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    Summary
    EudraCT Number:2017-002767-17
    Sponsor's Protocol Code Number:D0816C00020
    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:2017-12-21
    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 number2017-002767-17
    A.3Full title of the trial
    A Phase IIIb, Single-arm, Open-label Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed non-Germline BRCA Mutated Ovarian Cancer Patients who are in Complete or Partial Response Following Platinum based Chemotherapy.
    OPINIÓN - Estudio en fase IIIb, abierto, de grupo único y multicéntrico de la monoterapia de mantenimiento con olaparib en pacientes con cáncer de ovario recidivante sin mutación de BRCA en línea germinal y sensible al platino que están en respuesta parcial o completa tras la quimioterapia con platino
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase IIIb, Single-arm, Open-label Multicentre Study of Olaparib Maintenance Monotherapy in Platinum Sensitive Relapsed non-Germline BRCA Mutated Ovarian Cancer Patients who are in Complete or Partial Response Following Platinum based Chemotherapy
    OPINIÓN - Estudio en fase IIIb, abierto, de grupo único y multicéntrico de la monoterapia de mantenimiento con olaparib en pacientes con cáncer de ovario recidivante sin mutación de BRCA en línea germinal y sensible al platino que están en respuesta parcial o completa tras la quimioterapia con platino
    A.3.2Name or abbreviated title of the trial where available
    OPINION
    OPINION
    A.4.1Sponsor's protocol code numberD0816C00020
    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.5.6E-mailinformation.center@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.3.9.2Current sponsor codeAZD2281
    D.3.9.3Other descriptive nameOLAPARIB
    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.3.9.2Current sponsor codeAZD2281
    D.3.9.3Other descriptive nameOLAPARIB
    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 Germline BRCA Mutated Ovarian Cancer
    Cáncer de ovario BRCA germinal no mutado
    E.1.1.1Medical condition in easily understood language
    Ovarian cancer
    Cáncer de ovario
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10033128
    E.1.2Term Ovarian 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 determine the efficacy by progression-free survival (PFS) (investigator-recorded assessments according to modified Response Evaluation Criteria In Solid Tumors [RECIST v1.1]) of olaparib maintenance monotherapy in non gBRCAm platinum sensitive relapsed (PSR) ovarian cancer
    Determinar la eficacia de la supervivencia libre de progresión (SLP) (evaluaciones registradas por el investigador según criterios de evaluación de respuesta modificados en tumores sólidos [RECIST v1.1]) de monoterapia de mantenimiento con olaparib en cáncer de ovario no recurrente sensible a platino (PSR) no gBRCAm
    E.2.2Secondary objectives of the trial
    - Determine efficacy of olaparib maintenance monotherapy in non gBRCAm PSR ovarian cancer by assessment of time to first subsequent therapy or death (TFST)
    - Determine efficacy of olaparib maintenance monotherapy in non gBRCAm PSR ovarian cancer by assessment of time to treatment discontinuation or death (TDT)
    - Determine efficacy by PFS of olaparib maintenance in non gBRCAm PSR ovarian cancer according to tumour HRD status using the Myriad myChoice HRD test
    - Determine efficacy of olaparib maintenance monotherapy in non gBRCAm PSR ovarian cancer by assessment of chemotherapy-free interval (CT-FI)
    - To investigate the Health-related Quality of Life (HRQoL) of non gBRCAm PSR ovarian cancer patients treated with olaparib maintenance monotherapy as assessed by the trial outcome index (TOI) of the Functional Assessment of Cancer Therapy – Ovarian (FACT-O)

    - To assess the safety and tolerability of olaparib maintenance monotherapy in patients with non gBRCAm PSR ovarian cancer
    Determinar la eficacia de olaparib en cáncer de ovario no gBRCAm mediante la evaluación del tiempo hasta la primera terapia posterior o muerte
    Determinar la eficacia de olaparib en cáncer de ovario no gBRCAm mediante la evaluación del tiempo transcurrido hasta la interrupción del tratamiento o muerte
    Determinar la eficacia de olaparib en cáncer de ovario no gBRCAm PSR según el estado del HRD del tumor mediante la prueba Myriad myChoice
    Determinar la eficacia de olaparib en cáncer de ovario no gBRCAm PSR mediante la evaluación del intervalo sin quimioterapia
    Investigar la calidad de vida relacionada con la salud (CVRS) de pacientes con cáncer de ovario no gBRCAm tratados con monoterapia de olaparib evaluada mediante el índice de resultado del ensayo (TOI) de la evaluación funcional de la terapia del cáncer ovárico (FACT-O)
    Evaluar la seguridad y la tolerabilidad de olaparib en pacientes con cáncer de ovario sin GBRCAm PSR
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Provision of informed consent prior to any study specific procedures
    2. Patients must be ≥18 years of age
    3. Female patients with histologically diagnosed relapsed HGSOC (including primary peritoneal and / or fallopian tube cancer) or high grade endometrioid cancer
    4. Documented gBRCA1/2 mutation status Evidence that the patients do not have a gBRCA mutation that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental / lead to loss of function). gBRCA1 and/or gBRCA2 variants that are classified as
    "Variants of uncertain clinical significance" or "Variant of unknown significance (VUS)" are eligible, as well as "Variant, favor polymorphism" or "benign polymorphism".
