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    Summary
    EudraCT Number:2017-003302-40
    Sponsor's Protocol Code Number:WO40242
    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:2018-03-13
    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 number2017-003302-40
    A.3Full title of the trial
    A PHASE III, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF ATEZOLIZUMAB (ANTIPD-L1 ANTIBODY) AS ADJUVANT THERAPY AFTER DEFINITIVE LOCAL THERAPY IN PATIENTS WITH HIGH-RISK LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK
    ESTUDIO FASE III, MULTICÉNTRICO, ALEATORIZADO, DOBLE CIEGO, CONTROLADO CON PLACEBO DE ATEZOLIZUMAB (ANTICUERPO ANTI-PD-L1) COMO TERAPIA ADYUVANTE TRAS TERAPIA LOCAL DEFINITIVA, EN PACIENTES CON CARCINOMA DE CABEZA Y CUELLO DE CÉLULAS ESCAMOSAS CON ALTO RIESGO LOCALMENTE AVANZADO.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Atezolizumab (Anti-PD-L1 Antibody) as Adjuvant Therapy after Definitive Local Therapy in Patients with High-Risk Locally Advanced Squamous Cell Carcinoma of the Head and Neck
    Estudio de Atezolizumab (anticuerpo Anti-PD-L1) como terapia adyuvante despues de terapia definitiva local en pacientes con carcinoma de cabeza y cuello de celulas escamosas con lato riesgo localmente avanzado
    A.4.1Sponsor's protocol code numberWO40242
    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 SponsorRoche Farma S.A.(Soc.Unipersonal)que realiza el ensayo en España y actúa como representante de F. Hoffmann-La Roche LTD
    B.1.3.4CountrySwitzerland
    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 supportF. Hoffmann-La Roche Ltd.
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF.Hoffmann-La Roche Ltd.
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.4Telephone number+34913257300
    B.5.6E-mailspain.start_up_unit@roche.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 nameAtezolizumab
    D.3.2Product code RO5541267/F03
    D.3.4Pharmaceutical form 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 INNATEZOLIZUMAB
    D.3.9.1CAS number 1380723-44-3
    D.3.9.2Current sponsor codeRO5541267
    D.3.9.3Other descriptive nameMPDL3280A, Tecentriq
    D.3.9.4EV Substance CodeSUB178312
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    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 infusion
    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 squamous cell carcinoma of the head and neck (SCCHN)
    Carcinoma localmente avanzado de células escamosas de la cabeza y el cuello (CCECC)
    E.1.1.1Medical condition in easily understood language
    Squamous cell carcinoma is a cancer that arises from particular cells called squamous cells and develops in the mucous membranes (lining) of the different structures in the mouth, throat, and larynx
    El carcinoma de células escamosas es un cáncer que aparece de llamadas células escamosas y que se desarrolla en las membranas mucosas de las diferentes estructuras de la boca, garganta y laringe
    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 10041823
    E.1.2Term Squamous cell carcinoma
    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 evaluate the efficacy of atezolizumab compared with placebo based on independent review facility (IRF)-assessed event free survival (EFS) and overall survival (OS)
    Evaluar la eficacia de atezolizumab en comparación con un placebo basada en un centro de revisión independiente (CRI) y evaluada por supervivencia libre de eventos (SLE) y supervivencia global (SG)
    E.2.2Secondary objectives of the trial
    •To evaluate the efficacy of atezolizumab compared with placebo based on Investigator-assessed EFS, IRF and investigator-assessed EFS at 1 and 2 years and OS at 1, 2, and 3 years
    •To evaluate clinical benefit in atezolizumab compared with placebo in terms of impact on health-related quality of life and physical functioning
    •To evaluate the safety and tolerability of atezolizumab
    •To characterize the pharmacokinetics of atezolizumab
    •To evaluate the incidence and titers of anti-drug antibody(ADA) against atezolizumab
    •Evaluar la eficacia de atezolizumab en comparación con un placebo basada en supervivencia libre de eventos (SLE) evaluada por el investigador, CRI y en supervivencia libre de eventos evaluada por el investigador al año y los dos años y SG al año, dos y tres años
    •Evaluar el beneficio clínico de atezolizumab en comparación con un placebo en lo que se refiere a la repercusión sobre la CdVRS y la función física.
