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    Summary
    EudraCT Number:2018-003355-38
    Sponsor's Protocol Code Number:D0816C00025
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2019-11-06
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2018-003355-38
    A.3Full title of the trial
    A Phase I, Open-label, Parallel Group Study to Investigate Olaparib Safety and Tolerability, Efficacy and Pharmacokinetics in Paediatric Patients with Solid Tumours
    Estudio de fase I, abierto, de grupos paralelos para investigar la seguridad, la tolerabilidad, la eficacia y la farmacocinética de olaparib en pacientes pediátricos con tumores sólidos
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to find out whether olaparib is safe and well tolerated when administered to children and adolescents.
    Estudio para identificar si olaparib es seguro y bien tolerado administrado en niños y adolescentes.
    A.3.2Name or abbreviated title of the trial where available
    Olaparib monotherapy in paediatric patients
    Olaparib en monoterapia en pacientes
    A.4.1Sponsor's protocol code numberD0816C00025
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/262/2018
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    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 supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca AB
    B.5.2Functional name of contact pointClinical Trial Transparency
    B.5.3 Address:
    B.5.3.1Street AddressForskargatan 18
    B.5.3.2Town/ citySödertälje
    B.5.3.3Post code151 85
    B.5.3.4CountrySweden
    B.5.6E-mailClinicalTrialTransparency@astrazeneca.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 nameOlaparib 25 mg
    D.3.2Product code AZD2281
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOlaparib
    D.3.9.1CAS number 763113-22-0
    D.3.9.2Current sponsor codeAZD2281
    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 Yes
    D.2.1.1.1Trade name LYNPARZA®
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca AB
    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 nameOlaparib 100 mg
    D.3.2Product code AZD2281
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOlaparib
    D.3.9.1CAS number 763113-22-0
    D.3.9.2Current sponsor codeAZD2281
    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 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
    Solid Tumours
    Tumores sólidos
    E.1.1.1Medical condition in easily understood language
    Malignant cancer
    Cáncer maligno
    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
    To describe the safety and tolerability of olaparib monotherapy and identify the RP2D of olaparib in the paediatric population.
    Describir la seguridad y tolerabilidad de olaparib en monoterapia e identificar la DRF2 de olaparib en la población pediátrica.
    E.2.2Secondary objectives of the trial
    - To describe the paediatric PK profile and to identify the adult equivalent (300 mg bd tablet) dose based upon PK modelling.
    - To determine target engagement in paediatric patients via measurement of PARP inhibition in PBMCs.
    - To describe anti-tumour activity based upon RECIST v1.1 criteria or INRC in paediatric patients with measurable or non-measurable assessable disease including in the subset of the minimum of 10 patients with deleterious or suspected deleterious HRR mutations.
    - Describir el perfil de FC pediátrica e identificar la dosis equivalente en adultos (comprimido de 300 mg 2 v/d) a partir del modelo de FC.
    - Determinar la fijación selectiva en pacientes pediátricos mediante la medición de la inhibición de PARP en CMSP.
    - Describir la actividad antitumoral basada en los criterios RECIST v1.1 o INRC en pacientes pediátricos con enfermedad evaluable medible o no medible, incluido en el subgrupo de un mínimo de 10 pacientes con mutaciones de RRH nocivas o supuestamente nocivas.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1 Paediatric patients with pathologically confirmed relapsed or refractory non-CNS solid tumours (excluding lymphoid malignancies), with a HRR deficiency, and for whom there are no standard treatment options. Eligible patients may include but not be limited to those with osteosarcoma, rhabdomyosarcoma, non-rhabdomyosarcoma soft tissue sarcoma, Ewing Sarcoma and neuroblastoma.
    (a) Any number of prior treatment regimens allowed.
    (b) A select group of first-line patients may be considered on a case by case basis to be eligible for screening and enrolment. These patients will be enrolled based on Investigator assessment after discussion with the sponsor as patients for whom no curative standard of care treatment options exist or such therapies are not tolerable.
