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    The EU Clinical Trials Register currently displays   43858   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2013-000256-18
    Sponsor's Protocol Code Number:CRAD001N2202
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2013-05-16
    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 number2013-000256-18
    A.3Full title of the trial
    A single-arm, open label, multi-center phase II study investigating oral everolimus tablets with dose titration in pediatric patients with relapsed or refractory Hodgkin lymphoma
    Estudio de un solo brazo, abierto, multicéntrico, fase II, de evaluación de comprimidos de everolimus con ajuste de dosis en pacientes pediátricos con linfoma de Hodgkin refractario o en recaída
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Study of efficacy and safety of everolimus in pediatric patients with Hodgkin lymphoma
    Estudio de eficacia y seguridad de everolimus en pacientes pediátricos con linfoma de Hodgkin
    A.3.2Name or abbreviated title of the trial where available
    PILLAR-3
    PILLAR-3
    A.4.1Sponsor's protocol code numberCRAD001N2202
    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 Farmcéutica 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 Yes
    D.2.1.1.1Trade name Afinitor
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameEverolimus
    D.3.2Product code RAD001
    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.3.8INN - Proposed INNeverolimus
    D.3.9.1CAS number 159351-69-6
    D.3.9.2Current sponsor codeRAD001
    D.3.9.3Other descriptive nameEVEROLIMUS
    D.3.9.4EV Substance CodeSUB02065MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    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
    relapsed or refractory Hodgkin lymphoma
    Linfoma de Hodgkin en recaída o refractario
    E.1.1.1Medical condition in easily understood language
    relapsed or refractory Hodgkin lymphoma
    Linfoma de Hodgkin en recaída o refractario
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.0
    E.1.2Level PT
    E.1.2Classification code 10020206
    E.1.2Term Hodgkin's disease
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To estimate the overall response rate (ORR), defined as the percentage of patients who achieve a CR or PR according to the revised response criteria for malignant lymphoma
    Estimar la tasa de respuesta global (TRG), definida como el porcentaje de pacientes que logran RC o RP de acuerdo con los criterios de respuesta revisados para linfoma maligno (Cheson et al 2007)
    E.2.2Secondary objectives of the trial
    1. Estimate time to response, duration of response
    2. Estimate progression-free survival (PFS)
    3. Estimate the disease control rate (DCR), defined as the percentage of patients who achieve a best overall response of CR, PR, or stable disease (SD),
    4. Estimate overall survival (OS),
    5. To evaluate pharmacokinetics
    6. Safety
    -Estimar el tiempo hasta respuesta, duración de la respuesta
    -Estimar la SLP
    -Estimar la tasa de control de la enfermedad (TCE), definida como el porcentaje de pacientes que logran una mejor respuesta global de RC, RP o enfermedad estable (EE)
    -Estimar la supervivencia global (SG)
    -Evaluar la farmacocinética
    - Seguridad
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Pediatric patients between the ages of 6 and 17 years old with classical Hodgkin lymphoma 2.Patients must meet one of the following:a.Patients eligible for ASCT must have documented progression after high-dose chemotherapy followed by autologous stem cells transplantation (ASCT), b. Patients ineligible for ASCT must be refractory to or progressed after at least two prior chemotherapy regimens; note: prior treatment with brentuximab vedotin is permitted
    3.Prior therapy with at least one gemcitabine-, vinorelbine-, or vinblastine-containing regimen
    4.Progressive HL on or within 12 months following the last treatment administration
    5.ECOG performance status ?2

    Other protocol defined inclusion criteria may apply
    ?Pacientes pediátricos entre 6 y 17 años de edad con linfoma de Hodgkin clásico
    ?Los pacientes deben cumplir una de las siguientes condiciones:
    ?Los pacientes elegibles para ASCT han de tener progresión documentada después de quimioterapia a dosis elevada seguida de autotrasplante de células madre (ASCT),
    ?Los pacientes no elegibles para ASCT han de ser resistentes o progresar después de dos o más regímenes de quimioterapia previos; nota: se permite el tratamiento previo con brentuximab vedotin
    ?Tratamiento previo con una o más pautas que contengan gemcitabina, vinorelbina o vinblastina
    ?LH progresivo en el plazo de 12 meses después de la última administración del tratamiento
    ?Estado funcional ECOG ? 2