    •Evaluar la seguridad y tolerabilidad de atezolizumab
    •Caracterizar la farmacocinética de atezolizumab.
    •Evaluar la incidencia y los títulos de ACF contra atezolizumab
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -Age >= 18 years
    -Ability to comply with the study protocol, in the investigator's judgment
    -Histologically or cytologically confirmed SCCHN [Human papillomavirus (HPV) positive Stage III or HPV negative Stave IVA or IVB based on American Joint Committee on Cancer 8th Edition Cancer Staging Manual] involving the oral cavity, oropharynx, larynx, or hypopharynx
    •HPV negative Stage IVA (T3/T4a  N2M0) regardless of tobacco use history
    •HPV negative Stage IVB (T3/T4a  N3M0 or T4b  N2/N3M0) regardless of tobacco use history
    •HPV-positive oropharyngeal carcinoma Stage III (clinical T1/T2  N3M0) and >=10 years of tobacco use history
    •HPV-positive oropharyngeal carcinoma Stage III (clinical T3/T4  N3M0 or pathologic T3/T4  N2M0) regardless of tobacco use history
    - Human papillomavirus (HPV) status as determined locally by p16 immunohistochemistry, in situ hybridization, or by polymerase chain reaction-based assay
    -Completed definitive local therapy and have scans 10-12 weeks after completion of definitive local therapy confirming either complete response, partial response, or stable disease and within 4 weeks of randomization
    - Absence of metastatic disease as documented by radiographic scans
    - Recovered from acute toxicities, except fatigue, xerostomia, dysgeusia, alopecia, associated with definitive treatment to Grade 1 or lower
    - Patients with feeding tubes are eligible
    - Availability of a representative pretreatment tumor specimen for exploratory biomarker research
    - Eastern Cooperative Oncology Group performance status of 0 or 1
    - Life expectancy >= 12 weeks
    - Adequate hematologic and end-organ function
    - For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
    - Negative HIV test at screening
    - Negative hepatitis B surface antigen test at screening
    - Negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
    - Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
    - For women of childbearing potential: agreement to remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the last dose of study treatment
    -Edad ≥ 18 años
    ·-Capacidad para cumplir el protocolo del estudio, a criterio del investigador.
    -CCECC confirmado histológica o citológicamente (en estadio III y VPH positivo o en estadio IVA o IVB y VPH negativo, conforme a la 8.ª edición del Manual de Estadificación del Cáncer del AJCC) que afecte a la cavidad oral, la orofaringe, la laringe o la hipofaringe
    •Estadio IVA (T3/T4a + N2M0), VPH negativo, con independencia de los antecedentes tabáquicos.
    •Estadio IVB (T3/T4a + N3M0 o T4b + N2/N3M0), VPH negativo, con independencia de los antecedentes tabáquicos.
    •Carcinoma orofaríngeo en estadio III (T1/T2 clínica + N3M0), VPH positivo y consumo de tabaco ≥ 10 años.
    •Carcinoma orofaríngeo en estadio III (T3/T4 clínica + N3M0 o T3/T4 anatomopatológica + N2M0), VPH positivo, con independencia de los antecedentes tabáquicos
    -Determinación local de la presencia o ausencia de VPH mediante IHQ de p16, hibridación in situ o análisis basado en la reacción en cadena de la polimerasa.
    -Tratamiento local definitivo completado y pruebas de imagen efectuadas 10-12 semanas después del final del tratamiento local definitivo, en las 4 semanas siguientes a la aleatorización, que confirmen la presencia de RC, RP o EE.
