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    Summary
    EudraCT Number:2012-003432-24
    Sponsor's Protocol Code Number:CLDK378A2201
    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:2012-10-15
    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 number2012-003432-24
    A.3Full title of the trial
    A phase II, multicenter, single-arm study of oral LDK378 in adult patients with ALK-activated non-small cell lung cancer previously treated with chemotherapy and crizotinib
    Estudio fase II, multicéntrico, con un único grupo de tratamiento, de LDK378 oral, en pacientes adultos con cáncer de pulmón de células no pequeñas con activación de ALK, tratados previamente con quimioterapia y crizotinib
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical study of oral LDK378 in adult patients with ALK-activated non-small cell lung cancer previously treated with chemotherapy and crizotinib
    Un estudio clínico de LDK398 oral en pacientes adultos con cáncer de pulmón de células no pequeñas con activación de ALK, tratados previamente con quimioterapia y crizotinib
    A.4.1Sponsor's protocol code numberCLDK378A2201
    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 Farmaceuica 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 Farmaceutica S.A.
    B.5.2Functional name of contact pointJavier Malpesa Barcones
    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+34933064464
    B.5.5Fax number+34933064290
    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.3.9.2Current 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 number25
    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.3.9.2Current 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: 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 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.3.9.2Current 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
    Non-small cell lung cancer
    Cáncer de pulmón de células no pequeñas
    E.1.1.1Medical condition in easily understood language
    Non-small cell lung cancer
    Cáncer de pulmón de células no pequeñas
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level PT
    E.1.2Classification code 10061873
    E.1.2Term Non-small cell lung cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To demonstrate the antitumor activity of LDK378, as measured by overall response rate (ORR) to LDK378 by investigator assessment
    Demostrar la actividad antitumoral de LDK378, medido con la tasa de respuesta global (TRG) a LDK378, con evaluación del investigador
    E.2.2Secondary objectives of the trial
    To evaluate response related endpoints as assessed by investigator and Blinded Independent Review Committee (BIRC):
    - Duration of response (DOR)
    - Disease control rate (DCR)
    - Time to response (TTR)
    To assess ORR by BIRC assessment
    To evaluate the safety profile of LDK378
    To evaluate progression-free survival (PFS)
    To evaluate overall survival (OS)
    Evaluar las variables relacionadas con la respuesta, evaluadas por el investigador y el Comité de Revisión Independiente Enmascarado (BIRC): duración de la respuesta (DR), tasa de control de la enfermedad (TCE), tiempo hasta la respuesta (TR); y evaluar la TRG con evaluación del BIRC.
    Evaluar el perfil de seguridad de LDK378
    Evaluar la supervivencia libre de progresión (SLP)
    Evaluar la supervivencia global (SG)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Histologically or cytologically confirmed diagnosis of locally advanced or metastatic NSCLC that carries an ALK rearrangement defined as 15% or more positive tumor cells as assessed by the FDA-approved FISH test (Abbott Molecular Inc)
    2. Age 18 years or older at the time of informed consent.
    3. Patients must have locally advanced or metastatic NSCLC that has progressed during therapy with crizotinib or within 30 days of the last dose
    4. Patients must have received 1-3 lines of cytotoxic chemotherapy (of which 1 must have been a platinum doublet) to treat their locally advanced or metastatic NSCLC
    5. Patients must have archival tissue sample available, collected either at the time of diagnosis of NSCLC or any time since.
    6. Patients must have recovered from all toxicities related to prior anticancer therapies to grade ? 2, except for patients with grade 2 nausea/vomiting and/or grade 2 diarrhea despite optimal supportive therapy who will not be allowed to participate in the study

    Other protocol defined inclusion criteria may apply
    1.Diagnóstico histológicamente o citológicamente confirmado de CPCNP metastásico o locamente avanzado portador de reordenación de ALK, definido como 15% o más de células tumorales positivas, evaluado con el test FISH aprobado por la FDA (abbot Molecular Inc)
    2.Pacientes con 18 años de edad o más en el momento del consentimiento informado
    3.Los pacientes deberán presentar CPCNP metastásico o localmente avanzado que ha progresado durante la terapia con crizotinib o dentro de los 30 días de la última dosis
    4. Los pacientes deben haber recibido 1-3 lineas de quimioterapia citotóxica (de la cual 1 debe de haber sido un doblete de platino) para tratar su CPCNP metastásico o localmente avanzado
    5. Deberá disponerse de tejido archivado, recogido en el momento del diagnóstico.
    6.Los pacientes deberán haberse recuperado de todas las toxicidades relacionadas con terapia antineoplásicas previas a grado ? 2 (CTCAE v 4.03). La excepción a este criterio es para pacientes con vómitos/náuseas de grado 2 y/o diarrea de grado 2 a pesar de terapia de soporte óptima que no podrán participar en el estudio.
