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    Summary
    EudraCT Number:2019-001155-39
    Sponsor's Protocol Code Number:CO40778
    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:2020-10-07
    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 number2019-001155-39
    A.3Full title of the trial
    A PHASE 1/2, OPEN-LABEL, DOSE-ESCALATION AND EXPANSION STUDY OF ENTRECTINIB (RXDX-101) IN PEDIATRICS AND YOUNG ADULTS WITH NO CURATIVE FIRST-LINE TREATMENT OPTION OR RECURRENT/REFRACTORY SOLID TUMORS AND PRIMARY CNS TUMORS
    STUDIO DI FASE 1/2, IN APERTO, DI INCREMENTO DELLA DOSE ED ESPANSIONE DI ENTRECTINIB (RXDX 101) IN PAZIENTI PEDIATRICI E GIOVANI ADULTI SENZA ALCUNA OPZIONE DI TRATTAMENTO CURATIVO DI PRIMA LINEA O CON TUMORI SOLIDI RICORRENTI/REFRATTARI E TUMORI PRIMARI DEL SNC
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Entrectinib (RXDX-101) in Pediatrics and Young Adults with No Curative First-Line Treatment Option or Recurrent/Refractory Solid Tumors and Primary CNS Tumors
    Studio di Entrectinib (RXDX-101) in pazienti pediatrici e giovani adulti senza opzione curativa di prima linea o tumori solidi ricorrenti / refrattari e tumori primari del SNC
    A.3.2Name or abbreviated title of the trial where available
    ND
    ND
    A.4.1Sponsor's protocol code numberCO40778
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/010/2019
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorF. HOFFMANN - LA ROCHE LTD.
    B.1.3.4CountrySwitzerland
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportF. Hoffman-La Roche Ltd.
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.6E-mailglobal.rochegenentechtrials@roche.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameEntrectinib
    D.3.2Product code [RO7102122]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation Yes
    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 INNENTRECTINIB
    D.3.9.1CAS number 1108743-60-7
    D.3.9.2Current sponsor codeRO7102122
    D.3.9.4EV Substance CodeSUB177830
    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: 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 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 nameEntrectinib
    D.3.2Product code [RO7102122]
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation Yes
    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 INNENTRECTINIB
    D.3.9.1CAS number 1108743-60-7
    D.3.9.2Current sponsor codeRO7102122
    D.3.9.4EV Substance CodeSUB177830
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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.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
    Solid tumors and primary central nervous system (CNS) tumors
    Tumori solidi e tumori primari del sistema nervoso centrale (SNC)
    E.1.1.1Medical condition in easily understood language
    A solid tumor is an abnormal tissue mass that arises from uncontrolled growth of cells and spreads locally or to other parts of the body and one that starts in brain is called a primary brain tumor
    Un tumore solido è una massa di tessuto anormale che deriva dalla crescita incontrollata di cellule e si diffonde altre parti del corpo e quella nel cervello è chiamata un tumore cerebrale primario
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10065147
    E.1.2Term Malignant solid tumor
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10065252
    E.1.2Term Solid tumor
    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
    •To determine the maximum tolerated dose (MTD), or recommended Phase 2 dose (RP2D), of entrectinib in pediatric patients (pediatrics and young adults) with relapsed or refractory solid tumors (Part A)
    •To evaluate efficacy of entrectinib as assessed by objective response rate (ORR) in patients with primary brain tumors harboring NTRK1/2/3 or ROS1 molecular alterations (Part B) using Response Assessment in Neuro-Oncology Criteria (RANO) and in patients with extracranial solid tumors harboring NTRK1/2/3 or ROS1 gene fusions (Part D) using Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1), as assessed by blinded independent central review (BICR)
    • Determinare la dose massima tollerata (MTD) o la dose raccomandata di Fase 2 (RP2D), di entrectinib in pazienti pediatrici (pediatrici e giovani adulti) con tumori solidi recidivanti o refrattari (Parte A)