    -Ausencia de enfermedad metastásica, documentada por radiología.
    -Recuperación hasta un grado 1 o menor de la toxicidad aguda asociada al tratamiento definitivo, excepto cansancio, xerostomía, disgeusia y alopecia.
    -Podrán participar pacientes con sondas de alimentación
    -Disponibilidad de una muestra tumoral representativa previa al tratamiento para la investigación de biomarcadores exploratorios
    -EF del ECOG de 0 o 1
    -Esperanza de vida ≥ 12 semanas
    -Pacientes que estén recibiendo anticoagulación terapéutica: tratamiento anticoagulante estable.
    -Prueba de VIH negativa en la selección.
    -Prueba de antígeno de superficie del virus de la hepatitis B (HBsAg) negativa en la selección.
    -Prueba de anticuerpos contra el antígeno central del virus de la hepatitis B (HBcAb) total negativa en la selección o prueba de HBcAb total positiva, seguida de un análisis del ADN del virus de la hepatitis B (VHB) negativo en la selección.
    -Prueba de anticuerpos contra el virus de la hepatitis C (VHC) negativa en la selección o bien prueba positiva seguida de un análisis negativo del ARN del VHC en la selección.
    -Mujeres en edad fértil: compromiso de practicar la abstinencia (de relaciones heterosexuales) o de utilizar métodos anticonceptivos con un índice de fallos < 1% anual durante el período de tratamiento y durante cinco meses después de la última dosis del tratamiento del estudio.
    E.4Principal exclusion criteria
    - Patients who have received surgery alone as definitive local therapy
    - HPV-negative patients who have a T1/T2 or N0/N1 tumor
    - HPV-positive oropharyngeal carcinoma patients who have a clinical N0/N1/N2 or pathological N0/N1 nodal stage
    - Patients, other than laryngeal cancer patients, who have persistent disease at the primary site and require salvage resection of primary tumor post chemoradiotherapy
    - Squamous cell carcinoma of the nasopharynx
    - Evidence of disease progression or metastatic disease during or following definitive local therapy documented in the 10- to 12-week post-definitive local therapy scans
    - Uncontrolled or symptomatic hypercalcemia
    - Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis
    - History of idiopathic pulmonary fibrosis, organizing pneumonia drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
    - Active tuberculosis
    - Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
    - Major surgical procedure, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
    - History of malignancy other than SCCHN within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ,or Stage I uterine cancer
    - Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
    - Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
    - Prior allogeneic stem cell or solid organ transplantation
    - Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
    - Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the last dose of atezolizumab
    - Current treatment with anti-viral therapy for HBV
    - Prior neoadjuvant treatment or any systemic anti-cancer therapy without definitive local therapy for locally advanced head and neck cancer
    - Treatment with investigational therapy within 28 days prior to initiation of study treatment
    - Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
    - Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug prior to initiation of study treatment
    -Treatment with systemic immunosuppressive within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
    - History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
    - Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
    - Pregnancy or breastfeeding, or intention of becoming pregnant during study treatment or within 5 months after the last dose of study treatment
    -Pacientes que hayan recibido solo cirugía como tratamiento local definitivo.
    -Pacientes VPH-negativos que tengan un tumor T1/T2 o N0/N1.
    -Pacientes VPH-positivos con carcinoma orofaríngeo que tengan un estadio ganglionar clínico de N0/N1/N2 o patológico de N0/N1.
    -Pacientes, aparte de los que tengan cáncer laríngeo, que presenten enfermedad persistente en el foco primario y requieran resección de rescate del tumor primario después de la QRT.
    -Carcinoma de células escamosas de la nasofaringe.
    -Signos de progresión de la enfermedad o metástasis durante o después del tratamiento local definitivo, documentados en las imágenes obtenidas 10-12 semanas después de dicho tratamiento local definitivo.
