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    Summary
    EudraCT Number:2014-000336-42
    Sponsor's Protocol Code Number:D4191C00001
    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:2014-07-22
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2014-000336-42
    A.3Full title of the trial
    A Phase III, Randomised, Double-blind, Placebo-controlled, Multi-centre, International Study of MEDI4736 as Sequential Therapy in Patients with Locally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III) Who Have Not Progressed Following Definitive, Platinum-based, Concurrent Chemoradiation Therapy (PACIFIC)
    Estudio internacional multicéntrico de fase III, aleatorizado, doble ciego, controlado con placebo, de MEDI4736 como tratamiento secuencial en pacientes con cáncer pulmonar de células no pequeñas, localmente avanzado, no resecable (estadio III) que no han progresado después de una terapia de quimiorradiación concurrente definitiva con base de platino (PACIFIC)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase III Study of MEDI4736 as Sequential Therapy in Patients with Locally Advanced Non-Small Cell Lung Cancer
    Estudio fase III de MEDI4736 como tratamiento secuencial en pacientes con cáncer pulmonar de células no pequeñas
    A.3.2Name or abbreviated title of the trial where available
    PACIFIC
    PACIFIC
    A.4.1Sponsor's protocol code numberD4191C00001
    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 AB
    B.5.2Functional name of contact pointInformation Centre
    B.5.3 Address:
    B.5.3.1Street AddressSödertälje
    B.5.3.2Town/ citySödertälje
    B.5.3.3Post codeSE 151 85
    B.5.3.4CountrySweden
    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 nameMEDI4736
    D.3.2Product code MEDI4736
    D.3.4Pharmaceutical form Lyophilisate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMEDI4736
    D.3.9.1CAS number 1428935-60-7
    D.3.9.2Current sponsor codeMEDI4736
    D.3.9.3Other descriptive nameMEDI4736
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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 Yes
    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 placeboSolution for injection
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Locally Advanced, Unresectable Non-Small Cell Lung Cancer (Stage III)
    Cáncer pulmonar de células no pequeñas, localmente avanzado, no resecable (estadio III)
    E.1.1.1Medical condition in easily understood language
    Non-Small Cell Lung Cancer
    Cáncer pulmonar de células no pequeñas
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    E.1.2Level LLT
    E.1.2Classification code 10066490
    E.1.2Term Progression of non-small cell lung cancer
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 17.0
    E.1.2Level LLT
    E.1.2Classification code 10029514
    E.1.2Term Non-small cell lung cancer NOS
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To assess the efficacy of MEDI4736 treatment compared with placebo in terms of OS and PFS
    Evaluar la eficacia de MEDI4736 compatado con placebo en terminos de supervivencia general (SP) y Supervivencia sin progresion SPP
    E.2.2Secondary objectives of the trial
    - To further assess the efficacy of MEDI4736 compared with placebo in terms of: OS24, ORR, DoR, APF12, APF18, PFS2 and DSR
    - To assess the safety and tolerability profile of MEDI4736 compared with placebo
    - To assess symptoms and health-related quality of life in patients treated with MEDI4736 compared with placebo
    -Evaluar aún más la eficacia de MEDI4736, en comparación con placebo, en cuanto a: SG24, TRO, DdR, VSP12, VSP18, SSP2 y RMP
    -Evaluar el perfil de seguridad y tolerabilidad de MEDI4736 en comparación con placebo
    -Explorar los síntomas y la calidad de vida relacionada con la salud en los pacientes tratados con MEDI4736, en comparación con placebo, mediante EORTC-QLQ-C30 v.3 y LC13
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Pharmacogenetics Research
    Investigación Farmacogenetica
    E.3Principal inclusion criteria
    1. Provision of signed, written and dated informed consent prior to any study specific procedures
    2. Male or female aged 18 years or older
    3. Patients must have histologically- or cytologically-documented NSCLC who present with locally advanced, unresectable (Stage III) disease
    4. Patients must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy.
    5. Patients must have not progressed following definitive, platinumbased, concurrent chemoradiation therapy.
    6. Patients must provide an archival tumour sample.
    7. Life expectancy ?12 weeks
    8. World Health Organization (WHO) Performance Status of 0 or 1
    9. Evidence of post-menopausal status, or negative urinary or serum pregnancy test for female pre-menopausal patients.
    10. Adequate organ and marrow function
    1. Proporcionar un consentimiento informado firmado y fechado antes de realizar cualquier procedimiento del estudio.
    2. Ser varón o mujer y haber cumplido los 18 años.
    3. Los pacientes deben presentar CPNM histológica o citológicamente documentado localmente avanzado no resecable (estadio III)
    4. Los pacientes deben haber recibido al menos 2 ciclos de quimioterapia basada en platino concurrente con radioterapia.
    5. Los pacientes no deben haber sufrido progresión después de la quimiorradioterapia concurrente definitiva basada en platino.
