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    The EU Clinical Trials Register currently displays   39363   clinical trials with a EudraCT protocol, of which   6448   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2012-002074-31
    Sponsor's Protocol Code Number:CLDK378X2103
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2013-06-10
    Trial results View 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 ConcernedSpain - AEMPS
    A.2EudraCT number2012-002074-31
    A.3Full title of the trial
    A Phase I, open-label, dose escalation study of LDK378 in pediatric patients with malignancies that have a genetic alteration in anaplastic lymphoma kinase (ALK)
    Estudio fase I, abierto, de escalado de dosis de LDK378 en pacientes pediátricos con enfermedades malignas que presentan una alteración genética en la quinasa del linfoma anaplásico (ALK)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of safety and efficacy in pediatric patients with ALK-activated tumors
    Estudio de seguridad y eficacia en pacientes pediátricos con tumores ALK-activados
    A.3.2Name or abbreviated title of the trial where available
    Phase I study of LDK378 in pediatric malignancies with a genetic alteration in ALK
    Estudio de fase I de LDK378 en tumores malignos pediátricos con una alteración genética en ALK
    A.4.1Sponsor's protocol code numberCLDK378X2103
    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 SponsorNovartis Farmacéutica, S.A.
    B.1.3.4CountrySpain
    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 supportNovartis Pharma Services AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationNovartis Farmacéutica, S.A.
    B.5.2Functional name of contact pointDepartamento Médico Oncología (GMO)
    B.5.3 Address:
    B.5.3.1Street AddressGran Via de les Corts Catalanes, 764
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08013
    B.5.3.4CountrySpain
    B.5.4Telephone number+34900353036
    B.5.5Fax number+34932479903
    B.5.6E-maileecc.novartis@novartis.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.3.2Product code LDK378
    D.3.4Pharmaceutical form Capsule
    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 INNLDK378
    D.3.9.1CAS number LDK378
    D.3.9.2Current sponsor codeLDK378
    D.3.9.3Other descriptive nameLDK378
    D.3.9.4EV Substance CodeSUB31640
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 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.3.2Product code LDK378
    D.3.4Pharmaceutical form Capsule
    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 INNLDK378
    D.3.9.1CAS number LDK378
    D.3.9.2Current sponsor codeLDK378
    D.3.9.3Other descriptive nameLDK378
    D.3.9.4EV Substance CodeSUB31640
    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 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
    malignancies characterized by genetic abnormalities in anaplastic lymphoma kinase (ALK)
    neoplasias malignas caracterizadas por anormalidades genéticas en quinasa del linfoma anaplásico (ALK)
    E.1.1.1Medical condition in easily understood language
    malignancies characterized by genetic abnormalities in anaplastic lymphoma kinase (ALK)
    neoplasias malignas caracterizadas por anormalidades genéticas en quinasa del linfoma anaplásico (ALK)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Estimate the MTD and/or RDE of LDK378 as a single agent when administered orally to pediatric patients with ALK-activated tumors
    Calcular la DMT y/o DRE de LDK378 en monoterapia, cuando se administra por vía oral a pacientes pediátricos con tumores con activación de ALK.
    E.2.2Secondary objectives of the trial
    1 -Characterize the safety and tolerability of LDK378 in the pediatric patients
    2- Characterize single and multiple-dose PK of LDK378 in pediatric patients
    3- Assess the anti-tumor activity of LDK378
    Objetivo 1: Caracterizar la seguridad y la tolerabilidad de LDK378 en pacientes pediátricos
    Objetivo 2: Caracterizar la PK de dosis múltiples y únicas de LDK378 en pacientes pediátricos
    Objetivo 3: Evaluar la actividad antitumoral de LDK378
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Diagnosed with a locally advanced or metastatic malignancy that has progressed despite standard therapy, or for which no effective standard therapy exists
    - Age ? 12 months and ? 17years
    - The tumor must carry a genetic alteration of ALK
    - Patients must have evaluable or measurable disease