    -Hipercalcemia no controlada o sintomática
    -Antecedentes o presencia activa de enfermedades autoinmunitarias o inmunodeficiencias, incluidas entre otras miastenia grave, miositis, hepatitis autoinmunitaria, lupus eritematoso sistémico, artritis reumatoide, enfermedad inflamatoria intestinal, síndrome antifosfolipídico, granulomatosis de Wegener, síndrome de Sjögren, síndrome de Guillain-Barré y esclerosis múltiple
    -Antecedentes de fibrosis pulmonar idiopática, neumonía organizada , neumonitis medicamentosa, neumonitis idiopática o signos de neumonitis activa en la TC de tórax de selección.
    -Tuberculosis activa.
    -Enfermedad cardiovascular importante infarto de miocardio o accidente en los 3 meses previos al comienzo del tratamiento del estudio, arritmia inestable o angina inestable.
    -Intervención de cirugía mayor, excepto si se practica con fines diagnósticos, en las 4 semanas previas al comienzo del tratamiento del estudio o que previsiblemente vaya a ser necesaria en el transcurso del estudio.
    -Antecedentes de neoplasias malignas distintas del CCECC en los 5 años previos a la selección, exceptuando aquellas con un riesgo insignificante de metástasis o muerte como son el carcinoma in situ de cuello uterino, el carcinoma de piel distinto del melanoma, el cáncer de próstata localizado, el carcinoma ductal in situ o el cáncer de útero en estadio I tratados adecuadamente.
    Infección grave en las 4 semanas previas al comienzo del tratamiento del estudio, entre ellas, hospitalización por complicaciones de una infección, bacteriemia o neumonía grave.
    -Tratamiento con antibióticos terapéuticos por vía oral o IV en las 2 semanas previas al comienzo del tratamiento del estudio.
    -Alotrasplante de células madre o trasplante de órgano sólido previo.
    -Cualquier otra enfermedad, disfunción metabólica, signo en la exploración física o resultado analítico que contraindique el uso de un fármaco experimental, pueda afectar a la interpretación de los resultados o suponga un riesgo elevado de sufrir complicaciones del tratamiento para los pacientes.
    -Tratamiento con una vacuna de microorganismos vivos atenuados en las 4 semanas previas al comienzo del tratamiento del estudio o previsión de que se vaya a necesitar una vacuna de este tipo durante el tratamiento con atezolizumab o en los 5 meses posteriores a la última dosis de atezolizumab.
    -Tratamiento actual con antivirales para el VHB.
    -Uso previo de tratamiento neoadyuvante o cualquier tratamiento oncológico sistémico sin tratamiento local definitivo para un cáncer de cabeza y cuello localmente avanzado.
    -Uso de un tratamiento experimental en los 28 días previos al comienzo del tratamiento del estudio.
    -Tratamiento previo con agonistas de CD137 o tratamientos de bloqueo de puntos de control inmunitarios como anticuerpos terapéuticos anti-CTLA-4, anti-PD1 o anti-PDL1.
    -Tratamiento con inmunoestimuladores sistémicos en las 4 semanas, o el equivalente a 5 semividas del fármaco, previas al inicio del tratamiento del estudio, lo que suponga más tiempo.
    -Tratamiento con inmunodepresores sistémicos en las 2 semanas previas al comienzo del tratamiento del estudio o previsión de que vayan a necesitarse durante el transcurso del estudio
    -Antecedentes de reacciones alérgicas o anafilácticas graves a anticuerpos quiméricos o humanizados o a proteínas de fusión.