    6. Los pacientes deben proveer una muestra tumoral
    7. Esperanza de vida ? 12 semanas.
    8. Estado general de 0 o 1 de la Organización Mundial de la Salud (OMS).
    9. Indicios de estado posmenopáusico, o resultado negativo de la prueba de embarazo en orina o en suero en el caso de pacientes premenopáusicas.
    10. Función adecuada de los órganos y la médula
    E.4Principal exclusion criteria
    1. Participation in another clinical study with an investigational product during the last 4 weeks
    2. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) clinical study or the follow-up period of an interventional study
    3. Mixed small cell and non-small cell lung cancer histology
    4. Receipt of sequential chemoradiation therapy for locally advanced NSCLC
    5. Patients with locally advanced NSCLC who have progressed whilst receiving definitive platinum based, concurrent chemoradiation therapy
    6. Receipt of any immunotherapy, or investigational drug within 4 weeks prior to the first dose of study drug
    7. Current or prior use of immunosuppressive medication within 28 days before the first dose of study drug, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid. Systemic steroid administration required to manage toxicities arising from radiation therapy delivered as part of the chemoradiation therapy for locally advanced NSCLC is allowed.
    8. Prior exposure to any anti-PD-1 or anti-PD-L1 antibody
    9. Any unresolved toxicity CTCAE >Grade 2 from the prior chemoradiation therapy.
    10. Patients with irreversible toxicity that is not reasonably expected to be exacerbated by study drug may be included (eg, hearing loss) after consultation with the AstraZeneca/MedImmune medical monitor.
    11. Patients with any grade pneumonitis from prior chemoradiation therapy
    12. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment.
    13. Recent major surgery within 4 weeks
    14. Active or prior documented autoimmune disease within the past 2 years, except for: Vitiligo, Grave's disease, or psoriasis not requiring systemic treatment
    15. Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis)
    16. History of primary immunodeficiency
    17. History of allogeneic organ transplant
    18. History of hypersensitivity to MEDI4736 or any excipient
    19. Uncontrolled intercurrent illness
    20. Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving study drug.
    21. History of another primary malignancy within 5 years prior to starting study drug, except for adequately treated basal or squamous cell carcinoma of the skin or cancer of the cervix in situ and the disease under study
    22. Female patients who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing an effective method of birth control
    23. Any condition that, in the opinion of the investigator, would interfere with evaluation of the study drug or interpretation of patient safety or study results.
    1. Participación en otro estudio clínico con un producto en investigación durante las últimas 4 semanas
    2. Inscripción simultánea en otro estudio clínico, a menos que sea un estudio clínico observacional (no intervencionista) o el período de seguimiento de un estudio de intervención
    3. Histología mixta de cáncer pulmonar de células no pequeñas y de células pequeñas
    4. Pacientes que reciben un tratamiento con quimiorradiación secuencial para un CPNM en estadio localmente avanzado
    5. Pacientes con CPNM en estadio localmente avanzado que hayan progresado durante el tratamiento con quimiorradiación concurrente definitivo basado en platino
    6. Haber recibido una inmunoterapia o un fármaco en investigación en las 4 semanas anteriores a la primera dosis del fármaco del estudio; y, en el caso de anticuerpos monoclonales, 6 semanas antes de la primera dosis del fármaco del estudio
    7. El uso actual o anterior de medicación inmunodepresora en los 28 días antes de la primera dosis del fármaco del estudio, con la excepción de corticoesteroides intranasales e inhalados o corticoesteroides sistémicos a dosis fisiológicas que no deben superar los 10 mg/día de prednisona o un corticoesteroide equivalente. Se permite la administración necesaria de esteroides sistémicos para tratar las toxicidades derivadas de la radioterapia administrada como parte del tratamiento de quimiorradiación para el CPNM localmente avanzado
    8. Exposición anterior a algún anticuerpo PD-1 o anti-PD-L1
    9. Cualquier toxicidad sin resolver de grado > 2 según los CTCAA de la quimiorradioterapia anterior.
    10. Pacientes con toxicidad irreversible, que no se espera razonablemente que se agudice por el fármaco del estudio (p. ej., pérdida de audición), previa consulta con el supervisor médico de AstraZeneca/MedImmune
    11. Pacientes con neumonitis de cualquier grado por la quimiorradioterapia anterior
    12. Cualquier quimioterapia, inmunoterapia, tratamiento biológico u hormonal concurrentes para el tratamiento del cáncer.
