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    Summary
    EudraCT Number:2014-001589-85
    Sponsor's Protocol Code Number:D081FC00001
    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:2014-10-03
    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 number2014-001589-85
    A.3Full title of the trial
    A Phase III, Randomised, Double Blind, Placebo Controlled, Multicentre Study of Maintenance Olaparib Monotherapy in Patients with gBRCA Mutated Metastatic Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum Based Chemotherapy
    Estudio de Fase III, aleatorizado, en doble ciego, controlado con placebo y multicéntrico, de la monoterapia de mantenimiento con olaparib en pacientes con cáncer de páncreas metastásico con mutación de gBRCA cuya enfermedad no ha progresado con una quimioterapia de primera línea basada en el platino.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Olaparib in gBRCA Mutated Pancreatic Cancer whose Disease Has Not Progressed on First Line Platinum-Based Chemotherapy
    Olaparib en cáncer de páncreas metastásico con mutación de gBRCA cuya
    enfermedad no ha progresado con una quimioterapia de primera línea
    basada en el platino.
    A.3.2Name or abbreviated title of the trial where available
    POLO
    A.4.1Sponsor's protocol code numberD081FC00001
    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 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
    B.5.2Functional name of contact pointInformation center
    B.5.3 Address:
    B.5.3.1Street AddressNot applicable
    B.5.3.2Town/ cityNot applicable
    B.5.3.3Post codeNot applicable
    B.5.3.4CountryUnited States
    B.5.4Telephone number+34913913443
    B.5.6E-mailinformation.centre@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
    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.3.9.3Other descriptive nameOLAPARIB
    D.3.9.4EV Substance CodeSUB32234
    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.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameolaparib
    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.3.9.3Other descriptive nameOLAPARIB
    D.3.9.4EV Substance CodeSUB32234
    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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboFilm-coated tablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with gBRCA mutated metastatic pancreatic cancer whose disease has not progressed on first line platinum based chemotherapy
    Pacientes con cáncer de páncreas metastásico con mutación de gBRCA cuya
    enfermedad no ha progresado con una quimioterapia de primera línea
    basada en el platino.
    E.1.1.1Medical condition in easily understood language
    gBRCA mutated metastatic pancreatic cancer
    Cáncer de páncreas metastásico con mutación de gBRCA .
    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 determine the efficacy of Olaparib maintenance monotherapy compared to placebo by progression free survival (PFS)
    Determinar la eficacia de la monoterapia de mantenimiento con olaparib en comparación con placebo mediante la supervivencia sin progresión (SSP)
    E.2.2Secondary objectives of the trial
    ? To determine the efficacy of Olaparib maintenance monotherapy compared to placebo
    ? To assess the effect of Olaparib on the Health-related Quality of Life (HRQoL) as measured by EORTC QLQ-C30 global QoL scale.
    - Determinar la eficacia de la monoterapia de mantenimiento con olaparib en comparación con placebo.
    - Evaluar el efecto de olaparib sobre la calidad de vida relacionada con la
    salud (CdVRS), medida con la escala de CdV global EORTC QLQC30.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    For inclusion in the study patients should fulfil the following criteria:
    1. Provision of informed consent prior to any study specific procedures
    2. Patients must be male or female >o=18 years of age
    3. Histologically or cytologically confirmed pancreas adenocarcinoma receiving initial chemotherapy for metastatic disease and without evidence of disease progression on treatment
    4. Patients with measurable disease and/or non-measurable or no evidence of disease assessed at baseline by CT (or MRI where CT is contraindicated) will be entered in this study.
    5. Documented mutation in gBRCA1 or gBRCA2 that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental/lead to loss of function)
    6. Patients are on treatment with a first line platinum-based regimen for metastatic pancreas cancer, have received a minimum of 16 weeks of continuous platinum treatment and have no evidence of progression based on investigator?s opinion.
    7. Patients who have received platinum as potentially curative treatment for a prior cancer (eg ovarian cancer) or as adjuvant/neoadjuvant treatment for pancreas cancer are eligible provided at least 12 months have elapsed between the last dose of platinum-based treatment and initiation of the platinum-based chemotherapy for metastatic pancreas cancer.