    Evidence of the absence of a somatic BRCA mutation is not required.
    Patients with a tumour BRCA test result only must undergo a gBRCA test to determine whether the BRCA aberration is germline or somatic in origin. If this analysis identifies the aberration as germline the patient is not eligible
    5. Patients must have completed at least 2 previous courses of platinum containing therapy:
    (a) For the penultimate chemotherapy course prior to enrolment on the study:
    • Treatment must have contained a platinum agent (e.g. carboplatin or cisplatin per standard clinical practice; there are no other specific requirements)
    • Patient was platinum sensitive after this treatment; defined as disease progression greater than 6 months after completion of their last dose of platinum chemotherapy
    • Maintenance treatment is allowed at the end of the penultimate platinum regimen, including bevacizumab
    (b) For the last chemotherapy course immediately prior to enrolment on the study
    • Patients must be, in the opinion of the investigator, in response (partial or complete radiological response), or may have no evidence of disease (if optimal cytoreductive surgery was conducted prior to chemotherapy), and no evidence of a rising CA-125, as defined below, following completion of this chemotherapy course
    • Patient must have received a platinum based chemotherapy regimen (carboplatin or cisplatin) and have received at least 4 cycles of treatment
    • Patients must not have received bevacizumab during this course of treatment
    • Patients must not have received any investigational agent during this course of treatment
    • Patients must initiate treatment within 8 weeks of their last dose of chemotherapy (last dose is the day of the last infusion)
    6. Pre-treatment CA-125 measurements must meet criterion specified below:
    • If the first value is within upper limit of normal (ULN) the patient is eligible to be enrolled and a second sample is not required
    • If the first value is greater than ULN a second assessment must be performed at least 7 days after the 1st. If the second assessment is ≥ 15% more than the first, the patient is not eligible
    7. Patients must have normal organ and bone marrow function measured within 28 days of starting study treatment, as defined below. In the event of minor deviations from these values which would lead to screen failure, repeat testing within the 28-day screening period (limited to the tests listed below) is allowed before the patient is declared a screen failure.
    8. ECOG performance status 0-1
    9. Patients must have a life expectancy ≥16 weeks
    10. Postmenopausal or evidence of non-childbearing status for women of childbearing potential :negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on day 1
    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. At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline with computed tomography (CT) or magnetic resonance imaging (MRI) and is suitable for repeated assessment
    OR
    No evidence of disease following a complete response to chemotherapy (with or without cytoreductive surgery)
    13. An appropriately prepared tumour sample from the cancer, of sufficient quantity and quality (as specified in the Central Laboratory Services Manual) must be available for future central testing of tumour genetic status. If a recent biopsied sample is provided, the biopsied tumour should not be assessed as target lesions as part of the RECIST assessments if there are other lesions available, and the biopsy should be taken after the baseline scan has been performed. Archival tissue samples may be from the primary tumour or metastatic tumour deposits. Archival bone metastases are not acceptable. Provision of blocks is usually preferred. Any exceptions to these conditions should be discussed with the Sponsor before enrollment of the patient.
