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    Summary
    EudraCT Number:2016-000133-40
    Sponsor's Protocol Code Number:2016-2369
    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:2020-10-21
    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 number2016-000133-40
    A.3Full title of the trial
    European Proof-of-Concept Therapeutic Stratification Trial of Molecular Anomalies in Relapsed or Refractory Tumors - ESMART
    Studio terapeutico europeo basato sulla stratificazione delle anomalie molecolari in pazienti con tumore refrattario o recidivato.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    ESMART
    Studio terapeutico europeo basato sulla stratificazione delle anomalie molecolari in pazienti con tumore refrattario o recidivato.
    A.3.2Name or abbreviated title of the trial where available
    ESMART
    ESMART
    A.4.1Sponsor's protocol code number2016-2369
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02813135
    A.5.4Other Identifiers
    Name:NANumber:NA
    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 SponsorGUSTAVE ROUSSY
    B.1.3.4CountryFrance
    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 supportAstra Zeneca
    B.4.2CountryFrance
    B.4.1Name of organisation providing supportNovartis
    B.4.2CountryFrance
    B.4.1Name of organisation providing supportBMS
    B.4.2CountryFrance
    B.4.1Name of organisation providing supportCelgene
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGustave Roussy
    B.5.2Functional name of contact pointCRA Manager
    B.5.3 Address:
    B.5.3.1Street Address114, rue Edouard Vaillant
    B.5.3.2Town/ cityvillejuif
    B.5.3.3Post code94800
    B.5.3.4CountryFrance
    B.5.4Telephone number142115887
    B.5.5Fax number142116290
    B.5.6E-mailjonathan.rubino@gustaveroussy.fr
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRibociclib
    D.3.2Product code [LEE011]
    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 INNRibociclib
    D.3.9.1CAS number 1211441-98-3
    D.3.9.2Current sponsor codeLEE011
    D.3.9.4EV Substance CodeSUB180246
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRibociclib
    D.3.9.1CAS number 1211441-98-3
    D.3.9.2Current sponsor codeLEE011
    D.3.9.4EV Substance CodeSUB180246
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNRibociclib
    D.3.9.1CAS number 1211441-98-3
    D.3.9.2Current sponsor codeLEE011
    D.3.9.4EV Substance CodeSUB180246
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 1211441-98-3
    D.3.9.2Current sponsor codeRibociclib
    D.3.9.4EV Substance CodeSUB180246
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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.2.1.1.1Trade name POTACTASOL - 4 MG - POLVERE PER CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO - FLACONCINO(VETRO) - 4 MG(1MG/ML) 1 FLACONCINO
    D.2.1.1.2Name of the Marketing Authorisation holderACTAVIS GROUP PTC EHF
    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 nameTopotecan
    D.3.2Product code [Topotecan]
    D.3.4Pharmaceutical form Powder and solvent 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 INNTOPOTECAN
    D.3.9.1CAS number 119413-54-6
    D.3.9.2Current sponsor codeTopotecan
    D.3.10 Strength
    D.3.10.1Concentration unit mg/g milligram(s)/gram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 TEMOZOLOMIDE SUN - 5MG - CAPSULA RIGIDA - USO ORALE - BLISTER (ALU/ALU) 5X1 CAPSULE (DOSE UNITARIA)
    D.2.1.1.2Name of the Marketing Authorisation holderSUN PHARMACEUTICAL INDUSTRIES (EUROPE) B.V.
    D.2.1.2Country which granted the Marketing AuthorisationNetherlands
    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 nameTemozolomide
    D.3.2Product code [Temozolomide]
    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.3.9.2Current sponsor codeTemozolomide
    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 number5
    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.3.9.2Current sponsor codeTemozolomide
    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.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTEMOZOLOMIDE
    D.3.9.1CAS number 85662-93-1
    D.3.9.2Current sponsor codeTemozolomide
    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.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTEMOZOLOMIDE
    D.3.9.1CAS number 85622-93-1
    D.3.9.2Current sponsor codeTemozolomide
    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 number250
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 No
    D.2.1.1.1Trade name AZD1775
    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 nameAZD1775
    D.3.2Product code [AZD1775]
    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.3.9.1CAS number 1277170-60-1
    D.3.9.2Current sponsor codeAZD1775
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 1277170-60-1
    D.3.9.2Current sponsor codeAZD1775
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 CARBOPLATINO PFIZER ITALIA - 450 MG/45 ML SOLUZIONE PER INFUSIONE FLACONE 45 ML
    D.2.1.1.2Name of the Marketing Authorisation holderPFIZER ITALIA S.R.L.