    -Hipersensibilidad documentada a productos elaborados con células de ovario de hámster chino o a cualquiera de los componentes de la formulación de atezolizumab
    -Embarazo, lactancia o intención de quedarse embarazada durante el tratamiento del estudio o en los 5 meses siguientes a la última dosis del tratamiento del estudio
    E.5 End points
    E.5.1Primary end point(s)
    1. IRF-assessed EFS
    2. OS after randomization
    1. SLE evaluada por CRI
    2. SG después de randomizacion
    E.5.1.1Timepoint(s) of evaluation of this end point
    1-2. Approximately up to 84 months
    1-2 Approximadamente hasta un máximo de 84 semanas
    E.5.2Secondary end point(s)
    1. Investigator-assessed EFS
    2. IRF-assessed EFS and investigator-assessed EFS at 1 and 2 years
    3. OS at 1, 2, and 3 years
    4. Change from baseline in physical functioning over time while receiving treatment as assessed through use of the five-item Physical Functioning subscale (Questions 15) of the European Organisation for Research and Treatment of Cancer Quality-of-Life-Core- 30 Questionnaire (EORTC QLQ-C30)
    5. Change from baseline in HRQoL over time while receiving treatment as assessed through use of the
    two-item Global health status/HRQoL subscale (Questions 29 and 30) of the EORTC QLQ-C30
    6. Incidence and severity of adverse events, including serious adverse events and immune-related adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.0
    7. Serum concentration of atezolizumab at specified timepoints
    8. Incidence of ADA response to atezolizumab
    1. SLE evaluada por investigador
    2. SLE evaluada por CRI e investigador al año y los dos años
    3. SG al año, dos años y tres años
    4. Variación de la función física con respecto al momento basal durante el tratamiento a lo largo del tiempo, evaluado mediante la subescala de función física de cinco apartados (preguntas 1-5) del cuestionario QLQ-C30 de la EORTC.
    5. Variación de la Calidad de Vida Relacionada con la Salud (CdVRS) con respecto al momento basal durante el tratamiento a lo largo del tiempo, evaluada mediante la subescala ESG/CdVRS de dos apartados (preguntas 29 y 30) del cuestionario QLQ-C30 de la EORTC.
    6. Incidencia e intensidad de los acontecimientos adversos, incluidos los acontecimientos adversos graves y los acontecimientos adversos de tipo inmunitario; la intensidad se determinará conforme a los CTCAE del NCI, v4.0.
    7. Concentración sérica de atezolizumab en los momentos especificados.
    8. Incidencia de la respuesta de ACF contra atezolizumab.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Approximately up to 84 months
    2. At 1 and 2 years
    3. At 1, 2, and 3 years
    4-6. Approximately up to 84 months
    7-8. Day 1 of Cycle 1, 2, 4, 8, 16 and at treatment discontinuation visit
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic 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 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 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 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 concerned6
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA34
    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
    Brazil
    Canada
    China
    France
    Germany
    India
    Italy
    Korea, Republic of
    Poland
    Russian Federation
    South Africa
    Spain
    Taiwan
    Ukraine
    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 end of this study is defined as the date when all patients meet one of the following criteria: experienced an OS event, become lost to follow-up, withdrawn consent, or completed at least 60 months of follow-up after randomization, whichever occurs first. In addition, the Sponsor
    may decide to terminate the study at any time.
    El final de este estudio se define como la fecha en la que todos los pacientes cumplan uno de los criterios siguientes: hayan experimentado un episodio de SG, sean pérdidas de seguimiento, hayan retirado el consentimiento o hayan completado al menos 60 meses de seguimiento tras la aleatorización, lo que suceda antes. Además, el promotor podrá decidir cancelar el estudio en cualquier momento.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months0
    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: 320
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 80
    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 Yes
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state18
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 104
    F.4.2.2In the whole clinical trial 400
    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)
    When appropriate, the Sponsor will offer access to atezolizumab to patients still benefiting from the treatment at the end of the study in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product. http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
    Cuando sea apropiado, el promotor ofrecerá acceso al atezolizumab a pacientes todavía beneficiándose del tratamiento al final del estudio de acuerdo con la Politica Global de Roche de acceso continuado a medicamentos en investigación
    http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
    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 Decision2018-03-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-02-23
    P. End of Trial
    P.End of Trial StatusOngoing
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
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