    2. An FFPE tumour sample from the primary cancer (all patients) and blood sample (patients ≥2 years old) suitable for central HRR testing must be provided for each patient. The blood and tumour samples will be collected for central assessment of HRR status using a central laboratory. Patients with a known HRR deficiency (based on local testing) are not required to wait for the results of the central test to proceed with the main part of the study, assuming all other eligibility criteria are met. The blood (from patients with a known HRR deficiency) and tumour samples for central confirmation should be shipped to the central laboratory following enrolment; patients with unknown HRR deficiency status will have their blood samples sent for central confirmation prior to enrolment.
    (a) A FFPE tumour tissue block is required, but if not available, tissue sections are accepted. The tumour specimen submitted should be of sufficient quantity to allow for HRR mutation status and other exploratory biomarker analyses.
    (b) Patients who don’t have an archival tumour sample may be allowed to provide a newly biopsied FFPE tumour tissue sample provided the sample is taken as part of routine clinical practice. The most recent sample available should be provided. Tumour lesions used for newly acquired biopsies should not be the same lesions used as RECIST v1.1 or INRC target lesions, unless there are no other lesions suitable for biopsy (re-assessment after biopsy may be required).
    3. Lansky scale ≥50 for patients ≤16 years of age; or Karnofsky score ≥50 for patients >16 years of age (see Appendix F).
    4. For all non-neuroblastoma tumours, patients must have at least 1 lesion (measurable and/or non-measurable), not previously irradiated, that can be accurately assessed at baseline and is suitable for repeated assessment using RECIST v1.1. Lesions in a previously irradiated field can be used as measurable disease, provided that there has been demonstrated progression in the lesion and the lesion measures at least 20 mm.
    5. For neuroblastoma tumours, patients must have:
    (a) Radiographical assessable disease with at least 1 lesion (measurable and/or non-measurable) that can be accurately assessed at baseline and is suitable for repeated assessment using International Neuroblastoma Response Criteria (INRC); OR,
    (b) Disease evidenced by uptake of meta-iodobenzylguanidine- (MIBG) or fluorodeoxyglucose positron emission tomography (FDG-PET) scans.
    6. Patients must have normal organ and bone marrow function measured within 28 days prior to administration of study treatment as defined in the protocol.

    Please refer to the protocol for full inclusion criteria.
    1. Pacientes pediátricos con tumores sólidos que no afecten al SNC, en recaída o resistentes al tratamiento y confirmados mediante pruebas anatomopatológicas (excluidas las neoplasias malignas linfoides), con deficiencia de la HRR, y para los cuales no existen opciones terapéuticas de referencia. Los pacientes idóneos pueden incluir, entre otros, los que presentan osteosarcoma, rabdomiosarcoma, sarcoma de partes blandas que no sea rabdomiosarcoma, sarcoma de Ewing y neuroblastoma.
    (a) Está permitido cualquier número de tratamientos previos.
    (b) Se podrá considerar para su selección e inclusión a un grupo determinado de pacientes que estén en tratamiento de primera línea, analizando caso por caso. Estos pacientes se inscribirán a partir de la evaluación del investigador después de analizarlo con el promotor en el caso de los pacientes para los que no existan opciones terapéuticas de referencia que sean curativas o que no toleren dichos tratamientos.
    2. Para cada paciente debe proporcionarse una muestra tumoral FFIP del cáncer primario (todos los pacientes) y una muestra de sangre (pacientes de ≥ 2 años) que sean apropiadas para la realización de pruebas centralizadas de la HRR. Las muestras de sangre y tumor se obtendrán para la evaluación centralizada del estado respecto de la HRR en un laboratorio central. En el caso de los pacientes con una deficiencia conocida de la HRR (según un análisis local) no es necesario esperar los resultados de la prueba centralizada para proceder con la parte principal del estudio, suponiendo que se cumplen todos los demás criterios de elegibilidad. Las muestras de sangre (procedentes de los pacientes con deficiencia conocida de la HRR) y de tumor para la confirmación centralizada se deben enviar al laboratorio central después de la inscripción; las muestras de sangre de los pacientes con estado desconocido respecto de la deficiencia de la HRR se enviarán para confirmación centralizada antes de la inscripción.