    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 nameCarboplatino
    D.3.2Product code [Carboplatino]
    D.3.4Pharmaceutical form Powder and solvent 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 INNCARBOPLATINO
    D.3.9.1CAS number 41575-94-4
    D.3.9.2Current sponsor codecarboplatino
    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 number50
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCARBOPLATINO
    D.3.9.1CAS number 41575-94-4
    D.3.9.2Current sponsor codecarboplatino
    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 number150
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCARBOPLATINO
    D.3.9.1CAS number 41575-94-4
    D.3.9.2Current sponsor codecarboplatino
    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 number450
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 No
    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 nameOlaparib
    D.3.2Product code [Olaparib]
    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.3.9.1CAS number 763113-20-0
    D.3.9.2Current sponsor codeOlaparib
    D.3.9.4EV Substance CodeSUB32234
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 763113-20-0
    D.3.9.2Current sponsor codeOlaparib
    D.3.9.4EV Substance CodeSUB32234
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.1CAS number 763113-22-0
    D.3.9.2Current sponsor codeOlaparib
    D.3.9.4EV Substance CodeSUB32234
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 IRINOTECAN MYLAN GENERICS - 20 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE 1 FLACONCINO DA 5 ML
    D.2.1.1.2Name of the Marketing Authorisation holderMYLAN S.P.A.
    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 nameIrinoteca
    D.3.2Product code [Irinotecan]
    D.3.4Pharmaceutical form Powder and solvent 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 INNIRINOTECAN CLORIDRATO TRIIDRATO
    D.3.9.1CAS number 97682-44-5
    D.3.9.2Current sponsor codeIrinotecan
    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 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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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.2.5The 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 nameNivolumab
    D.3.2Product code [Nivolumab]
    D.3.4Pharmaceutical form Powder and solvent 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.3.9.2Current sponsor codeNivolumab
    D.3.9.4EV Substance CodeSUB122750
    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 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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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: 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 No
    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 nameEnasidenib
    D.3.2Product code [Enasidenib]
    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.3.9.2Current sponsor codeAG-221
    D.3.9.4EV Substance CodeSUB1899438
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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 No
    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 nameLirilumab
    D.3.2Product code [Lirilumab]
    D.3.4Pharmaceutical form Powder and solvent 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.3.9.2Current sponsor codeBMS-986015
    D.3.9.4EV Substance CodeSUB189033
    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 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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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.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 tumors in children
    Bambini, adolescenti e giovani adutli con tumori refrattari o alla ricaduta
    E.1.1.1Medical condition in easily understood language
    Relapsed or refractory tumors in children
    Bambini, adolescenti e giovani adutli con tumori refrattari o alla ricaduta
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10049280
    E.1.2Term Solid tumour
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10024329
    E.1.2Term Leukemia
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Phase I: To define or validate that the adult single agent RP2D of the selected drug or combination of drugs is safe in children/adolescents and/or that the PK profile is equivalent to that seen in adults, in pediatric/adolescent patients with malignancies which are recurrent or refractory to standard therapy.

    Phase II: To determine the preliminary activity (as measured by tumor response) of these agents in patients harboring specific molecular alterations or tumor types that may be associated with the mechanism of action of these drugs (i.e. molecularly enriched patient cohorts, where possible).
    Fase I: definire o confermare che il singolo agente alla RP2D dell’adulto del farmaco selezionato o della combinazione di farmaci selezionati sia sicuro nei bambini/adolescenti ed equivalente a quello osservato negli adulti, nei pazienti pediatrici/adolescenti con tumori maligni alla ricaduta o refrattari alla terapia standard.