    8. Patients must have normal organ and bone marrow function measured within 4 weeks prior to administration of study treatment as defined below:
    ? Haemoglobin >o= 9.0 g/dL with no blood transfusions (packed red blood cells and platelet transfusions) in the past 28 days
    ? Absolute neutrophil count (ANC) >o= 1.5 x 109/L
    ? White blood cells (WBC) >3 x 109/L
    ? No features suggestive of MDS/AML on peripheral blood smear
    ? Platelet count >o= 100 x 109/L
    ? Total bilirubin <o= 1.5 x institutional upper limit of normal
    ? AST (SGOT)/ALT (SGPT) <o= 2.5 x institutional upper limit of normal value unless liver metastases are present in which case they must be <o= 5x ULN
    ? Serum creatinine <o= 1.5 x institutional upper limit of normal (ULN)
    9. ECOG performance status 0-1 at date signing of informed consent
    10. Postmenopausal or evidence of non-childbearing status for women of childbearing potential: negative urine or serum pregnancy test. Postmenopausal is defined as:
    ? Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
    ? Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in
    the post menopausal range for women under 50
    ? Radiation-induced oophorectomy with last menses >1 year ago
    ? Chemotherapy-induced menopause with >1 year interval since last menses
    ? Surgical sterilisation (bilateral oophorectomy or hysterectomy)
    11. Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations
    12. Formalin fixed, paraffin embedded (FFPE) tumour sample from the primary tumour or a metastatic site if available or 3 unstained cytology slides if available.
    Para poder ser incluidos en el estudio los pacientes deberán cumplir los siguientes criterios:
    1. Otorgar el consentimiento informado antes de someterse a ningún procedimiento específico del estudio.
    2. Los pacientes deben ser varones o mujeres > o =18 años.
    3. Diagnóstico de adenocarcinoma de páncreas confirmado histológica o
    citológicamente, en tratamiento con quimioterapia inicial para la enfermedad metastásica y sin evidencias de progresión de la enfermedad durante el curso del tratamiento.
    4. En el estudio se incluirán pacientes con enfermedad mensurable y/o no mensurable, o sin evidencias de enfermedad según la evaluación basal mediante TAC (o RMN, en caso de estar contraindicado el TAC). Se han modificado los criterios RECIST 1.1 para permitir evaluar la progresión debida a la aparición de nuevas lesiones en los pacientes sin evidencias de la enfermedad en situación basal.
    5. Mutación documentada de gBRCA1 o gBRCA2 que se prevea o se sospeche que es nociva (es decir, se sabe o prevé que es perjudicial o que conduce a la pérdida de la función (véase la Sección 1.5).
    Pacientes que estén en tratamiento con una pauta de primera línea basada en el platino (cisplatino, carboplatino u oxaliplatino) para el cáncer de páncreas metastásico, que hayan recibido un tratamiento continuo con platino durante un mínimo de 16 semanas y que no presenten evidencias de progresión, a criterio del investigador. Los pacientes que hayan recibido una pauta con platino durante 16 semanas como mínimo pero hayan suspendido el platino debido a toxicidad, continuando con los fármacos restantes de dicha pauta, también serán elegibles si no muestran evidencias de progresión de la enfermedad dentro de las 4 semanas posteriores a la última dosis de quimioterapia.
    7. Los pacientes que hayan recibido platino como tratamiento con intención curativa de una neoplasia maligna previa (p. ej., cáncer de ovario) o como terapia adyuvante o neoadyuvante del cáncer de páncreas serán elegibles, a condición que hayan transcurrido como mínimo 12 meses entre la última administración del tratamiento basado en el platino y el inicio de la quimioterapia basada en platino para el cáncer de páncreas metastásico.
    8. Los pacientes deberán presentar una función orgánica y de la médula ósea
    normales, determinadas dentro de las 4 semanas previas a la administración del tratamiento del estudio, según se indica a continuación:
    ? Hemoglobina >o= 9,0 g/dl, sin haberse realizado transfusiones sanguíneas (de concentrados de hematíes o plaquetas) dentro de los 28 días previos
    ? Recuento absoluto de neutrófilos (RAN) >o= 1,5 x 109/l
    ? Recuento de leucocitos (LEU) >3 x 109/l
    ? Sin características sugestivas de SMD/LMA en la extensión de sangre
    periférica
    ? Cifra de plaquetas >o= 100 x 109/l
    ? Bilirrubina total <o= 1,5 x límite superior de la normalidad del centro
    ? AST (SGOT)/ALT (SGPT) <o= 2,5 x límite superior de la normalidad del centro (LSN), a menos que existan metástasis hepáticas, en cuyo caso el valor deberá ser <o= 5 x LSN
    ? Creatinina sérica <o= 1,5 x límite superior de la normalidad del centro (LSN)