    ?Al menos una lesión ganglionar medible con el eje largo > 20 mm o al menos una lesión extraganglionar medible (eje corto y largo ? 10 mm) de acuerdo con los criterios de respuesta revisados para linfoma maligno (Cheson et al 2007)
    ?Función de la médula ósea adecuada revelada por: ANC ?1,5 x 109/l, plaquetas ?100 x 109/l, Hb >9 g/dl;
    ?Función hepática adecuada revelada por: bilirrubina sérica total ?2,0 mg/dl, ALT y AST ?2,5x LSN (?5x LSN en pacientes con metástasis hepática), INR ?2;
    ?Función renal adecuada: creatinina sérica ?1,5x LSN;
    E.4Principal exclusion criteria
    1.Concomitant anticancer therapy (monoclonal antibody, chemotherapy, or any investigational drug); 2. Concomitant immunosuppressive agents or chronic corticosteroids use, at the time of study entry with the following exceptions: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed;
    3.Radiotherapy within four weeks prior to study entry. Patients must have recovered from radiotherapy toxicities prior to study entry;
    4. Prior therapy with mTOR inhbitors (e.g. sirolimus, temsirolimus, deforolimus);
    5. Previous treatment with an PI3K or AKT inhibitors;

    Other protocol defined exclusion criteria may apply
    ?Terapia anticancerosa concomitante (anticuerpo monoclonal, quimioterapia o cualquier fármaco de investigación)
    ?Agentes inmunosupresores concomitantes o uso crónico de corticoesteroides, en el momento de entrar en el estudio con las excepciones siguientes: se permiten aplicaciones tópicas (p. ej. exantema), aerosoles para inhalación (p. ej. enfermedad obstructiva de las vías respiratorias), colirios o inyecciones locales (p. ej. intraarticulares)
    ?Radioterapia en el plazo de cuatro semanas antes de entrar en el estudio. Los pacientes se han de haber recuperado de las toxicidades de la radioterapia antes de entrar en el estudio
    ?Diátesis hemorrágica activa o en tratamiento con medicación anti-vitamina K oral (excepto warfarina a dosis baja, heparina de bajo peso molecular y ácido acetilsalicílico o equivalente, mientras el INR sea ? 2,0)
    ?Pacientes en tratamiento con fármacos que se sabe que son inhibidores o inductores potentes de la isoenzima CYP3A (rifabutina, rifampicina, claritromicina, ketoconazol, itroconazol, voriconazol, ritinavir, telitromicina) en los últimos 5 días antes de entrar en el estudio
    ?Embolización intraarterial hepática en los últimos 6 meses. Crioablación o ablación por radiofrecuencia de metástasis hepáticas en el plazo de 2 meses de la aleatorización
    ?Tratamiento previo con inhibidores de mTOR (p. ej. sirolimus, temsirolimus, deforolimus)
    ?Tratamiento previo con inhibidores de PI3K o de AKT
    ?Alteración conocida de la función gastrointestinal (GI) o enfermedad GI que pueda alterar significativamente la absorción del everolimus por vía oral
    ?Diabetes mellitus no controlada definida por HbA1c >8% a pesar de tratamiento adecuado. Se pueden incluir pacientes con antecedente conocido de alteración de la glucosa en ayunas o diabetes mellitus (DM), pero durante todo el ensayo se deberá vigilar estrechamente la glucemia y el tratamiento antidiabético que se ajustará en la forma necesaria
    ?Pacientes con cualquiera de las afecciones médicas graves y/o no controladas siguientes:
    ?angina de pecho inestable, insuficiencia cardíaca congestiva sintomática, infarto de miocardio ?6 meses antes de la aleatorización, arritmia cardíaca grave no controlada
    ?infección grave activa o no controlada
    ?hepatopatía como cirrosis, enfermedad hepática descompensada
    ?alteración importante conocida de la función pulmonar (espirometría y DLCO 50% o inferior a lo normal y saturación de O2 ?88% en reposo en aire ambiente)
    ?diátesis hemorrágica activa
    ?Tratamiento crónico con corticoesteroides u otros agentes inmunosupresores
    ?Antecedente conocido de seropositividad al VIH
    ?Pacientes que han recibido vacunas vivas atenuadas en el plazo de 1 semana del comienzo del fármaco del estudio. El paciente también debe evitar el contacto estrecho con otras personas que hayan recibido vacunas con virus vivos atenuados: intranasal contra la gripe, sarampión, paperas, rubéola, antipolio oral, BCG, fiebre amarilla, varicela y antitifoidea TY21a
    ?Pacientes con antecedentes de otra enfermedad maligna primaria, excepto cáncer cutáneo no melanoma
    ?Pacientes con antecedentes de incumplimiento de pautas médicas, que se consideran potencialmente poco fiables o que no serán capaces de completar todo el estudio
    ?Pacientes que actualmente forman parte o que han participado en cualquier investigación clínica con un fármaco de investigación en el plazo de 1 mes antes de la administración