    Fase II: determinare l'attività preliminare (misurata in termini di risposta tumorale) di questi agenti in pazienti che siano portatori di specifiche alterazioni molecolari o tipi di tumore che possono essere associati al meccanismo d'azione di questi farmaci (coorti di pazienti selezionati in base alle alterazioni molecolari specifiche “enriched”, ove possibile).
    E.2.2Secondary objectives of the trial
    Secondary:
    1.To characterize the toxicity profile of the agent(s) in pediatric/ adolescent patients.
    2.To characterize single or multiple-dose PK of the agent(s).
    3.To evaluate the progression free survival and incidence of long responders (>6 months).
    4.To evaluate whether the response rate is higher in the enriched population as compared to the non-enriched population overall, by targeted treatment and by arm.

    Exploratory:
    1.To explore, define and/or validate pharmacodynamic biomarkers of target inhibition, where possible.
    2.To explore relationships between measures of tumor expression of the molecular target(s), circulating tumor DNA and tumor growth.
    3. To explore the expression of immunomarker (Arm J)
    Secondari:
    1. Caratterizzare il profilo di tossicità dell'agente/i in pazienti pediatrici/adolescenti.
    2. Caratterizzare la farmacocinetica dell'agente/i.
    3. Valutare la sopravvivenza libera da progressione e l'incidenza dei responder a lungo termine (> 6 mesi).
    4. Valutare se il tasso di risposta è più alto nella popolazione arricchita rispetto alla popolazione non arricchita, mediante trattamento mirato e per braccio.
    Esplorativi:
    1. Esplorare, definire e/o validare i biomarcatori farmacodinamici (Pd) dell'inibizione del target, ove possibile.
    2. Esplorare le relazioni tra le misure dell'espressione dei bersagli molecolari nel tumore, il DNA circolante e la crescita del tumore.
    3. Esplorare l'espressione di immunomarker (braccio J)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Patients must be diagnosed with a haematologic or solid tumor malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists.
    2. Age < 18 years at inclusion; patients 18 years and older may be included after discussion with the sponsor if they have a pediatric recurrent/refractory malignancy.
    3. Patients must have had advanced molecular profiling of their recurrent or refractory tumor i.e. at the time of disease progression/relapse; exceptionally patients with advanced molecular profiling at diagnosis may be allowed.
    4. Evaluable or measurable disease as defined by standard imaging criteria for the patient’s tumor type (RECIST v1.1, RANO criteria for patients with HGG, INRC criteria for patients with NB, Leukemia criteria, etc.).
    5. Performance status: Karnofsky performance status (for patients >12 years of age) or Lansky Play score (for patients =12 years of age) = 70%.
    6. Life expectancy = 3 months
    7. Adequate organ function:
    8. Able to comply with scheduled follow-up and with management of toxicity.
    9. Females of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to initiation of treatment.
    10. For all oral medications patients must be able to comfortably swallow capsules (except for those for which an oral solution is available; nasogastric or gastrostomy feeding tube administration is allowed only if indicated).
    11. Written informed consent from parents/legal representative, patient, and age-appropriate assent before any study-specific screening procedures are conducted, according to local, regional or national guidelines.
    12. Patient affiliated to a social security regimen or beneficiary of the same according to local requirements.

    I pazienti devono avere una diagnosi di neoplasia ematologica o tumore solido in progressione nonostante la terapia standard o per il quale non esiste una terapia standard efficace.
    2. Età <18 anni al momento dell’inclusione; i pazienti di età pari o superiore a 18 anni possono essere inclusi successivamente a discussione con lo Sponsor se hanno un tumore pediatrico recidivato/ refrattario.
    3. Il tumore del paziente deve essere stato caratterizzato mediante un profilo molecolare avanzato (cioè, WES/WGS +/- RNAseq) quando è stato definito recidivo o refrattario: al momento della progressione della malattia o alla ricaduta; eccezionalmente, possono essere ammessi i pazienti con un profilo molecolare avanzato alla diagnosi.
