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   37219   clinical trials with a EudraCT protocol, of which   6124   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:2011-004868-30
    Sponsor's Protocol Code Number:PNET5MB
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2014-01-09
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2011-004868-30
    A.3Full title of the trial
    AN INTERNATIONAL PROSPECTIVE STUDY ON CLINICALLY STANDARD-RISK MEDULLOBLASTOMA IN CHILDREN OLDER THAN 3 TO 5 YEARS WITH LOW-RISK BIOLOGICAL PROFILE (PNET 5 MB - LR) OR AVERAGE-RISK BIOLOGICAL PROFILE (PNET 5 MB -SR)
    AN INTERNATIONAL PROSPECTIVE STUDY ON CLINICALLY STANDARD-RISK MEDULLOBLASTOMA IN CHILDREN OLDER THAN 3 TO 5 YEARS WITH LOW-RISK BIOLOGICAL PROFILE (PNET 5 MB - LR) OR AVERAGE-RISK BIOLOGICAL PROFILE (PNET 5 MB -SR)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Lo studio è stato pensato per pazienti affetti da un tumore cerebrale (il medulloblastoma) e che abbiano età superiore a 3 anni, asportazione chirurgica completa o quasi completa del tumore e assenza di metastasi alla diagnosi.
    Lo studio è stato pensato per pazienti affetti da un tumore cerebrale (il medulloblastoma) e che abbiano età superiore a 3 anni, asportazione chirurgica completa o quasi completa del tumore e assenza di metastasi alla diagnosi.
    A.3.2Name or abbreviated title of the trial where available
    SIOP PNET 5 MB
    SIOP PNET 5 MB
    A.4.1Sponsor's protocol code numberPNET5MB
    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 Medical Center Hamburg-Eppendorf
    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 supportDeutsche Kinderkrebsstiftung
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationUniversity Medical Center Hamburg-Eppendorf
    B.5.2Functional name of contact pointKatja von Hoff
    B.5.3 Address:
    B.5.3.1Street AddressMartinistr. 52
    B.5.3.2Town/ cityHamburg
    B.5.3.3Post code20246
    B.5.3.4CountryGermany
    B.5.4Telephone number004940741053394
    B.5.5Fax number004940741058300
    B.5.6E-mailk.von-hoff@uke.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.2.1.2Country 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.3.4Pharmaceutical 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.3.9.4EV 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: 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.2.1.2Country 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.3.4Pharmaceutical 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 INNCARBOPLATIN
    D.3.9.1CAS number 41575-94-4
    D.3.9.4EV Substance CodeSUB06614MIG
    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: 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.2.1.2Country 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.3.4Pharmaceutical 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 INNLOMUSTINE
    D.3.9.1CAS number 13010-47-4
    D.3.9.4EV Substance CodeSUB08567MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    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.2.1.2Country 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.3.4Pharmaceutical 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 INNVINCRISTINE SULFATE
    D.3.9.1CAS number 2068-78-2
    D.3.9.4EV Substance CodeSUB05101MIG
    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 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.2.1.2Country 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.3.4Pharmaceutical 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.3.9.1CAS number 6055-19-2
    D.3.9.3Other descriptive nameCYCLOPHOSPHAMIDE MONOHYDRATE
    D.3.9.4EV Substance CodeSUB16414MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number106.9
    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
    Children with medulloblastoma of standard risk. Medulloblastoma is a highly cellular malignant embryonal neoplasm classified as a Primitive Neuro-ectodermal Tumour [PNET]
    bambini di età superiore a 3 anni affetti da medulloblastoma a rischio basso o intermendio
    E.1.1.1Medical condition in easily understood language
    Medulloblastoma is a type of brain tumour that mainly affects children
    Il medulloblastoma è un tumore cerebrale che si presenta principalmente nei bembini
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.1
    E.1.2Level PT
    E.1.2Classification code 10027107
    E.1.2Term Medulloblastoma
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Treatment Arm- LR
    - to confirm that the 3-year Event-Free Survival rate in children and adolescents with standard-risk medulloblastoma having a low-risk biological profile remains in excess of 80% when patients are treated with 23.4 Gy neuraxis irradiation plus boost to the primary tumor, and reduced-intensity chemotherapy
    Treatment Arm - SR
    - to test whether the Event-Free Survival in children and adolescents with standard-risk medulloblastoma having an average-risk biological profile is different for patients treated with or without carboplatin concomitantly with radiotherapy (23.4 Gy neuraxis irradiation plus boost to the primary tumor) followed by a modified maintenance chemotherapy.
    Pazienti a basso rischio. Dimostrare, nel gruppo di pazienti a basso rischio biologico, un tasso di soprevvivenza libera da malattia (EFS), a 3 anni, superiore all'80% nonostante una chemioterapia di mantenimento di intensitò ridotta rispetto al passato; pazienti a rischio intermendio: sarà di verificare se la sopravvivenza liberada eventi nei bambini e negli adolescenti affetti da medulloblastoma a rischio standard con profilo biologico di rischio maggiore cambia a seconda che i pazienti vengano trattati con o senza la somministrazione di carboplatino concomitante alla radioterapia, seguita da un regime modificati di chemioterapia di mantenimento.
    E.2.2Secondary objectives of the trial
    Treatment Arm - LR
    - Overall Survival rate, and pattern of relapse
    - late effects of the reduced-dose approach
    - to conduct comprehensive studies in a prospective fashion on the biological basis of WNT-subgroup medulloblastoma, with the aim of identification, investigation and validation of biomarkers and drug targets with therapeutic potential in this disease subgroup.
    Treatment Arm - SR
    - Overall Survival Rate, Progression-free survival rates, and pattern of relapse
    - to test the feasibility of carboplatin treatment concomitantly with radiotherapy
    - late effects in the randomized treatment arms
    - to conduct comprehensive studies in a prospective fashion on the biological basis of standard-risk medulloblastoma with the aim of identification, investigation and validation of biomarkers and drug targets with therapeutic potential in this disease subgroup.
    pazienti a basso rischio: valutazione del tasso di sopravvivenza globale, degli effetti a lungo termine del trattamento e della qualità di vita dei pazienti; pazienti a rischio intermedio: valutazione degli effetti a lungo termine del trattamento e della qualità di vita dei pazienti;
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Substudies will only be conducted in Germany.
    Sottostudi saranno effettuati esclusivamente in Germania
    E.3Principal inclusion criteria
    a) Age at diagnosis, at least 3 - 5 years (depending on the country) and less than 22 years.
    The date of diagnosis is the date on which first surgery/biopsy is undertaken.