    9. Estado funcional del ECOG de 0-1 en la fecha de la firma del consentimiento informado.
    Posmenopausia o, en las mujeres en edad fértil, situación de no embarazo
    demostrada: prueba de embarazo en orina o en suero negativa. La posmenopausia se define como:
    ? Amenorrea durante 1 año o más tras la suspensión de los tratamientos
    hormonales exógenos
    ? En las mujeres de menos de 50 años, niveles de las hormonas luteinizante (LH) y foliculoestimulante (FSH) en el rango de posmenopausia
    ? Ovariectomía inducida por radiación, con la última menstruación >1 año antes
    ? Menopausia inducida por quimioterapia, con un intervalo de tiempo
    transcurrido desde la última menstruación >1 año
    ? Esterilización quirúrgica (ovariectomía bilateral o histerectomía)
    11. Paciente que desee y pueda cumplir con el protocolo a lo largo de toda la duración del estudio, incluido el tratamiento y las visitas y pruebas programadas.
    12. Muestra de tumor fijada en formol e incluida en parafina (FFPE) procedente del tumor primario o de una localización metastásica (si de dispone de ella) o 3 preparaciones citológicas no teñidas (si de dispone de ellas).
    E.4Principal exclusion criteria
    Patients should not enter the study if any of the following exclusion criteria are fulfilled:
    1. Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or staff at the study site).
    2. gBRCA1 and/or gBRCA2 mutations that are considered to be non detrimental (eg, ?Variants of uncertain clinical significance? or ?Variant of unknown significance? or ?Variant, favour polymorphism? or ?benign polymorphism? etc.).
    3. Progression of tumour between start of first line platinum based chemotherapy for metastatic pancreas cancer and randomisation.
    4. Cytotoxic chemotherapy or non-hormonal targeted therapy within 28 days of Cycle 1 Day 1 is not permitted. Palliative radiotherapy must have been completed 14 or more days before Cycle 1 Day 1. The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 2 weeks prior to study treatment.
    5. Previous randomisation in the present study.
    6. Exposure to an investigational product within 30 days or 5 half lives (whichever is longer) prior to randomisation
    7. Any previous treatment with a PARP inhibitor, including Olaparib.
    8. Patients with second primary cancer, EXCEPTIONS: adequately treated nonmelanoma skin cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ (DCIS), stage 1 grade 1 endometrial carcinoma, or other solid tumours including lymphomas (without bone marrow involvement) curatively treated with no evidence of disease for >o= 5 years prior to study entry.
    9. Resting ECG with QTc > 470 msec detected on 2 or more time points within a 24 hour period or family history of long QT syndrome. If ECG demonstrates QTc >470 msec, patient will be eligible only if repeat ECG demonstrates QTc ?470 msec.
    10. Concomitant use of known potent CYP3A4/5 inhibitors such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin and nelfinavir.
    11. Persistent toxicities (?CTCAE grade 2) caused by previous cancer therapy, excluding alopecia and CTCAE grade 3 peripheral neuropathy.
    12. Patients with myelodysplastic syndrome/acute myeloid leukaemia.
    13. Major surgery within 2 weeks of starting study treatment: patients must have recovered from any effects of any major surgery.
    14. Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV).
    15. Clinically significant uncontrolled medical conditions are not permitted (eg active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris, recent (3 months) myocardial infarction, extensive bilateral interstitial lung disease, psychiatric illness that would limit ability to comply with study procedures, and any other medical condition that, in the opinion of the investigator, places the patient at unacceptable risk of toxicity. NB: Diabetes which is controlled by medication does not exclude participation in the study
    16. Patients with a history of treated CNS metastases are eligible, provided they meet all of the following criteria: Disease outside the CNS is present. No evidence of interim progression between the completion of CNS-directed therapy and the screening radiographic study. No history of intracranial haemorrhage or spinal cord haemorrhage. Minimum of 2 weeks between completion of radiotherapy and cycle 1 Day 1 and recovery from significant (Grade >o=3) acute toxicity with no ongoing
    17. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication.
    18. Pregnant or breast feeding women.
    19. Previous allogeneic bone marrow transplant.
    20. Patients with a known hypersensitivity to Olaparib or any of the excipients of the product.
    21. Whole blood transfusions in the last 120 days prior to enrolment to the study which may interfere with gBRCA testing (packed red blood cells and platelet
    Los pacientes no serán incluidos en el estudio si cumplen cualquiera de los siguientes criterios de exclusión:
    1. Participación en la planificación y/o ejecución del estudio (esto es aplicable al personal de AstraZeneca y/o del centro donde se realiza el estudio).