    4. Malattia valutabile o misurabile come definita dai criteri standard di diagnostica per immagini per il tipo di tumore del paziente (RECIST v1.1, criteri RANO per i pazienti con HGG, criteri INRC per i pazienti con NB, criteri per Leucemia, ecc.).
    5. Performance status: scala di valutazione di Karnofsky (per pazienti con età >12 anni) o Lansky Play score (per pazienti con età =12 anni) con punteggio =70%. I pazienti che non sono in grado di camminare a causa di paralisi o di disabilità neurologica stabile, ma che sono su una sedia a rotelle, saranno considerati ambulanti allo scopo di valutare il punteggio di Performance status.
    6. Aspettativa di vita =3 mesi
    7. Adeguata funzionalità d’organo;
    8. In grado di aderire ai follow-up programmati e alla gestione della tossicità.
    9. Le donne in età fertile devono avere un risultato negativo del test di gravidanza su siero o urine entro le 72 ore precedenti l'inizio del trattamento. Le donne sessualmente attive in età fertile devono concordare l'utilizzo di contraccezione accettabile e appropriata durante lo studio e per almeno 6 mesi dopo l'ultima somministrazione del trattamento in studio. I pazienti maschi sessualmente attivi devono accettare di usare il preservativo durante lo studio e per almeno 6 mesi (7 mesi per il braccio J) dopo l'ultima somministrazione del trattamento in studio. La contraccezione accettabile è specificata nell'appendice 12.
    10. Per tutti i farmaci orali i pazienti devono essere in grado di deglutire le capsule (ad eccezione di quelli per i quali è disponibile una soluzione orale); la somministrazione tramite sondino nasogastrico o gastrostomia è consentita solo se clinicamente indicata.
    11. Consenso informato scritto dei genitori/rappresentanti legali (o del paziente ed eventuale assenso in base all'età) prima che sia condotta qualsiasi procedura studio-specifica di screening, secondo le linee guida locali, regionali o nazionali.
    12. Paziente che abbia la copertura del Sistema Sanitario Nazionale.
    E.4Principal exclusion criteria
    1. Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of corticosteroids or local CNS-directed therapy to control their CNS disease. Patients on stable doses of corticosteroids for at least 7 days prior to receiving study drug may be included.
    2. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter drug absorption of oral drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome).
    3. Clinically significant, uncontrolled heart disease (including history of any cardiac arrhythmias, e.g., ventricular, supraventricular, nodal arrhythmias, or conduction abnormality, unstable ischemia, congestive heart failure within 12 months of screening)
    4. Active viral hepatitis or known human immunodeficiency virus (HIV) infection or any other uncontrolled infection.
    5. Presence of any = CTCAE grade 2 treatment-related toxicity with the exception of alopecia, ototoxicity and peripheral neuropathy.
    6. Systemic anticancer therapy within 21 days of the first study dose or 5 times its half-life, whichever is less.
    7. Previous myeloablative therapy with autologous hematopoietic stem cell rescue within 8 weeks of the first study dose
    8. Allogeneic stem cell transplant within 3 months prior to the first dose. Patients receiving any agent to treat or prevent graft-versus-host disease (GVHD) post bone marrow transplant are not eligible for this trial.
    9. Radiotherapy (non-palliative) within 21 days prior to the first dose of drug (or within 6 weeks for therapeutic doses of MIBG or craniospinal irradiation).
    10. Major surgery within 21 days of the first dose. Gastrostomy, ventriculo-peritoneal shunt, endoscopic ventriculostomy, tumor biopsy and insertion of central venous access devices are not considered major surgery, but for these procedures, a 48 hour interval must be maintained before the first dose of the investigational drug is administered.
    11. Currently taking medications with a known risk of prolonging the QT interval or inducing Torsades de Pointes (Refer to Appendix 8).
    12. Currently taking medications that are mainly metabolized by CYP3A4/5, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or the drug transporters Pgp (MDR1), BCRP, OATP1B1, OATP1B3, OCT1 and OCT2 and have a low therapeutic index that cannot be discontinued at least 7 days or 5 x reported elimination half-life prior to start of treatment with any of the investigational drugs and for the duration of the study (Refer to Appendix 9).