    • Valutare l'efficacia di entrectinib come valutata dal tasso di risposta obiettiva (ORR) in pazienti con tumori cerebrali primari che presentano alterazioni molecolari NTRK1 / 2/3 o ROS1 (Parte B) usando la Valutazione di Risposta in Criteri di Neuro-Oncologia (RANO) e in pazienti con tumori extracranici solidi che ospitano fusioni di geni NTRK1 / 2/3 o ROS1 (parte D) utilizzando i criteri di valutazione della risposta in tumori solidi, versione 1.1 (RECIST v1.1), come valutato mediante revisione centrale indipendente in cieco (BICR)
    E.2.2Secondary objectives of the trial
    •To describe the safety profile of entrectinib
    •To characterize the PK of entrectinib
    •To determine the duration of response (DOR), time to response (TTR), clinical benefit rate (CBR), progression-free survival (PFS), and overall survival (OS) in all enrolled patients receiving entrectinib at the RP2D
    •To determine the intracranial tumor response, DOR, TTR, and CNS- PFS in Parts B and D patients receiving entrectinib at the RP2D and presenting with measurable primary or secondary CNS disease at baseline, using RANO or RANO-BM, as applicable
    •To describe growth, puberty, neurological and neurocognitive function of patients on treatment
    •To evaluate the efficacy of entrectinib as assessed by ORR in all patients with NTRK1/2/3 gene fusions, regardless of study phase or cohorts using RANO for CNS tumors or RECIST v1.1 for extra-cranial tumors, as assessed by BICR
    •To characterize palatability and tolerability of the age-appropriate formulation
    • Descrivere il profilo di sicurezza di entrectinib
    • Caratterizzare il PK di entrectinib
    • Determinare la DOR, il TTR, il CBR, la PFS e la OS in tutti i pazienti arruolati che ricevono entrectinib al RP2D
    • Per determinare la risposta del tumore intracranico, DOR, TTR e SNC-PFS in pazienti con parti B e D che hanno ricevuto entrectinib alla RP2D e presentando con malattia metabolica primaria o secondaria misurabile al basale, utilizzando RANO o RANO-BM, come applicabile
    • Descrivere la crescita, la pubertà, la funzione neurologica e neurocognitiva dei pazienti durante il trattamento
    • Valutare l'efficacia di entrectinib valutata dall'ORR in tutti i pazienti con fusioni di geni NTRK1 / 2/3, indipendentemente dalla fase di studio o coorti che utilizzano RANO per tumori CNS o RECIST v1.1 per tumori extra-cranici, come valutato da BICR
    • Caratterizzare l'appetibilità e la tollerabilità della formulazione appropriata per l'età
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Body surface area (BSA): Patients must have a BSA >= 0.43 m2 at the time of the study enrollment
    Disease status:
    - Phase 1 portion: Patients must have measurable or evaluable disease
    - Phase 2 portion:
    – Part B, Part D, Part C: Patients must have measurable or evaluable disease
    – Part E: Patients must have measurable or evaluable disease and will be assessed according to tumor type
    - Tumor types included below harboring NTRK1/2/3 or ROS1 gene fusions as determined locally by an appropriately validated assay performed in a Clinical Laboratory Improvement Amendments-certified or equivalently-accredited diagnostic laboratory, or centrally by a Foundation Medicine Clinical Trial Assay:
    o Phase 1 portion:
    – Part A: Relapsed or refractory extracranial solid tumors
    o Phase 2 portion:
    – Part B: Primary brain tumors with NTRK1/2/3 or ROS1 gene fusions
    – Part D: Extracranial solid tumors with NTRK1/2/3 or ROS1 gene fusions
    - Histologic/molecular diagnosis of malignancy at diagnosis or the time of relapse
    - For patients enrolled via local molecular testing, an archival tumor tissue from diagnosis or, preferably, from relapsed disease is required to be submitted for independent central testing at Foundation Medicine, Inc. laboratory
    - Age: Male or female from birth to age <= 22 years
    - Performance status: Lansky or Karnofsky score >= 60% and minimum life expectancy of at least 4 weeks
    - Prior therapy: The patient’s cancer must have no curative first-line treatment option or recurrent/refractory solid tumors and primary CNS tumors. Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to enrollment
    - Adequate bone marrow, liver, renal, cardiac and neurologic function
    - Females of childbearing potential must have a negative serum pregnancy test during screening and be neither breastfeeding nor intending to become pregnant during study participation and in the following 90 days after discontinuation of study treatment
    - Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
    - BSA: i pazienti devono avere una BSA ¿0,43 m2 al momento dell’arruolamento nello studio.