    2. Mutaciones de gBRCA1 y/o gBRCA2 que no se consideren perjudiciales (por ejemplo, las "variantes de trascendencia clínica incierta", "variantes de
    trascendencia desconocida", "variantes indicativas de polimorfismo" o
    "polimorfismos benignos", etc.).
    3. Progresión del tumor entre el inicio de la quimioterapia de primera línea basada en el platino para el cáncer de páncreas metastásico y la aleatorización.
    4. No está permitida la quimioterapia citotóxica ni la terapia dirigida no hormonal dentro de los 28 días previos al Día 1 del Ciclo 1. La radioterapia paliativa deberá haberse completado 14 días o más antes del Día 1 del Ciclo 1. El paciente podrá recibir una dosis estable de bisfosfonatos o denosumab para las metástasis óseas, antes y durante el estudio, siempre que dichos fármacos se hayan iniciado como mínimo 2 semanas antes de comenzar el tratamiento del estudio.
    5. Aleatorización previa en el presente estudio.
    6. Exposición a un producto en investigación dentro de los 30 días previos o de 5 semividas (lo que sea de mayor duración) inmediatamente antes de la
    aleatorización.
    7. Cualquier tratamiento previo con un inhibidor de la PARP, incluido olaparib.
    8. Pacientes con una segunda neoplasia maligna primaria. EXCEPCIONES: cáncer de piel no melanoma adecuadamente tratado, carcinoma in situ de cérvix tratado de forma curativa, carcinoma ductal in situ (CDIS), carcinoma de endometrio en estadio 1 de grado 1, u otros tumores sólidos (incluidos los linfomas sin afectación de la médula ósea) tratados de forma curativa que no hayan mostrado evidencias de enfermedad durante >o= 5 años antes de la inclusión en el estudio.
    9. ECG en reposo con un QTc > 470 ms detectado en dos o más ocasiones dentro de un período de 24 horas, o bien antecedentes familiares de síndrome de QT largo. Si el ECG muestra un QTc > 470 ms, el paciente será elegible solamente si la repetición del ECG demuestra un QTc <o= 470 ms.
    10. Uso concomitante de inhibidores potentes conocidos del CYP3A4/5, como ketoconazol, itraconazol, ritonavir, indinavir, saquinavir, telitromicina,
    claritromicina y nelfinavir. Para más detalles, véase el Apéndice H.
    11. Toxicidades persistentes (grado ?2 de CTCAE) provocadas por terapias
    antineoplásicas previas, a excepción de la alopecia y la neuropatía periférica de grado 3 de CTCAE.
    12. Pacientes con síndrome mielodisplásico/leucemia mieloide aguda.
    13. Cirugía mayor dentro de las 2 semanas previas al inicio del tratamiento del estudio: los pacientes deberán haberse recuperado de todos los efectos de cualquier intervención quirúrgica de cirugía mayor.
    14. Pacientes inmunocomprometidos; p. ej., aquellos con seropositividad conocida para el virus de la inmunodeficiencia humana (HIV).
    15. No se permiten las patologías médicas clínicamente significativas no controladas (p. ej., infecciones activas que requieren antibióticos i.v., insuficiencia cardíaca congestiva sintomática, angina de pecho inestable, infarto de miocardio reciente (dentro de los últimos 3 meses), neumopatía intersticial bilateral extensa, enfermedades psiquiátricas que limitarían la capacidad del paciente para cumplir con los procedimientos del estudio y cualquier otra patología médica que, en opinión del investigador, pueda comportar un riesgo inaceptable de toxicidad para el paciente. Nota: La diabetes controlada con medicación no excluye la participación del paciente en el estudio.
    16. Los pacientes con antecedentes de metástasis en el SNC tratadas serán elegibles, a condición de que cumplan con los siguientes criterios: Presencia de la enfermedad fuera del SNC. Sin evidencias de progresión entre la finalización de la terapia dirigida al SNC y el estudio radiológico de selección. Ausencia de antecedentes de hemorragia intracraneal o en la médula espinal. Deberán haber transcurrido un mínimo de 2 semanas entre la finalización de la radioterapia y el Día 1 del Ciclo 1.
    Recuperación de cualquier tipo de toxicidad aguda significativa (grado >o= 3), de modo que en la actualidad el paciente no requiera >o= 10 mg de prednisona al día, o una dosis equivalente de otro corticoide.
