: 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 Rapamune
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameRapamune
    D.3.2Product code PF-00835135
    D.3.4Pharmaceutical form Tablet
    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 INNSIROLIMUS
    D.3.9.1CAS number 53123-88-9
    D.3.9.3Other descriptive nameRapamycin
    D.3.9.4EV Substance CodeSUB10537MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 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 Yes
    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 Sprycel
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers-Squibb
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameSprycel
    D.3.4Pharmaceutical form Film-coated tablet
    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 INNDASATINIB
    D.3.9.1CAS number 302962-49-8
    D.3.9.4EV Substance CodeSUB23322
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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: 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 Sprycel
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers-Squibb
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameSprycel
    D.3.4Pharmaceutical form Film-coated tablet
    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 INNDASATINIB
    D.3.9.1CAS number 302962-49-8
    D.3.9.4EV Substance CodeSUB23322
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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: 8
    D.1.2 and D.1.3IMP RoleComparator
    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 Temomedac®
    D.2.1.1.2Name of the Marketing Authorisation holderMedac
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameTemomedac
    D.3.4Pharmaceutical form Capsule, hard
    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 INNTEMOZOLOMIDE
    D.3.9.1CAS number 85622-93-1
    D.3.9.4EV Substance CodeSUB10889MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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: 9
    D.1.2 and D.1.3IMP RoleComparator
    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 Temomedac®
    D.2.1.1.2Name of the Marketing Authorisation holderMedac
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameTemomedac
    D.3.4Pharmaceutical form Capsule, hard
    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 INNTEMOZOLOMIDE
    D.3.9.1CAS number 85622-93-1
    D.3.9.4EV Substance CodeSUB10889MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 RoleComparator
    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 Temomedac®
    D.2.1.1.2Name of the Marketing Authorisation holderMedac
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameTemomedac
    D.3.4Pharmaceutical form Capsule, hard
    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 INNTEMOZOLOMIDE
    D.3.9.1CAS number 85622-93-1
    D.3.9.4EV Substance CodeSUB10889MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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 Rapamune
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameRapamune
    D.3.2Product code PF-00835135
    D.3.4Pharmaceutical form Tablet
    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 INNSIROLIMUS
    D.3.9.1CAS number 53123-88-9
    D.3.9.3Other descriptive nameRapamycin
    D.3.9.4EV Substance CodeSUB10537MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 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 Yes
    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 Rapamune
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameRapamune
    D.3.2Product code PF-00835135
    D.3.4Pharmaceutical form Tablet
    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 INNSIROLIMUS
    D.3.9.1CAS number 53123-88-9
    D.3.9.3Other descriptive nameRapamycin
    D.3.9.4EV Substance CodeSUB10537MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 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 Yes
    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 Rapamune
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Ltd.
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameRapamune
    D.3.2Product code PF-00835135
    D.3.4Pharmaceutical form Tablet
    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 INNSIROLIMUS
    D.3.9.1CAS number 53123-88-9
    D.3.9.3Other descriptive nameRapamycin
    D.3.9.4EV Substance CodeSUB10537MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 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 Yes
    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: 14
    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 Sprycel
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers-Squibb
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameSprycel
    D.3.4Pharmaceutical form Film-coated tablet
    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 INNDASATINIB
    D.3.9.1CAS number 302962-49-8
    D.3.9.4EV Substance CodeSUB23322
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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: 15
    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 Sprycel
    D.2.1.1.2Name of the Marketing Authorisation holderBristol-Myers-Squibb
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameSprycel
    D.3.4Pharmaceutical form Film-coated tablet
    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 INNDASATINIB
    D.3.9.1CAS number 302962-49-8
    D.3.9.4EV Substance CodeSUB23322
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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.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
    Relapsed or refractory high risk neuroblastoma
    Rezidiviertes oder therapierefraktäres Neuroblastom

    E.1.1.1Medical condition in easily understood language
    Relapsed or refractory high risk neuroblastoma

    Neuroblastom, das wiederaufgetreten ist/nicht auf die Ersttherapie angeschlagen hat