    13. Cirugía mayor reciente en las 4 semanas antes de la entrada en el estudio
    14. Enfermedad autoinmunitaria, activa o documentada con anterioridad, en los últimos 2 años. NOTA: No están excluidos los pacientes con vitiligo, la enfermedad de Graves o psoriasis que no requieren un tratamiento sistémico (en los últimos 2 años)
    15. Enteropatía inflamatoria activa o documentada con anterioridad (p. ej. enfermedad de Crohn o colitis ulcerosa)
    16. Antecedentes de inmunodeficiencia primaria
    17. Antecedentes de trasplante de órganos que requieran inmunodepresión terapéutica
    18. Antecedentes de hipersensibilidad a MEDI4736 o cualquier excipiente
    19. Enfermedad intercurrente no controlada24. Antecedentes conocidos de tuberculosis
    20. Haber recibido una vacuna viva atenuada en los 30 días antes de la entrada en el estudio o en los 30 días antes de recibir el fármaco del estudio
    21. Antecedentes de otra neoplasia maligna primaria en los 5 años anteriores al comienzo del fármaco del estudio, a excepción del cáncer basocelular o escamocelular de la piel o del cáncer cervicouterino in situ, adecuadamente tratados, y de la enfermedad en estudio
    22. Pacientes que estén embarazadas o en período de lactancia, u hombres y mujeres con capacidad reproductiva que no utilicen un método anticonceptivo eficaz
    23. Cualquier trastorno que, en opinión del investigador, podría interferir en la evaluación del fármaco del estudio o la interpretación de la seguridad del paciente o de los resultados del estudio
    E.5 End points
    E.5.1Primary end point(s)
    Both Progression free survival (PFS) and Overall survival (OS) are co-primary endpoints.
    Tanto la supervivencia sin progresión (SSP) y la supervivencia general (SG) son criterios de valoración co-primarios.
    E.5.1.1Timepoint(s) of evaluation of this end point
    OS - Overall Survival is defined as the time from the date of randomization until death due to any cause. Estimated to be from baseline up to 5 years.
    PFS - Progression-Free Survival is defined as the time from randomization until the date of objective disease progression or death. Estimated to be from baseline up to 5 years.
    SG - Supervivencia global se define como el tiempo desde la fecha de la asignación al azar hasta la muerte por cualquier causa. Se estima que es desde la línea base hasta 5 años.
    PSS - supervivencia sin progresión se define como el tiempo desde la aleatorización hasta la fecha de progresión objetiva de la enfermedad o la muerte. Se estima que es hasta 5 años
    E.5.2Secondary end point(s)
    - Proportion of patients alive at 24 months from randomization (OS24)
    - Objective response rate (ORR)
    - Proporción de pacientes vivos a los 24 meses desde la aleatorización (SG24)
    - Tasa de respuesta objetiva (TRO)
    E.5.2.1Timepoint(s) of evaluation of this end point
    - OS24: The proportion of patients alive at 24 months. Estimated to be from baseline up to 5 years.
    - ORR: Defined as the number (%) of patients with at least 1 visit response of CR (Complete response) or PR (Partial response) and will be based on all randomised patients who have measurable disease. Study data collection expected to last for approximately 3 years.
    - SG24: La proporción de pacientes vivos a los 24 meses. Se estima que es desde la a base hasta 5 años.
    - TRO: Se define como el número (%) de pacientes con al menos 1 visita respuesta de RC (respuesta completa) o PR (respuesta parcial) y se basará en todos los pacientes asignados al azar que tienen enfermedad medible. La recopilación de datos de estudios prevé una duración de aproximadamente 3 años.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic 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 concerned11
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA118
    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
    Argentina
    Australia
    Brazil
    Canada
    Chile
    China
    Colombia
    European Union
    Hong Kong
    Japan
    Korea, Republic of
    Malaysia
    Mexico
    New Zealand
    Panama
    Peru
    Philippines
    Russian Federation
    Serbia
    Singapore
    South Africa
    Spain
    Taiwan
    Thailand
    Turkey
    Ukraine
    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 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 sujeto del estudio
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months6
    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: 484
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 396
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 298
    F.4.2.2In the whole clinical trial 880
    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)
    Treatment from Day 1 for a maximum of 12 months or study drug withdrawal if this occurs earlier.
    Tratamiento desde el Día 1 para un máximo de 12 meses o retirada del fármaco del estudio si se produce antes ..
    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 Decision2014-10-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2014-10-06
    P. End of Trial
    P.End of Trial StatusOngoing
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