    (a) Se requiere un bloque de tejido tumoral FFIP pero, si no está disponible, se aceptan cortes de tejido. La muestra tumoral enviada debería ser de una cantidad suficiente como para poder determinar el estado mutacional de la HRR y otros análisis de biomarcadores exploratorios.
    (b) En el caso de los pacientes de quienes no exista una muestra tumoral de archivo, se podrá utilizar una muestra de tejido tumoral FFIP de una biopsia reciente, siempre que la muestra se haya obtenido como parte de la práctica clínica habitual. Se debe proporcionar la muestra más reciente disponible. Las lesiones tumorales que se elijan para las biopsias de obtención reciente no deben ser las mismas lesiones que se emplearon como lesiones indicadoras para la evaluación según los criterios RECIST v1.1 o INRC, a menos que no existan otras lesiones apropiadas para la biopsia (puede ser necesaria una revaluación después de la biopsia).
    3. Escala de Lansky ≥ 50 para los pacientes ≤ 16 años; o puntuación de Karnofsky ≥ 50 para los pacientes > 16 años (véase Apéndice F).
    4. En relación con todos los tumores que no son neuroblastomas, los pacientes deben presentar al menos 1 lesión (mensurable y/o no mensurable), no tratada previamente con radioterapia, que se pueda evaluar de forma precisa en el inicio y que sea adecuada para repetir la evaluación mediante los criterios RECIST v1.1. Las lesiones localizadas en un campo irradiado previamente pueden usarse como enfermedad mensurable, siempre y cuando se haya demostrado progresión de la lesión y esta mida 20 mm como mínimo.
    5. En el caso de los tumores que son neuroblastomas, los pacientes deben tener:
    (a) enfermedad evaluable radiológicamente, con al menos 1 lesión (mensurable y/o no mensurable), que pueda evaluarse con precisión en el inicio y sea adecuada para evaluaciones repetidas mediante los criterios internacionales de respuesta del neuroblastoma (International Neuroblastoma Response Criteria, INRC); O,
    (b) enfermedad demostrada mediante tomografía por emisión de positrones (PET) con metayodobencilguanidina (MIBG) o fluorodesoxiglucosa (FDG).
    6. Los pacientes deben tener una función orgánica y medular normal, medida en los 28 días anteriores a la administración del tratamiento del estudio, como se define en el protocolo.

    Por favor, consulte el protocolo para obtener la lista completa de criterios de inclusión.
    E.4Principal exclusion criteria
    1. Patients with MDS/AML or with features suggestive of MDS/AML.
    2. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study drug.
    3. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, lymphopenia, and the laboratory values defined in the inclusion criterion. Patients with a toxicity not reasonably expected to be exacerbated by study treatment (eg, hearing loss, gastrostomy tube) may be included after consultation with the Study Physician.
    4. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on High Resolution Computed Tomography scan, ongoing or active infection, symptomatic congestive heart failure, cardiac arrhythmia, interstitial lung disease, or any psychiatric illness or social situations that would limit compliance with study requirements, substantially increase the risk of incurring AEs from IP, or compromise the ability of the patient to give written informed assent.
    5. History of other primary malignancy unless curatively treated with no evidence of disease for ≥5 years. Non-invasive malignancies such as adequately treated non-melanoma skin cancer or in situ carcinomas that have been adequately treated may be permitted after detailed discussion with the Study Physician.