    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    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 trial is the evaluation of progression-free survival of rNB in children, adolescents and young adults, comparing a multimodal treatment regimen consisting of temozolomide (T), irinotecan (I), rapamycin (R) and dasatinib (S) against Irinotecan (I)/Temozolomide (T) alone.
    Das primäre Studienziel ist die Evaluation des progressionsfreien Überlebens (PFS) von Kindern, Jugendlichen und jungen Erwachsenen mit rezidivierten Hochrisiko-Neuroblastomen (rNB), durch die Gegenüberstellung eines multimodalen Behandlungsregimes bestehend aus Temozolomid (T), Irinotecan (I), Sirolimus (R) und Dasatinib (S) und Irinotecan (I)/Temozolimid (T) allein.
    E.2.2Secondary objectives of the trial
    Secondary objectives are
    • Overall survival
    • Response rate (RR) after 4 and 8 courses of irinotecan and temozolomide in the RIST treatment arm
    • Toxicity of this combination of drugs in children, adolescents and young adults with rNB
    • Duration of response of this treatment regimen
    • Safety and tolerability of the investigational treatment
    • Assessment of quality of life
    • Assessment of the prognostic relevance of the International Neuroblastoma Risk Group (INRG) classification system on the event free survival
    • Prognostic relevance of defined factors on the event free survival in this patient population (i.e. response assessment of HVA, VMA, NSE)
    Sekundäre Ziele sind:
    •Gesamtüberleben (OS)
    •Response Rate (RR) nach 4 und 8 Kursen Irinotecan und Temozolomid im RIST-Behandlungsarm
    •Evaluation der Toxizitäten dieser Arzneimittel-Kombination bei Kindern, Jugendlichen und jungen Erwachsenen mit rNB
    •Ansprechdauer des RIST Behandlungsregimes
    •Sicherheit und Verträglichkeit des RIST-Behandlungsregimes
    •Bewertung der Lebensqualität
    • Beurteilung der prognostischen Relevanz des International Neuroblastoma Group (INRG) Klassifikation-Systems auf das EFS
    •Prognostische Relevanz von definierten Faktoren auf das ereignisfreie Überleben dieser Patientenpopulation (d. h. Ansprechen von HVA, VMA, NSE)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patients with relapsed high-risk neuroblastoma (stage IV and all MYCN pos. stages) or progressive disease during primary treatment (=rNB) / Patients with relapsed
    and all of the following criteria will be considered for admission to the clinical trial:
    • Children, adolescents and young adults 0 months to 25 years
    • Signed written informed consent (patient or his/her parents/legal guardian)
    • Females of childbearing age must have a negative urine pregnancy test prior to starting the study drug. The first pregnancy test must be performed within 10-14 days prior to the start of the study drug and the second pregnancy test must be performed within 24 hours prior to the start of study drug. The subject may not receive the study drug until the investigator has verified that the results of these pregnancy tests are negative.
    • Females of childbearing age must comply with the institutional standards of birth control with a pearl index <1%. Contraception must be started at least four weeks before the start of the investigational therapy.
    • Females of childbearing age must be willing to abstain from breastfeeding for the duration of the clinical trial and for at least 30 days after discontinuation of the clinical trial.
    • Males must agree not to father a child and must use latex condom during any sexual contact with women of childbearing age during and for 6 months after therapy ends or is stopped, even if they have undergone successful vasectomy.
    • Willing and able to complete the clinical trial procedures, as described in the protocol
    • Non-smoker for at least the previous 3 months. Smoking is not allowed during the entire study period
    • Abstain from alcohol within the last 24 hours before screening and before admission to the clinical trial center as well as during the entire clinical trial. The regular daily ethanol intake has to be less than 20g/day for at least the previous three months.
    • Patients are required to have an absolute neutrophil count (ANC) ≥500/µL, hemoglobin ≥8g/dL (transfusion permitted), and an unsupported platelet count ≥30,000/µL unless:
    - extensive bone marrow involvement was documented
    - patient is refractory or relapsed early after primary therapy
    Patienten mit rezidiviertem Hochrisiko-Neuroblastom (Stadium IV und alle anderen Stadien mit N-MYC pos. Neuroblastom) oder progrediente Erkrankung während Ersttherapie (=rNB)
    die alle folgenden Kriterien erfüllen:
    •Kinder, Jugendliche und junge Erwachsene jünger als 25 Jahre
    •Vorliegen einer unterschriebenen Einverständniserklärung zur Teilnahme an der Studie
    •Negativer Schwangerschaftstest vor Einnahme der Studienmedikation bei weiblichen Studienteilnehmern in gebärfähigem Alter. Ein erster Schwangerschaftstest sollte 10-14 Tage vor Beginn der Einnahme der Studienmedikation erfolgen. Der zweite Test muss innerhalb von 24 Std. vor Einnahme der Studienmedikation erfolgen. Ein Erhalt der Studienmedikation erfolgt erst nach Überprüfung des Prüfarztes auf Nichtvorliegen einer Schwangerschaft.
    •Weibliche Studienteilnehmer müssen eine Methode zur Empfängnisverhütung mit einem Pearl-Index von <1% anwenden. Der Beginn dieser Empfängnisverhütung muss mindestens 4 Wochen vor der ersten Einnahme der Studienmedikation erfolgen.
    •Frauen in gebärfähigem Alter dürfen während der gesamten Studiendauer bis einschließlich 30 Tage nach Studiendauer nicht stillen.
    •Männliche Studienteilnehmer müssen zustimmen, während der Laufzeit der Studie und bis 6 Monate nach Beendigung der Studientherapie, kein Kind zu zeugen und Latex-Kondome bei jedem sexuellen Kontakt mit Frauen in gebärfähigem Alter zu benutzen. Dies gilt auch, wenn eine erfolgreiche Vasektomie durchgeführt wurde.
    •Bereitschaft des Patienten dem Behandlungsplan protokollgemäß zu nachzukommen.
    •Nichtraucher für mindestens 3 Monate vor Beginn der Studientherapie. Rauchen ist während der gesamten Studientherapie nicht erlaubt.
    •Kein Alkoholgenuss innerhalb der letzten 24 Stunden vor Screening und Aufnahme in das Prüfzentrum ebenso während der gesamten klinischen Studie. Während der vorangegangenen drei Monate sollte der Alkoholkonsum 20g/Tag nicht überschritten haben.
    •Absolute Neutrophilenzahl (ANC) ≥ 500/ µL, Hb ≥8 g/dL (Transfusion erlaubt) und Thrombozytenzahl (ohne Transfusion) ≥30,000/µL es sei denn:
    - ein ausgedehnter Knochenmarksbefall liegt vor
    - der Patient ist therapierefraktär auf Ersttherapie oder es liegt ein Frührezidiv nach Ersttherapie vor.