    Obtener el consentimiento informado antes de cualquier procedimiento estudio
    Los pacientes deben tener ≥18 años de edad
    Pacientes mujeres con HGSOC recidivada histológicamente (incluido cáncer peritoneal primario y / o trompas de Falopio) o cáncer endometrioide de alto grado
    Estado documentado de la mutación gBRCA1/2 Evidencia de que los pacientes no tienen una mutación gBRCA que se predice es perjudicial o que se sospecha que sea. gBRCA1 y/o gBRCA2 variantes que se clasifican como: Variantes de significado clínico incierto" o "Variante de significado desconocido" son elegibles, así como "Variante, polimorfismo favorable" o "polimorfismo benigno". No se requiere evidencia de la ausencia de una mutación BRCA somática. Pacientes con un resultado de prueba de tumor BRCA solo deben someterse a una prueba de gBRCA para determinar si la mutación BRCA es de origen germinal o somático. Si este análisis identifica mutación en línea germinal, el paciente no es elegible
    Pacientes deben haber completado al menos 2 cursos anteriores de terapia con platino:
    (a)Para el penúltimo curso de quimioterapia antes de la inscripción en el estudio:El tratamiento debe contener un agente de platino (por ejemplo, carboplatino o cisplatino según la práctica clínica habitual, no existen otros requisitos específicos)El paciente era sensible al platino después de este tratamiento; definida como progresión de la enfermedad más de 6 meses después de completar su última dosis de quimioterapia con platino. Se permite el tratamiento de mantenimiento al final del penúltimo régimen de platino, incluido bevacizumab
    (b) Para el último curso de quimioterapia inmediatamente antes de la inscripción en el estudio: Los pacientes deben ser, en opinión del investigador, en respuesta (respuesta radiológica parcial o completa), o pueden no tener evidencia de enfermedad (si se realizó una cirugía citorreductora óptima antes de la quimioterapia), y no hay evidencia de una CA-125 en aumento, como se define a continuación: El paciente debe haber recibido un régimen de quimioterapia basado en platino (carboplatino o cisplatino) y haber recibido al menos 4 ciclos de tratamiento. Los pacientes no deben haber recibido bevacizumab durante este curso de tratamiento. Los pacientes no deben haber recibido ningún agente de investigación durante este curso de tratamiento. Los pacientes deben iniciar el tratamiento dentro de las 8 semanas de su última dosis de quimioterapia (la última dosis es el día de la última infusión). Las mediciones de CA-125 previas al tratamiento deben cumplir el criterio especificado a continuación: Si el primer valor está dentro del límite superior de lo normal (ULN), el paciente es elegible para inscribirse y no se requiere una segunda muestra. Si el primer valor es mayor que ULN, se debe realizar una segunda evaluación al menos 7 días después del 1er. Si la segunda evaluación es ≥ 15% más que la primera, el paciente no es elegible. Los pacientes deben tener la función normal de la médula ósea y del órgano medida dentro de los 28 días posteriores al inicio del tratamiento del estudio, tal como se define a continuación. En el caso de desviaciones menores de estos valores que pudieran provocar fallas en la pantalla, se permite repetir las pruebas dentro del período de detección de 28 días antes de que se declare al paciente como una falla en la pantalla.
    Estado de funcionamiento del ECOG 0-1
    Pacientes deben tener una expectativa de vida ≥16 semanas
    Posmenopausia o evidencia de estado de no embarazo para mujeres en edad fértil: prueba de embarazo negativa en orina o suero dentro de los 28 días del tratamiento del estudio y confirmada antes del tratamiento en el día 1
    Paciente está dispuesto y es capaz de cumplir con el protocolo durante la duración del estudio, incluido el tratamiento y las visitas y exámenes programados.
    Al menos una lesión (mensurable y / o no mensurable) que pueda evaluarse con precisión al inicio del estudio con tomografía computarizada (TC) o resonancia magnética (RM) y sea adecuada para evaluación repetida. O, No hay evidencia de enfermedad luego de una respuesta completa a la quimioterapia (con o sin cirugía citorreductora)
    Una muestra tumoral adecuadamente preparada del cáncer, de suficiente cantidad y calidad (como se especifica en el Manual de servicios del laboratorio central) debe estar disponible para futuras pruebas centrales del estado genético tumoral. Si se proporciona una muestra de biopsia reciente, el tumor sometido a biopsia no debe evaluarse como lesiones diana como parte de las evaluaciones RECIST si hay otras lesiones disponibles, y la biopsia se debe tomar después de que se haya realizado la exploración inicial. Las muestras de tejido de archivo pueden ser del tumor primario o depósitos de tumores metastásicos. Metástasis óseas de archivo no son aceptables. Bloques es usualmente preferida. Cualquier excepción a estas condiciones debe discutirse con el Promotor antes de la inscripción.