    13. Known hypersensitivity to any study drug or component of the formulation.
    14. Pregnant or nursing (lactating) females.
    15. Vaccinated with live, attenuated vaccines within 4 weeks of the first dose of study drug.
    1. Pazienti con metastasi sintomatiche del sistema nervoso centrale (CNS) che sono neurologicamente instabili o che richiedono dosi crescenti di corticosteroidi o terapia locale sul Sistema Nervoso Centrale (SNC) per controllare la loromalattia del SNC. Possono essere inclusi i pazienti con dosi stabili di corticosteroidi per almeno 7 giorni prima di ricevere il farmaco in studio.
    2. Compromissione della funzione gastrointestinale (GI) o malattia gastrointestinale che può alterare in modo significativo l'assorbimento dei farmaci orali (per esempio malattie ulcerose, nausea non controllata, vomito, diarrea o sindrome da malassorbimento).
    3. Cardiopatia clinicamente significativa e incontrollata (compresa storia di aritmia cardiaca, per esempio, ventricolare, sopraventricolare, aritmie nodali, o anomalia nella conduzione), ischemia instabile, insufficienza cardiaca congestizia entro 12 mesi dallo screening.
    4. Epatite virale attiva o infezione da virus dell'immunodeficienza umana (HIV) nota o qualsiasi altra infezione incontrollata.
    5. Presenza di qualsiasi tossicità correlata ai trattamenti precedenti =CTCAE di grado 2, con l'eccezione di alopecia, ototossicità o neuropatia periferica.
    6. Terapia antitumorale sistemica entro 21 giorni dalla prima dose dello studio o 5 volte la sua emivita, a seconda di quale sia il periodo minore.
    7. Precedente terapia mieloablativa con salvataggio di cellule staminali ematopoietiche autologhe entro le 8 settimane dalla prima dose del farmaco in studio
    8. Trapianto di cellule staminali allogeniche nei 3 mesi precedenti la prima dose del farmaco in studio. Non sono idonei per questo studio i pazienti che ricevono un qualsiasi agente per il trattamento o la prevenzione di malattia del trapianto contro l'ospite (GVHD, Graft-Versus Host Disease ) dopo il trapianto di midollo osseo.
    9. Radioterapia (non palliativa) entro 21 giorni prima della prima dose di farmaco (o entro le 6 settimane per dosi terapeutiche di MIBG o irradiazione craniospinale).
    10. Chirurgia maggiore entro i 21 giorni dalla prima dose. Gastrostomia, shunt ventricolo-peritoneale, ventricolostomia endoscopica, biopsia tumorale e inserimento di dispositivi di accesso venoso centrale non sono considerati interventi chirurgici maggiori, ma per queste procedure deve essere mantenuto un intervallo di 48 ore prima della somministrazione della prima dose del farmaco sperimentale.
    11. Assunzione in corso di farmaci con un rischio noto di prolungamento dell’intervallo QT o di induzione di Torsione di punta (fare riferimento all'Appendice 8).
    12. Assunzione in corso di farmaci metabolizzati principalmente da CYP3A4 / 5, CYP2C8, CYP2C9, CYP2C19, CYP2D6 o da trasportatori di farmaci Pgp (MDR1), BCRP, OATP1B1, OATP1B3, OCT1 e OCT2 e che hanno un basso indice terapeutico che non possono essere sospesi almeno 7 giorni o
    5 volte x l’emivita di eliminazione riportata, prima dell'inizio del trattamento con uno qualsiasi dei farmaci sperimentali e per la durata dello studio (fare riferimento all'Appendice 9).
    13. Ipersensibilità nota a qualsiasi farmaco in studio o componente della formulazione.
    14. Donne in gravidanza o in allattamento.
    15. Paziente vaccinato con vaccini vivi e attenuati
    E.5 End points
    E.5.1Primary end point(s)
    The recommended phase II dose (RP2D) will be defined as the adult recommended dose (adjusted for weight or BSA) if toxicity and PK profiling are similar in children and in adults, or a higher dose, providing it is below the maximum tolerated dose (MTD).