    ?Los varones sexualmente activos deberán utilizar preservativo durante la relación mientras tomen el fármaco del estudio y durante 30 días después de detener el tratamiento del estudio. No deben engendrar un hijo durante este período. Los varones vasectomizados también han de utilizar preservativo para evitar la liberación del fármaco a través del líquido seminal
    ?Pacientes de sexo femenino en edad fértil que no acepten la abstinencia o, si son sexualmente activas, no acepten el uso de métodos anticonceptivos altamente eficaces durante el tratamiento y durante 8 semanas después de la administración del fármaco del estudio
    ?La esterilización masculina (por lo menos 6 meses antes de la selección). Para las pacientes femeninas del estudio, el varón vasectomizado ha de ser su única pareja sexual
    ?La combinación de dos cualesquiera de los siguientes (a+b, a+c o b+c):
    ?Uso de métodos anticonceptivos hormonales orales, inyectados o implantados, u otras formas de anticoncepción hormonal que tengan una eficacia similar (tasa de fracaso <1%), por ejemplo anillo vaginal con hormonas o anticoncepción hormonal transdérmica
    ?Colocación de un dispositivo intrauterino (DIU) o sistema intrauterino (SIU)
    ?Métodos anticonceptivos de barrera: preservativo o capuchón oclusivo (diafragma o capuchón cervical) con espermicida en forma de espuma/gel/película/crema/supositorio vaginal
    E.5 End points
    E.5.1Primary end point(s)
    overall response rate (ORR)
    tasa de respuesta general (ORR)
    E.5.1.1Timepoint(s) of evaluation of this end point
    6 months after Last patient first visit
    6 meses después de la primera visita del último paciente
    E.5.2Secondary end point(s)
    1. Time to response, duration of response
    2. progression-free survival (PFS)
    3. disease control rate (DCR)
    4. overall survival (OS)
    5. Everolimus exposure in terms of pre-dose concentration (Cmin), Dose-proportionality of Cmin
    Relationship between everolimus Cmin and the responses (CR or PR vs SD, PD etc., as defined for the primary analysis)
    6. Incidence of adverse events, incidence of SAEs, change in vital signs, change in laboratory results (hematology, blood chemistry, urinalysis, coagulation, lipid profile, pregnancy tests)
    -Tiempo hasta respuesta, duración de la respuesta
    -SLP
    -TCE
    -SG
    -Exposición a everolimus en términos de concentración predosis (Cmin)
    Proporcionalidad de dosis de Cmin
    Relación entre la Cmin de everolimus y las respuestas (RC o RP frente a EE, EP, etc., definidas para el análisis principal)
    -Incidencia de acontecimientos adversos, incidencia de AAGs, cambio de constantes vitales, cambio de resultados de laboratorio (hematología, bioquímica sanguínea, análisis de orina, coagulación, perfil lipídico, pruebas de embarazo)
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. 6 months after Last patient first visit
    2. 6 months after Last patient first visit
    3. 6 months after Last patient first visit
    4. 18 months after Last patient last visit
    5. 6 months after Last patient first visit
    6. At the time of the primary analysis and upon LPLV
    1. 6 meses después de la primera visita del último paciente
    2. 6 meses después de la primera visita del último paciente
    3. 6 meses después de la primera visita del último paciente
    4. 18 meses después de la primera visita del último paciente
    5. 6 meses después de la primera visita del último paciente
    6. En el momento del análisis primario y sobre la última visita del último paciente
    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 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) 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 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.8.3 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 EEA7
    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
    Italy
    Russian Federation
    Spain
    Turkey
    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
    LPLV
    Última visita del último paciente
    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 months6
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    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) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 2
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 28
    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 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
    Childrens
    Niños
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state2
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 5
    F.4.2.2In the whole clinical trial 30
    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
    Ninguno
    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 Decision2013-07-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-06-07
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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