    E.4Principal exclusion criteria
    Patients should not enter the study if any of the following exclusion criteria are fulfilled.
    Those asterisked* should be excluded before a request can be considered to perform a gBRCA test prior to full screening. Investigator judgement of patient's potential eligibility to the study should be
    assessed as per Protocol Table 1 and by reviewing the below exclusion criteria).

    1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)*
    2. Previous enrolment in the present study*
    3. Participation in another clinical study with an investigational product (IP) during the most recent chemotherapy course*
    4. Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) within 3 weeks prior to start of study treatment
    5. Any previous treatment with PARP inhibitor, including olaparib*
    6. Patients with a germline BRCA mutation that is predicted to be deleterious or suspected deleterious (known or predicted to be detrimental / lead to loss of function).
    7. Other malignancy within the last 5 years except: adequately treated non-melanoma 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 ≥5 years*
    8. Concomitant use of known strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g., ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting olaparib is 2 weeks*.
    9. Concomitant use of known strong (e.g., phenobarbital, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g., bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5
    weeks for phenobarbital and 3 weeks for other agents*
    10. Persistent toxicities (≥ Grade 2 Common Terminology Criteria for Adverse Event (CTCAE) adverse event) caused by previous cancer therapy, excluding alopecia
    11. Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML*
    12. Patients with symptomatic uncontrolled brain metastases. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have
    received definitive treatment for this and evidence of clinically stable disease (SD) for 28 days*
    13. Major surgery within 3 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
    14. Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection.
    15. Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication*
    16. Currently pregnant (confirmed with a positive pregnancy test) or breastfeeding women*
    17. Immuno-compromised patients e.g., Human Immunodeficiency Virus (HIV) requiring treatment or active Hepatitis B or C*
    18. Patients with a known hypersensitivity to olaparib or any of the excipients of the product*
    19. Patients with known active hepatitis (i.e., hepatitis B or C) due to risk of transmitting the infection through blood or other body fluids*
    20. Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)*
    21. Patients having gBRCA testing should not have had whole blood transfusions in the last 30 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable)
    22. Judgement by the Investigator that the patient should not participate in the study if the patient is unlikely or unable to comply with study procedures, restrictions and requirements.
    Participación en planificación y/o realización del estudio (se aplica tanto al personal de AstraZeneca como al personal del sitio de estudio)*
    Inscripción previa en el presente estudio*
    Participación en otro estudio clínico con un producto en investigación durante el curso de quimioterapia más reciente*
    Pacientes que reciben cualquier quimioterapia sistémica o radioterapia (excepto por razones paliativas) dentro de las 3 semanas anteriores al inicio del tratamiento del estudio
    Cualquier tratamiento previo con inhibidor de PARP, incluido olaparib *
    Pacientes con mutación BRCA en la línea germinal que se predice que es perjudicial o se sospecha que es nociva
    Otras neoplasias malignas en los últimos 5 años excepto: cáncer de piel no melanoma adecuadamente tratado, cáncer de cuello uterino in situ tratado curativamente, carcinoma ductal in situ (DCIS), carcinoma endometrial en estadio 1, grado 1 u otros tumores sólidos, incluidos los linfomas (sin hueso afectación de la médula ósea) tratado curativamente sin evidencia de enfermedad por> 5 años*
    Uso concomitante de inhibidores de CYP3A fuertes conocidos (por ejemplo, itraconazol, telitromicina, claritromicina, inhibidores de proteasa potenciados con ritonavir o cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) o inhibidores moderados de CYP3A (p. Ej., Ciprofloxacina, eritromicina, diltiazem, fluconazol , verapamilo). El período de lavado requerido antes de comenzar olaparib es de 2 semanas *.