    - Stato della malattia:
    • Porzione di fase 1: i pazienti devono presentare malattia misurabile o valutabile
    • Porzione di fase 2: Parte B, D, C: i pazienti devono presentare malattia misurabile o valutabile; Parte E: i pazienti devono presentare malattia misurabile o valutabile e saranno valutati in base al tipo di tumore
    - Tipi di tumore inclusi di seguito che presentano fusioni geniche di NTRK1/2/3 o ROS1 come determinato a livello locale da un saggio convalidato eseguito in modo appropriato presso qualsiasi laboratorio diagnostico con certificazione CLIA o equivalente, oppure a livello centrale mediante un Saggio di sperimentazione clinica (CTA) di Foundation Medicine:
    • Porzione di fase 1: Parte A: tumori solidi extracranici recidivanti o refrattari
    • Porzione di fase 2:Parte B - tumori cerebrali primari con fusioni geniche di NTRK1/2/3 o ROS1; Parte D - tumori solidi extracranici (compresi NB) con fusioni geniche di NTRK1/2/3 o ROS1;
    - Diagnosi istologica/molecolare di neoplasia maligna alla diagnosi o al momento della recidiva.
    - Per i pazienti arruolati in base all’analisi molecolare locale, un tessuto tumorale d’archivio prelevato alla diagnosi o, preferibilmente, al momento della recidiva della malattia deve essere inviato per l’analisi centrale indipendente presso il laboratorio di Foundation Medicine, Inc.
    - Età: pazienti di sesso maschile o femminile di età dalla nascita <=22 anni
    - Stato prestazionale: punteggio di Karnofsky o di Lansky >=60% e aspettativa minima di vita di almeno 4 settimane
    - Terapia pregressa: per il tumore del paziente non deve essere disponibile alcuna opzione di trattamento di prima linea a scopo curativo o non devono essere presenti tumori solidi e tumori primari del SNC ricorrenti/refrattari. I pazienti devono essersi ripresi dagli effetti tossici acuti di tutte le precedenti chemioterapie, immunoterapie o radioterapie prima dell’arruolamento.
    - Funzionalità adeguata del midollo osseo, fegato, reni, cuore e sistema neurale.
    - Le donne fertili devono avere un risultato negativo al test di gravidanza sul siero effettuato durante lo screening e non devono allattare al seno né programmare una gravidanza durante la partecipazione allo studio. Le donne e gli uomini con compagne in età fertile devono accettare di evitare gravidanze durante lo studio e acconsentire all’uso di almeno 2 metodi contraccettivi efficaci (contraccettivi ormonali, metodo barriera di controllo delle nascite o astinenza) prima dell’ingresso nello studio, per tutta la durata della partecipazione allo studio e nei 90 giorni successivi all’interruzione del trattamento in studio.