    6. Patients with CNS disease meeting the following criteria:
    (a) Symptomatic uncontrolled brain metastases at baseline. A scan to confirm the absence of brain metastases is not required. Patients with stable brain metastases are allowed as long as corticosteroids are not required for management of symptoms or progression.
    (b) Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
    7. History of active primary immunodeficiency or immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
    8. Patients with known active hepatitis (ie, Hepatitis B or C).
    (a) Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible.
    (b) Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acid.
    9 Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the Investigator (eg, unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, corrected QT interval (QTc) prolongation >500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome.
    10 Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study treatment or interpretation of patient safety or study results.

    Please refer to the protocol for full exclusion criteria.
    1. Pacientes con SMD/LMA o con signos indicativos de SMD/LMA.
    2. Pacientes que no puedan tragar medicamentos administrados por vía oral y pacientes con trastornos gastrointestinales que puedan interferir en la absorción del medicamento del estudio.
    3. Cualquier toxicidad no resuelta de grado ≥ 2 según los criterios CTCAE del NCI desde el tratamiento antineoplásico anterior, a excepción de la alopecia, el vitíligo, la linfopenia y los valores de laboratorio definidos en el criterio de inclusión. Pueden incluirse pacientes con una toxicidad que no sea razonablemente posible que empeore por el tratamiento del estudio (p. ej., hipoacusia, sonda de gastrostomía) después de consultar con el médico del estudio.
    4. Los pacientes considerados con riesgo médico alto por un trastorno médico grave no controlado, una enfermedad sistémica no maligna o a una infección activa no controlada. Los ejemplos incluyen, entre otros, arritmia ventricular no controlada, infarto de miocardio reciente (en los últimos 3 meses), trastorno convulsivo mayor no controlado, compresión medular inestable, síndrome de la vena cava superior, enfermedad pulmonar bilateral intersticial extensa según la tomografía computarizada de alta resolución, infección en curso o activa, insuficiencia cardíaca congestiva sintomática, arritmia cardíaca, enfermedad pulmonar intersticial o cualquier enfermedad psiquiátrica o situación social que, de estar presente, limitaría el cumplimiento de los requisitos del estudio, aumentaría sustancialmente el riesgo de sufrir AA por el PEI o pondría en peligro la capacidad del paciente para dar su asentimiento informado por escrito.
    5. Antecedentes de otra neoplasia maligna primaria, a menos que se haya administrado tratamiento curativo sin evidencia de enfermedad durante ≥ 5 años. Posiblemente se permita el antecedente de neoplasias malignas no infiltrantes como el cáncer de piel no melanocítico o los carcinomas in situ que se hayan tratado aceptablemente, después de analizarlo en detalle con el médico del estudio.
    6. Pacientes con enfermedad del SNC que cumplan los criterios siguientes:
    a. Metástasis cerebrales no controladas y sintomáticas en el inicio. No es necesario realizar una exploración radiológica cerebral para confirmar la ausencia de metástasis cerebrales. Los pacientes con metástasis cerebrales estables podrán participar siempre que no se precisen corticosteroides para el tratamiento de los síntomas o la progresión.
    b. Pacientes con compresión medular, a menos que se considere que han recibido tratamiento definitivo y presenten evidencia de enfermedad clínicamente estable durante 28 días.
    7. Antecedentes de inmunodeficiencia primaria activa o pacientes inmunodeprimidos, p. ej., pacientes con positividad serológica confirmada para el virus de la inmunodeficiencia humana (VIH).
    8. Pacientes con hepatitis activa conocida (es decir, hepatitis B o C).
    a. La actividad del virus de la hepatitis B (VHB) se define mediante un resultado positivo conocido del antígeno de superficie del VHB (HBsAg). Son elegibles los pacientes con una infección pasada o resuelta por el VHB (definida como la presencia de anticuerpos contra el antígeno central del virus de la hepatitis B y la ausencia de HBsAg).
    b. Los pacientes con positividad de los anticuerpos contra el virus de la hepatitis C (VHC) son elegibles solo si la prueba de reacción en cadena de la polimerasa (PCR) es negativa para el ácido ribonucleico del VHC.