    Uso concomitante de fuertes conocidos (p. Ej., Fenobarbital, fenitoína, rifampicina, rifabutina, rifapentina, carbamazepina, nevirapina y hierba de San Juan) o inductores moderados de CYP3A (p. Ej., Bosentán, efavirenz, modafinilo). El período de lavado requerido antes de comenzar olaparib es 5
    semanas para el fenobarbital y 3 semanas para otros agentes*
    Toxicidades persistentes (≥ Grado 2 Criterios de terminología común para eventos adversos del evento adverso (CTCAE)) causadas por la terapia previa contra el cáncer, excluida la alopecia
    Pacientes con síndrome mielodisplásico (SMD) / leucemia mieloide aguda o con características sugestivas de SMD / AML*
    Pacientes con metástasis cerebrales sin control sintomático. El paciente puede recibir una dosis estable de corticosteroides antes y durante el estudio, siempre que estos se hayan iniciado al menos 4 semanas antes del tratamiento. Pacientes con compresión de la médula espinal a menos que se considere que tienen recibió tratamiento definitivo para esto y evidencia de enfermedad clínicamente estable (DE) durante 28 días*
    Cirugía mayor dentro de las 3 semanas posteriores al inicio del tratamiento del estudio y los pacientes deben haberse recuperado de los efectos de cualquier cirugía mayor
    Los pacientes consideraron un riesgo médico deficiente debido a un trastorno médico serio e incontrolable, una enfermedad sistémica no maligna o una infección activa e incontrolada.
    Pacientes incapaces de tragar medicamentos administrados por vía oral y pacientes con trastornos gastrointestinales que pueden interferir con la absorción de la medicación del estudio*
    Actualmente embarazada (confirmada con una prueba de embarazo positiva) o mujeres lactantes*
    Pacientes inmunocomprometidos, p. Ej., Virus de Inmunodeficiencia Humana que requieren tratamiento o Hepatitis B o C activa
    Pacientes con hipersensibilidad conocida a olaparib o cualquiera de los excipientes del producto*
    Pacientes con hepatitis activa conocida (es decir, hepatitis B o C) debido al riesgo de transmitir la infección a través de sangre u otros líquidos corporales*
    Trasplante alogénico previo de médula ósea o trasplante doble de cordón umbilical (dUCBT)*
    Los pacientes que tienen pruebas de gBRCA no deberían haber recibido transfusiones de sangre completa en los últimos 30 días antes de ingresar al estudio (es posible que se transfieran glóbulos rojos concentrados y transfusiones de plaquetas).
    Juicio del investigador de que el paciente no debe participar en el estudio si el paciente es poco probable o no puede cumplir con los procedimientos, restricciones y requisitos del estudio.
    E.5 End points
    E.5.1Primary end point(s)
    PFS: Time from date of first dose until the date of objective radiological disease progression according to modified RECIST 1.1 or death (by any cause in the absence of progression)
    PFS: tiempo desde la fecha de la primera dosis hasta la fecha de progresión radiológica objetiva de la enfermedad de acuerdo con RECIST 1.1 modificado o muerte (por cualquier causa en ausencia de progresión)
    E.5.1.1Timepoint(s) of evaluation of this end point
    At visit 4 and on the first day of each 8 week visit period, relative to the date of the first olaparib dose, for the first 12 months on treatment, and subsequently each 12-week visit period, until the earlier of progression, death or end of study for up to 30 months.
    En la visita 4 y el primer día de cada período de visita de 8 semanas, en relación con la fecha de la primera dosis de olaparib, durante los primeros 12 meses de tratamiento, y posteriormente cada período de visita de 12 semanas, hasta el momento de la progresión, muerte o fin del estudio por hasta 30 meses.
    E.5.2Secondary end point(s)
    (1) - TFST: Time from date of first dose to date of first subsequent treatment commencement or death due to any cause if this occurs before commencement of first subsequent treatment
    (2) - TDT: Time from date of first dose to date of study drug discontinuation or death due to any cause if this occurs before study drug discontinuation
    (3) - PFS in the following subgroups:
    1. Somatic BRCA mutated and HRD scar positive;
    2. HRD scar positive, non-BRCA mutated;
    3. HRD scar negative, non-BRCA mutated
    (4) - CT-FI: Time from the date of the last dose of platinum chemotherapy prior to olaparib maintenance therapy until the date of initiation of the next anticancer therapy
    (5) - Proportion of patients with any improvement from baseline in TOI score
    (6) - Proportion of patients with a 10 point deterioration from baseline in TOI score
    (7) - AE/SAE. Collection of clinical chemistry/haematology parameters.