    - Disponibilità e capacità di attenersi alle visite programmate, al piano di trattamento, agli esami di laboratorio e alle altre procedure dello studio
    E.4Principal exclusion criteria
    - Current participation in another therapeutic clinical trial
    - Known congenital long QT syndrome
    - Known active infections (bacterial, fungal, or viral)
    - Receiving Enzyme Inducing Antiepileptic Drugs within prior 14 days
    - All Phase 2 patients: Prior treatment with approved or investigational tyrosine receptor kinase inhibitor (TRK) or ROS1 inhibitors
    - Patients with NB with bone marrow space-only disease
    - Incomplete recovery from acute effects of any surgery prior to treatment
    - Active gastrointestinal disease or other malabsorption syndromes that would impact drug absorption
    - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or entrectinib administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for entry in to this study or could compromise protocol objectives in the opinion of the Investigator and/or Sponsor
    La conferma di uno qualsiasi dei seguenti criteri di esclusione impedirà al paziente di accedere allo studio:
    1. Attuale partecipazione ad altra sperimentazione clinica terapeutica
    2. Nota sindrome congenita da QT lungo
    3. Note infezioni attive (batteriche, fungine o virali)
    4. Assunzione di farmaci antiepilettici induttori enzimatici (EIAED) nei precedenti 14 giorni (vedere Sezione 6.1.7.2, Tabella 11)
    5. Tutti i pazienti della fase 2: precedente trattamento con inibitori di TRK o ROS1 approvati o sperimentali
    6. Pazienti affetti da NB con malattia a carico esclusivamente dello spazio midollare
    7. Recupero incompleto dagli effetti acuti di eventuali interventi chirurgici precedenti al trattamento
    8. Malattia gastrointestinale attiva (per es. malattia di Crohn, colite ulcerosa o sindrome dell’intestino corto) o altre sindromi da malassorbimento che potrebbero influire sull’assorbimento del farmaco
    9. Altra grave patologia medica o psichiatrica acuta o cronica o anomalia negli esami di laboratorio che potrebbe aumentare il rischio associato alla partecipazione allo studio o alla somministrazione di entrectinib, o che potrebbe interferire con l’interpretazione dei risultati dello studio e che, secondo il parere dello sperimentatore, renderebbe il paziente inadatto all’inclusione in questo studio o che potrebbe compromettere gli obiettivi del protocollo secondo il parere dello sperimentatore e/o dello sponsor
    E.5 End points
    E.5.1Primary end point(s)
    1. Dose limiting toxicity of entrectinib (Part A)
    2. Objective response rate (Part B)
    1. Dose limitante per la tossicologia di entrectinib (parte A)
    2. Tasso di risposta obiettiva (parte B)
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Day 1-28 of Cycle 1
    2. Up to 30 days after last dose of study drug
    1. Giorno 1-28 del ciclo 1
    2. Fino a 30 giorni dopo l'ultima dose di farmaco in studio
    E.5.2Secondary end point(s)
    1. Incidence and severity of adverse events, laboratory and electrocardiogram (ECG) abnormalities
    2. Maximal plasma concentration (Cmax) of entrectinib
    3. Time of maximal plasma concentration (Tmax) of entrectinib
    4. Area under the plasma concentration vs. time curve (AUC) of entrectinib
    5. Duration of response in patients with relapsed or refractory extracranial solid tumors
    6. Time to response in patients with relapsed or refractory extracranial solid tumors
    7. Clinical benefit rate in patients with relapsed or refractory extracranial solid tumors
    8. Progression-free survival in patients with relapsed or refractory extracranial solid tumors
    9. Intracranial tumor response in Parts B and D patients presenting with measurable primary or secondary CNS disease at baseline
    10. Duration of response in Parts B and D patients presenting with measurable primary or secondary CNS disease at baseline
    11. Time to response in Parts B and D patients presenting with measurable primary or secondary CNS disease at baseline
    12. CNS- Progression-free survival in Parts B and D patients presenting with measurable primary or secondary CNS disease at baseline
    13. Overall survival for all patients
    14. Objective response rate in all patients
    15. Acceptability and palatability assessment for capsules and age-appropriate dosage form
    1. Incidenza e gravità degli eventi avversi, anomalie di laboratorio ed elettrocardiogramma (ECG)