    9. ECG de reposo que indica enfermedades cardíacas no controladas y potencialmente reversibles, a criterio del investigador (p. ej., isquemia inestable, arritmia sintomática no controlada, insuficiencia cardíaca congestiva, prolongación del intervalo QT corregido [QTc] > 500 ms, trastornos electrolíticos, etc.), o pacientes con síndrome de QT largo congénito.
    10. Cualquier trastorno que, en opinión del investigador, pueda interferir en la evaluación del tratamiento del estudio o en la interpretación de la seguridad del paciente o de los resultados del estudio.
    E.5 End points
    E.5.1Primary end point(s)
    DLTs, RP2D, AEs/SAEs/deaths, discontinuation rate of olaparib treatment due to AEs throughout the study, clinical chemistry/haematology parameters, vital signs.
    TLD, DRF2, AA/AAG/muertes, tasa de interrupción del tratamiento con olaparib debido a AA a lo largo del estudio, parámetros de bioquímica clínica/hematología, constantes vitales
    E.5.1.1Timepoint(s) of evaluation of this end point
    Please refer to the Schedule of Assessments of the protocol.
    Por favor, consulte el calendario de evaluaciones del protocolo.
    E.5.2Secondary end point(s)
    - PK parameters: CLss/F, Css,max, Css, min, tss,max, AUCss, dose normalised AUCss, AUC(0-8), AUC0-t, and dose normalised Css,max
    - Mean % inhibition of PARP-1 from baseline in PBMC samples
    - ORR, DCR and DoR as defined by Investigator-assessed RECIST v1.1 or INRC
    - Parámetros de FC: CLee/F, Cee,máx., Cee,mín., tee,máx., AUCee, AUCee, AUC(0-8), AUC0-t normalizada por la dosis y
    Cee,máx.normalizada por la dosis
    - % de inhibición media de PARP-1 respecto al inicio en
    muestras de CMSP
    - TRO, TCE y DdR según los criterios RECIST v1.1 o INRC evaluados por el investigador.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Please refer to the Schedule of Assessments of the protocol.
    Por favor, consulte el calendario de evaluaciones del protocolo.
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other Yes
    E.7.1.3.1Other trial type description
    Determination of the recommended Phase II dose (RP2D) in paediatric patients
    Determinación de la dosis recomendada de Fase II (DRF2) en pacientes pediátricos
    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 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 Yes
    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
    Diferentes dosis de olaparib
    Different dose of olaparib
    E.8.2.4Number of treatment arms in the trial15
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA 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
    Denmark
    France
    Germany
    Israel
    Korea, Republic of
    Spain
    United Kingdom
    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
    LSLV
    UPUV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months1
    E.8.9.2In all countries concerned by the trial days1
    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: 48
    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: 8
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 24
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 16
    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
    Infants and adolescents aged 6 months - 15 years will be represented by legally designated representative(s)/parent(s)
    Los bebés y adolescentes de 6 meses a 15 años de edad estarán representados por uno o varios representantes legalmente designados.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 40
    F.4.2.2In the whole clinical trial 48
    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)
    The clinical study database will close to new data at the time of the final data cut. Patients are, however, permitted to continue to receive study treatment beyond the closure of the database, if, in the opinion of the Investigator, they are continuing to receive benefit.
    La base de datos del estudio clínico se cerrará a los nuevos datos en el momento del corte de los datos finales. Sin embargo, a los pacientes se les permite continuar recibiendo el tratamiento del estudio más allá del cierre de la base de datos, si, en opinión del Investigador, continúan recibiendo beneficios.
    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 Decision2020-01-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-12-17
    P. End of Trial
    P.End of Trial StatusOngoing
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