    b) Histologically proven medulloblastoma, including the following subtypes, as defined in the WHO classification (2007):
    classic medulloblastoma desmoplastic/nodular medulloblastoma Pre-treatment central pathology review is considered mandatory.

    c) Standard risk medulloblastoma, defined as:
    - total or near total surgical resection with less than or equal to 1.5 cm2 (measured on axial plane) of residual
    tumour on early postoperative MRI, without and with contrast, on central review;
    - no CNS metastasis on MRI (cranial and spinal) on central review; )
    - no tumour cells on the cytospin samples of lumbar CSF (see chapter 8.1.2. Post-operative Period, page 4,),
    according to national regulations a CSF review might me required.
    - no clinical evidence of extra-CNS metastasis.

    In patients with significant residual tumor (> 1.5 cm2) after first surgery, secondary surgery should be considered. Patients whith a reduction of postoperative residual tumor through second surgery to less than or equal to 1.5 cm2 are eligible, if second surgery is performed within 14 days after first surgery.

    d) Submission of high quality biological material including fresh frozen tumor samples for the molecular assessment of biological markers (such as the assessment of MYC gene copy number status) in national biological reference centers.

    e) No amplification of MYC or MYCN (determined by FISH).

    f)
    Treatment Arm - LR, low-risk biological profile, defined as ß-catenin nuclear immuno-positivity by IHC (mandatory) and / or mutation analysis (optional).For PNET 5 MB - SR, average-risk biological profile, defined as ß-catenin nuclear immuno-negativity by IHC (mandatory) and mutation analysis (optional)
    Treatment Arm- SR, average-risk biological profile, defined as ß-catenin nuclear immuno-negativity by IHC (mandatory) and mutation analysis (optional) .

    g) No prior therapy for medulloblastoma other than surgery.

    h) Radiotherapy aiming to start no more than 28 days after surgery. Failure to start radiotherapy within 40 days after surgery renders patients ineligible for the study.

    i) CTC grades < 2 for liver, renal, and haematological function.

    j) no significant sensineural hearing deficit as defined by pure tone audiomentry with bone conduction or air conduction and normal tympanogram shows no impairement ≥ 20 dB at 1-3 kHz. If performance of pure tone audiometry is not possible postoperatively, normal otoacoustic emissions are acceptable, if there is no history of hearing deficit.

    k) No medical contraindication to radiotherapy or chemotherapy, such as preexisting DNA breakage syndromes (e.g. Fanconi Anemia, Njimwegen breakage syndrome) Gorlin Syndrome or other reasons as defined by patient’s clinician;

    l) No identified Turcot and Li Fraumeni syndrome.