    2. Concentrazione plasmatica massima (Cmax) di entrectinib
    3. Tempo di concentrazione plasmatica massima (Tmax) di entrectinib
    4. Area sotto la curva concentrazione plasmatica rispetto a tempo (AUC) di entrectinib
    5. Durata della risposta in pazienti con tumori solidi extracranici recidivati ¿¿o refrattari
    6. Tempo di risposta nei pazienti con tumori solidi extracranici recidivati ¿¿o refrattari
    7. Tasso di beneficio clinico nei pazienti con tumori solidi extracranici recidivati ¿¿o refrattari
    8. Sopravvivenza libera da progressione in pazienti con tumori solidi extracranici recidivati ¿¿o refrattari
    9. Risposta del tumore intracranico nei pazienti delle parti B e D che presentano una malattia metabolica primaria o secondaria misurabile al basale
    10. Durata della risposta nei pazienti con parti B e D che presentano una malattia metabolica primaria o secondaria misurabile al basale
    11. Tempo di risposta nei pazienti delle parti B e D che presentano una malattia metastatica primaria o secondaria misurabile al basale
    12. Sopravvivenza libera da progressione del SNC nei pazienti delle parti B e D che presentano una malattia metabolica primaria o secondaria misurabile al basale
    13. Sopravvivenza globale per tutti i pazienti
    14. Tasso di risposta obiettiva in tutti i pazienti
    15. Valutazione dell'accettabilità e della palatabilità per capsule e forma di dosaggio adatta all'età
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Up to 30 days after last dose and every 3 months until death
    2-4. Cycle 1 Day 1 pre-dose and at 1, 2, 4, 6, and 24 hours post-dose; Cycle 1 Days 8, 15 and 22 pre-dose; on Cycle 2 Day 1 pre-dose and at 1, 2, 4, 6, and 24 hours post-dose; and on Day 1 of every cycle thereafter pre-dose
    5- 14. Up to 30 days after last dose of the study drug and every 3 months until death
    15. Day 1 of Cycle 1
    1. Fino a 30 giorni dopo l'ultima dose e ogni 3 mesi fino alla morte
    2-4. Ciclo 1 giorno 1 pre-dose e 1, 2, 4, 6 e 24 ore dopo la dose; Ciclo 1 giorno 8, 15 e 22 pre-dose; sulla dose iniziale di Cycle 2 Day 1 e alle 1, 2, 4, 6 e 24 ore post-dose; e al primo giorno di ogni ciclo, successivamente alla somministrazione anticipata
    5- 14. Fino a 30 giorni dopo l'ultima dose del farmaco in studio e ogni 3 mesi fino alla morte
    15. Giorno 1 del ciclo 1
    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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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
    Determine Maximum tolerated dose (MTD), or recommended Phase 2 dose (RP2D), of entrectinib in paediatric patients.
    Determinare la dose massima tollerata (MTD) o la dose raccomandata di fase 2(RP2D), di entrectinib in pazienti pediatrici.
    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
    DOSE-ESCALATION AND EXPANSION
    DOSE-ESCALATION AND EXPANSION
    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 No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Nessun altro c'è un bug nel sistema si può selezionare "Aperto" solo se è già selezionato "Controlla
    No one else there is a bug in the system you can select "Open" only if is already selected "Checked"
    E.8.2.4Number of treatment arms in the trial1
    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 EEA12
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    France
    Germany
    Italy
    Spain
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    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 years11
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years11
    E.8.9.2In all countries concerned by the trial months1
    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: 25
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 25
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 18
    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 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
    Young children under the age of 18.
    Bambini sotto i 18 anni.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state5
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 14
    F.4.2.2In the whole clinical trial 68
    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 Decision2020-01-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-09-25
    P. End of Trial
    P.End of Trial StatusOngoing
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