    Other protocol-defined inclusion criteria may apply
    Pacientes con diagnóstico de una enfermedad maligna metastásica o localmente avanzada que hayan progresado a pesar de la terapia estándar o para los que no existe terapia estándar eficaz
    ?Edad ? 12 meses y ? 17 años
    ?El tumor deberá ser portador de una alteración genética de ALK, como una mutación, translocación o amplificación
    ?Los pacientes deberán presentar enfermedad medible o evaluable definida por uno de los siguientes criterios: RECIST v1.1 para pacientes con enfermedades malignas no hematológicas; escáner MIBG para pacientes con neuroblastoma; criterios de grupo internacional de trabajo (IWG) para pacientes con linfoma
    ?Estado funcional:
    ?Puntuación del estado funcional de Karnofsky ? 60% para pacientes >12 años de edad
    ?Puntuación de Lansky ? 50% para pacientes ? 12 años de edad
    E.4Principal exclusion criteria
    - Symptomatic central nervous system (CNS) metastases who are neurologically unstable or require increasing doses of steroids or local CNS-directed therapy (such as radiotherapy, surgery or intrathecal chemotherapy) to control their CNS disease
    - Clinically significant, uncontrolled heart disease
    - Inadequate end organ function as defined by specified laboratory values
    - Use of medications that are known to be strong inhibitors or inducers of CYP3A4/5 that cannot be discontinued at least 1 week prior to start of treatment with LDK378 and for the duration of the study
    - Use of medications that are mainly metabolized by CYP3A4/5 or CYP2C9 that cannot be discontinued at least 1 week prior to start of treatment with LDK378 and for the duration of the study.
    Other protocol-defined exclusion criteria may apply
    ?Pacientes con metástasis del sistema nervioso central (SNC) sintomáticas que sean neurológicamente inestables o precisen dosis crecientes de esteroides o terapia local dirigida al SNC (como radioterapia, cirugía o quimioterapia intratecal) para controlar su enfermedad
    ?Pacientes con enfermedad cardíaca incontrolada, clínicamente significativa o intervalo QT (QTc) corregido > 480 milisegundos, utilizando la corrección de Fridericia (QTcF)
    ?Pacientes con los siguientes valores de laboratorio durante la selección:
    ?Creatinina > 1.5 x LSN para la edad
    ?Bilirrubina total > 1.5 x LSN para la edad, excepto para pacientes con síndrome de Gilbert, que pueden ser incluidos si la bilirrubina total es ? 3.0 x LSN y la bilirrubina directa es ? 1.5 x LSN
    ?Alanina aminotransferasa (ALT) > 3 x LSN para la edad, excepto para pacientes con tumor con afectación hepática, que deberán tener un valor ? 5 x LSN
    ?Aspartato aminotransferasa sérica (AST) > 3 x LSN para la edad, excepto para pacientes con tumor con afectación hepática, que deberán tener un valor ? 5 x LSN
    ?Recuento absoluto de neutrófilos (RAN) < 0.75 x 109/L sin uso de factor de crecimiento de granulocitos durante ? 14 días
    ?Recuento de plaquetas < 50 x 109/L
    ?Hemoglobina (Hgb) < 8 g/dL
    ?Area de superficie corporal (BSA) < 0.35 m2
    ?Presencia de toxicidad ? grado 2 de los CTCAE (excepto alopecia, neuropatía periférica, ototoxicidad y linfopenia) debido a la terapia previa para el cáncer
    ?Anomalías en el potasio, magnesio, calcio o fósforo > grado 1 de los CTCAE
    ?Pacientes que reciban medicaciones que se conoce que son inhibidores o inductores potentes de CYP3A4/5 que no puedan suspenderse durante por lo menos 1 semana antes del tratamiento con LDK378 o durante todo el estudio
    ?Pacientes que reciban medicaciones que son metabolizadas principalmente por CYP3A4/5 o CYP2C9 con bajo índice terapéutico que no puedan ser suspendidas por lo menos 1 semana antes de iniciar el tratamiento con LDK378 y durante todo el estudio.
    ?Pacientes que reciban medicaciones que presentan un riesgo conocido de prolongación del intervalo QT o de inducir Torsades de Pointes
    ?Otras condiciones psiquiátricas o médicas crónicas o agudas severas o anomalías de laboratorio que puedan interferir con la interpretación de los resultados del estudio y, a criterio del investigador podrían convertir al paciente en inapropiado para el estudio
    E.5 End points
    E.5.1Primary end point(s)
    Incidence rate of Dose Limiting Toxicities (DLT)
    Tasa de incidencia de toxicidades limitantes de dosis (TLD) durante el primer ciclo de tratamiento con LDK378
    E.5.1.1Timepoint(s) of evaluation of this end point
    up to day 21 after the patient's first dose
    hasta el día 21 después de la primera dosis del paciente
    E.5.2Secondary end point(s)
    1- Number of patients with Adverse events and serious adverse events; Changes in laboratory values ; Assessments of physical examinations; Assessments of vital signs and electrocardiograms; Plasma concentration time profiles

    2- PK parameters, including AUClast, AUCtau, Cmin, Cmax, Tmax, Racc T1/2 and acc

    3- Overall response rate (ORR) and duration of response (DOR), progression-free survival (PFS) as per RECIST 1.1; Changes in disease burden in patients with lymphoma.
    1) Acontecimientos adversos y acontecimientos adversos graves, cambios en los valores de laboratorio, evaluaciones de exámenes físicos, constantes vitales y electrocardiogramas
    (2) Perfiles de tiempo-concentración plasmática, parámetros PK, incluyendo pero no limitado a AUClast, AUCtau, Cmin, Cmax, Tmax, Racc y T1/2,acc
    (3) Tasa de respuesta global (TRG) y duración de la respuesta (DR), supervivencia libre de progresión (SLP), según los RECIST 1.1 en pacientes con neuroblastoma y otros tumores sólidos y con los criterios del grupo internacional de trabajo (IWG) en pacientes con linfoma. Respuesta a MIBG en pacientes con neuroblastoma. Resolución de la enfermedad de la médula ósea en pacientes con neuroblastoma.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1- 30 months
    2- 30 months
    3- 30 months
    1 - 30 meses
    2 - 30 meses
    3 - 30 meses
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) 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 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 No
    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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA6
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    France
    Germany
    Italy
    Netherlands
    United Kingdom
    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
    Última visita del último paciente.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months5
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months5
    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: 30
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 20
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 30
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 30
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Patient age >= 12 months
    Edad de los pacientes > = 12 meses
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 36
    F.4.2.2In the whole clinical trial 80
    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)
    Expected normal treatment of that condition
    Tratamiento normal previsto para esta condición
    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 Decision2013-08-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-07-04
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2019-04-26
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