    The maximum tolerate dose (MTD) will be defined as the dose associated with or closest to 25% of DLTs in cycle 1.
    Dose Limiting Toxicities (DLT) will be defined using CTC-AE v4.03.
    La dose raccomandata per la fase 2 (RP2D) verrà definita corrispondente a quella degli adulti (aggiustata per peso o BSA – Body Surface Area) se la tossicità e il profilo di farmacocinetica risulteranno simili nella popolazione pediatrica e negli adulti, o una dose più alta di quella degli adulti se inferiore o uguale alla massima dose tollerata identificata nello studio (MTD).
    La dose massima tollerata (MTD) verrà definita come la dose associate a DLT al ciclo 1 o quella che si avvicina di più con un’approssimazione del 25%
    La Dose Limiting Toxicities (DLT) verrà definita utilizzando i CTCAE v4.03.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Cycle 1
    Ciclo 1
    E.5.2Secondary end point(s)
    Overall response rate (ORR), duration of response (DOR), progression-free survival (PFS); Adverse Events; PK parameters, including but not limited to plasma concentration time profiles, AUClast, AUCtau, Cmin, Cmax, Tmax, Clearance, Half-life time.; Relationship between the molecular profile of the tumor samples and tumor growth measured as modification of the sum of the diameters of the target lesions over time.
    Il tasso di risposta globale, overall response rate (ORR); la durata della risposta, duration of response (DoR) e la data di progressione,; Gli eventi avversi verranno descritti in accordo ai NCI CTCAE V4.03; I parametri di farmaconinetica (PK) includeranno i profili di concentrazioni plasmatiche a diversi tempi, area sotto la curva AUClast, AUCtau, Cmin, Cmax, Tmax, Clearance, tempo di dimezzamento.; Esplorare le correlazioni tra il profilo molecolare del campione tumorale, il DNA tumorale circolante e la crescita tumorale calcolata come somma dei diametri delle lesioni target nel corso del tempo.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Overall response rate (ORR), duration of response (DOR) will be defined as the time period between the first documented response (PR or CR) and the time of progression. Duration of response for patients free of progression at the cut-off date will be censored at the last Imaging response scan date; progression-free survival (PFS) will be defined as the time from treatment initiation until the date of first documented progression or death from any cause. Patients alive and free of progression at the cut-off date will be censored at the last assessment date.

    ; Every treatment cycle; The detection times change according to the treatment arms; Timepoint: at enrollment, at 1 week, at 2° cycle, every two cylces up to progression of desease
    ORR e DoR verranno definiti come il periodo tra la data in cui viene definita per la prima volta una risposta (parziale, PR, o completa, CR)
    PFS verrà definita secondo i criteri RECIST v1.1, RANO per i pazienti con HGG, INRC per i pazienti con neuroblastoma, etc.; Verrano rilevati durante tutti i cicli di trattamento; I tempi di rilevazione cambiano a seconda dei diversi bracci di trattamento; I prelievi verranno eseguita all'arruolamento, a distanza di 1 settimana, al 2°ciclo e ogni 2 cicli fino alla progressione di malattia
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    1/2
    1/2
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open No
    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 Yes
    E.8.1.7.1Other trial design description
    Studi di fase 1/2, basket trial multi braccio
    1/2 multi-arm basket trial
    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 trial5
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    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 Information not present in EudraCT
    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
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months126
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years0
    E.8.9.2In all countries concerned by the trial months126
    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.1.1.1In 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: 20
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 15
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 5
    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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2020-10-21. Yes
    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
    This study includes minor subjects who can only be enrolled with the consent of the subject’s legally acceptable representative.
    Lo Studio include pazienti minorenni per i quali il consenso verrà firmato dal genitore o dal legale rapprensentante
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 280
    F.4.2.2In the whole clinical trial 280
    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)
    None
    Nessuno
    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 Decision2021-02-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-05-26
    P. End of Trial
    P.End of Trial StatusOngoing
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