    17. Pacientes que no sean capaces de ingerir la medicación administrada por vía oral y pacientes con trastornos gastrointestinales que previsiblemente puedan alterar la absorción de la medicación del estudio.
    18.Mujeres embarazadas o en período de lactancia.
    19. Trasplante alogénico de médula ósea previo.
    20. Pacientes con hipersensibilidad conocida a olaparib o a cualquiera de los excipientes del producto.
    21. Transfusiones de sangre completa dentro de los 120 días previos a la inclusión en el estudio que puedan interferir en la prueba de gBRCA.
    E.5 End points
    E.5.1Primary end point(s)
    Determine the efficacy of Olaparib maintenance monotherapy compared to placebo by progression free survival (PFS)-Progression Free Survival (PFS) by BICR using modified RECIST 1.1
    Determinar la eficacia de la monoterapia de mantenimiento con olaparib en comparación con placebo mediante la supervivencia sin
    progresión (SSP) utilizando los criterios RECIST 1.1 modificados
    E.5.1.1Timepoint(s) of evaluation of this end point
    - Interim PFS analyses (~ 45 PFS events): PFS
    - Final PFS (~ 89 PFS events): PFS, PFS2, TDT, TFST, TSST, OS, time to deterioration of Global QoL and PAN-26 pain scale Efficacy Data
    - Final OS analyses (~ 106 OS events): PFS2, TFST, TSST, OS, time to deterioration of Global QoL and PAN-26 pain scale
    - Análisis intermedios de SSP (aprox. 45 eventos SSP): SSP
    -SSP final (aprox. 89 eventos SSP): SSP, SSP2,TST, TPTS, TSTS, SG, tiempo de deterioro de la Calidad de Vida Global y Escala de Datos de Eficacia del dolor PAN-26.
    -Análisis finales de SG (aprox. 106 eventos SG): SSP2, TPTS, SG, tiempo de deterioro de la Calidad de Vida Global y escala del dolor PAN-26.
    E.5.2Secondary end point(s)
    ? To determine the efficacy of Olaparib maintenance monotherapy compared to placebo
    ? To assess the effect of Olaparib on the Health-related Quality of Life (HRQoL) as measured by EORTC QLQ-C30 global QoL scale
    -Determinar la eficacia de la monoterapia de mantenimiento con olaparib en comparación con placebo.
    -Evaluar el efecto de olaparib sobre la calidad de vida relacionada con la salud
    (CdVRS), medida con la escala de CdV
    global EORTC QLQ-C30.
    E.5.2.1Timepoint(s) of evaluation of this end point
    - Overall Survival (observed and predicted using observed PFS and OS data), Time from randomisation to second progression (PFS2), Time from randomisation to first subsequent therapy or death (TFST), Time from randomisation to second subsequent therapy or death (TSST), Time from randomisation to study treatment discontinuation or death (TDT), Objective Response Rate by BICR using modified RECIST 1.1 criteria for evaluable patients, Disease Control Rate at 16 weeks by BICR using modified RECIST 1.1 criteria
    - Adjusted mean change from baseline in global QoL score from the EORTC-QLQC30 questionnaire
    Supervivencia Global (observada y predicha usando datos observados de SSP y SG. Tiempo desde la aleatorización hasta la segunda progresión (SSP2). Tiempo desde la aleatorización hasta la primera terapia siguiente o muerte (TPTS). Tiempo desde la aleatorización hasta la segunda terapia siguiente o muerte (TST). Objetivo de Tasa de Respuesta usando el criterio RECIST 1.1 modificado para pacientes a evaluar.
    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 Yes
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    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 concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA60
    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
    Israel
    Korea, Republic of
    Netherlands
    Spain
    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 last visit of the last patient undergoing the study
    La última visita del último paciente en el estudio
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days30
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months0
    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: 70
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 75
    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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 145
    F.4.2.2In the whole clinical trial 145
    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)
    Once a patient has discontinued study treatment, clinic visits will be reduced to every 8 weeks. Following discontinuation of study treatment, further treatment will be at the discretion of the investigator however it is anticipated (but not required) that patients will be retreated with their platinum based regimen.
    Una vez que el paciente haya sido discontinuado del tratamiento del estudio, las visitas a la clínica se reducirán a cada 8 semanas.Tras la interrupción del tratamiento del estudio, se administrarán otros tratamientos a discreción del investigador. Sin embargo se prevé (aunque no es requerido) que los pacientes sean tratados de nuevo con su régimen basado en platino.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2014-11-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-11-04
    P. End of Trial
    P.End of Trial StatusOngoing
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