    m) Written informed consent (and patient assent where appropriate) for therapy according to the laws of each participating country.

    n) National and local ethical committee approval according to the laws of each participating country (to include approval for biological studies).
    età compresa tra 3 e 22 anni, diagnosi istologica di medulloblastoma, classificazione in base al profilo di beta-catenina in pazienti a basso rischio e a rischio intermedio, invio di materiale fresco per le valutazioni molecolari dei marcatori biologici, assenza di sindromi di Turcot e Li Fraumeni, nessuna terapia precedente (eccetto la chirurgia) per il medulloblastoma, firma del consenso informato.
    E.4Principal exclusion criteria
    a) One of the inclusion criteria is lacking.
    b) Brainstem or supratentorial primitive neuro-ectodermal tumour.
    c) Atypical teratoid rhabdoid tumour.
    d) Medulloepithelioma.
    e) Large-cell medulloblastoma, anaplastic medulloblastoma, or medulloblastoma with extensive nodularity (MBEN), centrally confirmed.
    f) Unfavourable or undeterminable biological profile, defined as amplification of MYC or MYCN, or not determinable MYC or MYCN or ß-catenin.
    g) Metastatic medulloblastoma (on CNS MRI and/or positive cytospin of postoperative lumbar CSF).
    h) Patient previously treated for a brain tumour or any type of malignant disease.
    i) DNA breakage syndromes (e.g. Fanconi anemia, Nijmegen breakage syndrome) or other, or identified Gorlin, Turcot, or Li Fraumeni syndrome.
    j) Patients who are pregnant.
    k) Female patients who are sexually active and not taking reliable contraception.
    l) Patients who cannot be regularly followed up due to psychological, social, familial or geographic reasons.
    m) Patients in whom non-compliance with toxicity management guidelines can be expected.
    diagnosi diversa da medulloblastoma (variante classica, desmoplastica, nodulare), profili biologici sfavorevoli definiti come l’amplificazione di MYC o MYCN o stato non determinabile di MYC, MYCN o beta-catenina, malattia metastatica, precedenti trattamenti per tumore cerebrale o altro tumore, sindromi genetiche, pazienti femmine in gravidanza.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is event-free survival (EFSOP) for the treatment arm SR and 3-years EFS rate for the treatment arm LR
    prima progressione di malattia, prima recidiva, diagnosi di secondo tumore, morte.
    E.5.1.1Timepoint(s) of evaluation of this end point
    not applicable
    non applicabile
    E.5.2Secondary end point(s)
    1) Event-free survival (EFSend)
    2) Overall survival (OSOP)
    3) Overall survival (OSend)
    4) Progression-free survival (PFSOP)
    5) Feasibility of carboplatin treatment
    6) Residual tumor (<1.5 cm2) will be estimated by central MRI review postoperatively
    7) Relapse pattern will be evaluated at the end of therapy
    8) Indirect measures for quality of survival
    9) Ototoxicites
    10) Endocrine function
    11) Neurologic function
    12) Biological tumour markers
    13) Leukoencephalopathy (LEP)
    14) Audit of compliance with protocol defined therapy
    sopravvivenza libera da eventi, sopravvivenza globale (dal primo intervento e dal termine della chemioterapia), sopravvivenza libera da progressione, fattibilità del trattamento con carboplatino concomitante alla radioterapia, misure indirette della valutazione della qualità della vita, ototossicità, valutazione della funzione endocrina, funzioni neurologiche.
    E.5.2.1Timepoint(s) of evaluation of this end point
    not applicable
    non applicabile
    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 No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    valutazione sequele a lungo termine e qualità della vita
    valutazione sequele a lungo termine e qualità della vita
    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) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other 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 concerned13
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA15
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years9
    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: 360
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 216
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 108
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 36
    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 Yes
    F.3.3.2Women of child-bearing potential using contraception No
    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
    For children and adolescents who are too young to give informed consent, depending on national definitions, informed consent will be obtained in written form from the parents. Patient assent may also be obtained, depending on national requirements.
    a soggetti che sono troppo piccoli per dare il proprio consenso,in base alla legisl. locale,verrà richiesta la sottoscrizione di un C.I.da parte dei genitori/tutori.L’assenso dei pazienti può essere richiesto o meno in funzione della legisl.loc
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state90
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 360
    F.4.2.2In the whole clinical trial 360
    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 SIOP International Society of Peadiatric Onology
    G.4.3.4Network Country Switzerland
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-01-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-12-17
    P. End of Trial
    P.End of Trial StatusOngoing
    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