    E.4Principal exclusion criteria
    Patients presenting with any of the following criteria will not be included in this clinical trial:
    • Pregnancy, nursing
    • Patients who suffered from a thrombotic event and need anticoagulation (i.e. coumadine derivatives or low molecular weight heparin derivatives, LMWH)
    • Patients with cardiac arrhythmias especially prolonged QT
    • Patients with chronic inflammatory bowel diseases and/or bowel obstruction
    • Patients with bilirubin serum levels 1,5 fold above the upper normal limit
    • Vaccination with a live virus vaccine during the clinical trial
    • Impaired liver function and/or impaired renal function (hepatic and renal index parameter two times above normal range; see below)
    • Potentially unreliable subjects, probably non compliant subjects and those judged by the investigator to be unsuitable for the study
    • Doubts about the patient’s cooperation
    • Any contraindications or known hypersensitivity to the IMPs or to any of the other components: (see SPC ”Fachinformation”)
    • Known allergic reactions to the treatment medication
    • Patients who were treated with radiation and/or chemotherapy for any other oncological condition
    • Participation in any other interventional phase I to III trial
    • Sexually active patients who refuse to use contraception according to the institutional requirements
    • Patients with extremely poor general condition (Karnofsky or Lansky score <50%)
    • Neutrophil count (ANC) <500/µL, hemoglobin <8g/dL (transfusion permitted), and an unsupported platelet count <30 000/µL
    • 12-lead ECG with QTc>500 msec / QTc>60 msec baseline
    - Patients with hepatitis B reactivation

    Patienten, die eines der folgenden Kriterien erfüllen, werden nicht in die klinische Studie eingeschlossen:
    •Schwangerschaft, Stillzeit
    •Patienten mit thrombotischen Ereignissen und die aufgrund dessen Antikoagulantien (d.h. Coumarin-Derivate oder niedermolekulares Heparin, LMWH) erhielten
    •Patienten, die unter Arrhythmien leiden, besondere eine verlängerte QT-Zeit aufweisen
    •Patienten mit chronisch entzündlichen Darmerkrankungen und/oder Darmverschluss
    •Patienten, deren Bilirubin-Serumspiegel dreimal höher als der Normwert ist
    •Impfung mit Lebendviren während der Laufzeit der Studie
    •Beeinträchtigte Leberfunktion und/oder gestörte Nierenfunktion (Leber- und Nierenwerte zweimal über Normwert, siehe unten)
    •Personen mit mangelnder Compliance und die vom Prüfer als nicht zulässig für die Studie beurteilt wurden
    •Bei Zweifeln über die Kooperation des Patienten
    •Alle die Prüfmedikamente oder irgendeinen der anderen Inhaltsstoffe (siehe beigefügte Fachinformation) betreffende Kontraindikationen oder bekannte Überempfindlichkeiten
    •Bekannte allergische Reaktion auf die verabreichten Medikation
    •Patienten, die bereits aufgrund anderer onkologischer Vorerkrankung mit Chemotherapie und/oder Strahlentherapie vorbehandelt sind
    •Teilnahme an einer anderen interventionellen Studie der Phasen I bis III
    •Sexuell aktive Menschen, die sich einer effektiven Kontrazeption verweigern
    •Patienten mit sehr schlechtem klinischen Allgemeinzustand (Karnofsky oder Lansky Scores <50%)
    •Absolute Neutrophilenzahl (ANC) <500/ µL, Hb <8 g/dL (Transfusion erlaubt) und Thrombozytenzahl (ohne Transfusion) <30,000/µL
    •12-Kanal-EKG mit einer QTc>500 msec / QTc>60 msec baseline
    - Patienten mit Hepatitis-B Reaktivierung
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is progression-free survival (PFS), which is defined as the time interval between randomization and date of progression (first time at which progression can be declared) according to
    • Imaging criteria
    (MRI, MIBG. CT, US)
    and/or
    • Bone marrow morphology or
    • date of death of any cause