    (1) - TFST: tiempo desde la fecha de la primera dosis hasta la fecha del primer inicio del tratamiento posterior o muerte por cualquier causa si esto ocurre antes del comienzo del primer tratamiento posterior
    (2) - TDT: tiempo desde la fecha de la primera dosis hasta la fecha de descontinuación del medicamento en estudio o muerte por cualquier causa si esto ocurre antes de la interrupción del estudio.
    (3) - PFS en los siguientes subgrupos:
    1. somático BRCA mutado y HRD cicatriz positiva;
    2. HRD cicatriz positiva, no-BRCA mutada;
    3. HRD cicatriz negativa, no-BRCA mutado
    (4) - CT-FI: tiempo transcurrido desde la fecha de la última dosis de quimioterapia con platino antes de la terapia de mantenimiento con olaparib hasta la fecha de inicio de la siguiente terapia contra el cáncer
    (5) - Proporción de pacientes con cualquier mejora desde el inicio en la puntuación TOI
    (6) - Proporción de pacientes con un deterioro de 10 puntos desde el inicio en la puntuación TOI
    (7) - AE / SAE. Colección de parámetros de química / hematología clínica.
    E.5.2.1Timepoint(s) of evaluation of this end point
    (1) (2) - TFST/TDT : visit 2, 3, 4 and at every tumor assessment visit (TAV), at discontinuation of study drug, at 30 days post last dose, every 12 weeks during long term FUP (up to 30 months)
    (3) - visit 4 and every 8 week for the first 12 months, and each 12 week until earlier progression, death or EOS for up to 30 months
    (4) - Screening, Visit 2, 3, 4 and subsequent TAV, Visit 5 and subsequent safety visits (SV) (at day 85 and then every 8 weeks), until 30 days after last dose and then every 12 weeks until EOS (for up to 30 months)
    (5 and 6) - Visit 2, 3, 4 and at every TAV until progression, at discontinuation of study drug visit and at 30 days post last dose
    (7) - Screening, Visit 2, 3, 4 and subsequent TAV , Visit 5 and subsequent SV, until 30 days after last dose of study drug
    (1)(2) TFST/TDT: visita 2, 3, 4 y en cada visita de evaluación tumoral, a la interrupción del fármaco del estudio, 30 días después de la última dosis, cada 12 semanas durante FUP a largo plazo (hasta 30 meses) (3) visita 4 y cada 8 semanas durante 12 meses, y cada 12 semanas hasta una progresión, muerte o EOS por hasta 30 meses (4) Examen, Visita 2, 3, 4 y posterior TAV, Visita 5 y visitas de seguridad posteriores (al día 85 y luego cada 8 semanas), hasta 30 días después de la última dosis y luego cada 12 semanas hasta EOS (hasta 30 meses) (5 y 6): visita 2, 3, 4 y en cada VTA hasta la progresión, al suspender el medicamento del estudio y a los 30 días después de la última dosis (7) Examen, Visita 2, 3, 4 y posterior TAV, visita 5 y posterior SV, hasta 30 días después de la última dosis.
    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 No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) 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 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 EEA52
    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
    Austria
    Belgium
    Canada
    Czech Republic
    Denmark
    Finland
    Israel
    Italy
    Japan
    Netherlands
    Norway
    Poland
    Portugal
    Romania
    Slovenia
    Spain
    Sweden
    Switzerland
    United Kingdom
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of the study is defined as 'the last visit of the last patient undergoing the study'.
    El final del estudio se define como "la última visita del último paciente que se sometió al estudio".
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months10
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months10
    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: 113
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 137
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    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 state10
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 198
    F.4.2.2In the whole clinical trial 250
    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)
    AstraZeneca will continue to supply drug to patients who are deemed to be obtaining benefit by their treating physician.
    120/5000
    AstraZeneca continuará suministrando medicamentos a pacientes que el médico tratante considere que están obteniendo beneficios.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    G.4.1Name of Organisation Nordic Society of Gyn Oncology (NSGO)
    G.4.3.4Network Country Denmark
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-01-30
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-01-29
    P. End of Trial
    P.End of Trial StatusOngoing
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