    Se aplicaran otros criterios definidos en el protocolo.
    E.4Principal exclusion criteria
    1. Patients with known hypersensitivity to any of the excipients of LDK378
    2. Patients with symptomatic central nervous system (CNS) metastases who are neurologically unstable or have required increasing doses of steroids within the 2 weeks prior to study entry to manage CNS symptoms.
    3. History of carcinomatous meningitis.
    4. Presence or history of a malignant disease other than NSCLC that has been diagnosed and/or required therapy within the past 3 years.
    5. Clinically significant, uncontrolled heart disease
    6. Systemic anti-cancer therapy given after the last dose of crizotinib and prior to starting study drug.

    Other protocol defined exclusion criteria may apply
    1.Pacientes con hipersensibilidad conocida a cualquiera de los excipientes de LDK378
    2.Pacientes con metástasis del sistema nervioso central (SNC) sintomáticas que sean neurológicamente inestables o hayan precisado aumento de la dosis de esteroides dentro de las 2 semanas antes de iniciar el estudio para controlar los síntomas del SNC.
    3.Antecedentes de meningitis carcinomatosa
    4.Presencia o antecedentes de enfermedad maligna que no sea CPCNP que haya sido diagnosticado y/o precisa terapia dentro de los últimos 3 años
    5.Enfermedad cardíaca no controlada clinicamente significativa
    6.Terapia antineoplásica sistémica administrada después de la última dosis de crizotinib y antes de iniciar la medicación del estudio
    Se aplicaran otros criterios definidos en el protocolo.
    E.5 End points
    E.5.1Primary end point(s)
    ORR per RECIST v1.1 calculated as the proportion of patients with a best overall response defined as complete response or partial response (CR+PR) as assessed by investigator
    TRG según los RECIST v1.1 calculada como el porcentaje de pacientes con una mayor respuesta global definida como respuesta completa o respuesta parcial (RC + RP), evaluada por el investigador
    E.5.1.1Timepoint(s) of evaluation of this end point
    6 cycles of 28 days
    6 ciclos de 28 días
    E.5.2Secondary end point(s)
    - DOR, calculated as the time from the date of the first documented CR or PR to the first documented progression or death due to underlying cancer, by investigator and BIRC
    - DCR, calculated as the proportion of patients with best overall response of CR, PR, or SD, by investigator and BIRC
    - TTR, calculated as the time from first dose of LDK378 to first documented response (CR+PR), by investigator and BIRC
    - ORR (CR+PR) per RECIST v1.1 as assessed by BIRC
    - Adverse events and laboratory abnormalities
    - PFS, defined as time from first dose of LDK378 to progression or death due to any cause, as assessed by BIRC and investigator assessment
    - OS, defined as time from first dose of LDK378 to death due to any cause
    1. DR, calculada como el tiempo desde la fecha de la primera RC o RP documentada hasta la primera progresión documentada o muerte debido al cáncer subyacente
    2. TCE, calculada como el porcentaje de pacientes con mejor respuesta global de RC, RP o EE
    3. TR, calculada como el tiempo desde la primera dosis de LDK378 hasta la primera respuesta documentada (RC + RP)
    Y:
    4. TRG (RC+RP) según los RECIST v1.1, evaluada por el BIRC
    E.5.2.1Timepoint(s) of evaluation of this end point
    6 cycles of 28 days for all
    6 ciclos de 28 dias para todos
    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 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) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Information not present in EudraCT
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind Information not present in EudraCT
    E.8.1.4Double blind Information not present in EudraCT
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over Information not present in EudraCT
    E.8.1.7Other Information not present in EudraCT
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA24
    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
    Australia
    Belgium
    Canada
    France
    Germany
    Hong Kong
    Italy
    Korea, Republic of
    Netherlands
    Singapore
    Spain
    Sweden
    United Kingdom
    United States
    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
    The study will end once at least 75% of patients have died. Patients continuing to derive benefit from the study treatment at the end of the study in the opinion of the investigator will be able to continue receiving LDK378 on a separate protocol
    El estudio finalizará una vez que al menos el 75% de los pacientes hayan fallecido. Los pacientes que continúen beneficiandose del tratamiento al final del estudio, en la opinión del investigador, podrá continuar recibiendo LDK378 en un protocolo separado
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months8
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    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) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 6
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 2
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state8
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 54
    F.4.2.2In the whole clinical trial 137
    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)
    After discontinuing LDK378, further treatment for NSCLC is left to the physician's discretion
    Despues de ser discontinuados del LDK398, los futuros tratamientos serán elegidos a criterio del investigador.
    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 Decision2012-11-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-11-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2016-01-27
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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