    Patients with no progression until end of study or patients lost to follow up will be classified as censored cases at the latest date they will be confirmed to be progression free.


    Der primäre Endpunkt ist progressionsfreies Überleben, definiert als das Zeitintervall zwischen Behandlungsbeginn und Progressionsdatum, entsprechend
    •Bildgebenden Kriterien (MRT, MIBG, CT, US)
    und/oder
    •Knochenmarkmorphologie oder
    •Todeszeitpunkt jeglicher Ursache
    Patienten ohne Progress bis Studienende oder Patienten, die lost-to-follow-up sind, werden als zensierte Fälle ab dem Datum bewertet, an dem Progressionsfreiheit bestätigt wurde
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoint of this study, progression free survival will be investigated after after 8 completed I/T-courses (approximately 20 weeks). The patients are then followed in 3-monthly intervals until one year after medical treatment was finished.
    Der Primäre Endpunkt der Studie, das Progressions-freie Überleben, wird nach 8 vollendeten I/T-Kursen (ca. 20 Wochen) beurteilt. Anschließend erfolgt eine Nachbeobachtung in vierteljährlichem Abstand bis ein Jahr nach Ende der Therapie.
    E.5.2Secondary end point(s)
    •Overall survival (OS)
    •Response to the investigational treatment after 4 and 8 courses of I/T and 1-year-follow-up in the RIST treatment arm
    •Duration until adequate response to this treatment regimen
    •Assessment of quality of life (Lansky and Karnofsky Scores)
    •Remission or stable disease according to laboratory parameters (HVA,VMA, NSE, LDH)
    •Evaluation of the prognostic relevance of MIBG scintigraphy
    •Gesamtüberleben (OS)
    •Therapieansprechen nach 4 und 8 Kursen I/T und 1 Jahr Follow-Up im RIST-Arm
    •Dauer bis zum Therapieansprechen in diesem Therapieregime
    •Bewertung der Lebensqualität (Lansky und Karnofsky Scores)
    •Remission oder ‚stable disease’ entsprechend Laborparametern (HVA, VMA, NSE, LDH)
    •Evaluation der prognostischen Relevanz der MIBG scintigraphie
    E.5.2.1Timepoint(s) of evaluation of this end point
    - after 4 completed I/T-courses (8 weeks), after 8 completed I/T-courses (20 weeks) and in 3-monthly intervals until one year after medical treatment was finished.
    - quality of life will be investigated before start of treatment and then in 6-monthly intervals until one year after medical treatment was finished.
    - nach 4 vollendeten I/T-Kursen (8 Wochen), nach 8 vollendeten I/T-Kursen (20 Wochen) und anschließend in vierteljährlichem Abstand bis ein Jahr nach Ende der Therapie beurteilt.
    die Lebensqualität, wird vor Beginn der Therapie und nachfolgend in halbjährlichem Abstand bis 1 Jahr nach Ende der Therapie beurteilt.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    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 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) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    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 concerned40
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA45
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months8
    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 Yes
    F.1.1Number of subjects for this age range: 130
    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: 22
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 90
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 2
    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 under the age of comprehension of the trial and therefore unable to give sonsent or even assent
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state114
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 114
    F.4.2.2In the whole clinical trial 114
    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 in the trial are followed according to the guidelines of the GPOH (German Pediatric Oncology Group) for 10 years outlined in the protocol.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Gesellschaft für pädiatrische Onkologie und Hämatologie
    G.4.3.4Network Country Germany
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-08-06
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-07-04
    P. End of Trial
    P.End of Trial StatusCompleted
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA