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    Summary
    EudraCT Number:2015-001112-35
    Sponsor's Protocol Code Number:010463QM
    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:2016-02-17
    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 number2015-001112-35
    A.3Full title of the trial
    A phase II study investigating preoperative MPDL3280A in operable transitional cell carcinoma of the bladder
    Estudio Fase II con MPDL3280A preoperatorio en carcinoma operable de células transicionales de vejiga (ABACUS)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A phase II study investigating use of the drug MPDL3280A before surgery in bladder cancer patients
    Estudio Fase II para investigar el fármaco MPDL3280A antes de cirugía en pacientes con cáncer de vejiga
    A.3.2Name or abbreviated title of the trial where available
    ABACUS
    A.4.1Sponsor's protocol code number010463QM
    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 SponsorQueen Mary University of London
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportF. Hoffmann-La Roche
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAPICES
    B.5.2Functional name of contact pointClinical Operations Department
    B.5.3 Address:
    B.5.3.1Street AddressAv. Antonio López, 16 - 1ºA
    B.5.3.2Town/ cityPinto (MADRID)
    B.5.3.3Post code28320
    B.5.3.4CountrySpain
    B.5.4Telephone number+34918166804
    B.5.5Fax number+34918169172
    B.5.6E-mailjuanluis.sanz@apices.es
    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 nameMPDL3280A
    D.3.2Product code RO5541267
    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 INNMPDL3280A
    D.3.9.3Other descriptive nameRO5541267
    D.3.9.4EV Substance CodeAS1
    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 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
    T2-T4N0M0 transitional cell carcinoma of the bladder
    Carcinoma de células transicionales de vejiga T2-T4N0M0
    E.1.1.1Medical condition in easily understood language
    Bladder cancer
    Cáncer de vejiga
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level PT
    E.1.2Classification code 10066752
    E.1.2Term Bladder transitional cell carcinoma stage IV
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level PT
    E.1.2Classification code 10066754
    E.1.2Term Bladder transitional cell carcinoma stage III
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level PT
    E.1.2Classification code 10066753
    E.1.2Term Bladder transitional cell carcinoma stage II
    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 MPDL3280A's ability to reduce the size of bladder cancer before surgery (measured as pathological complete response rate), and assess the impact of the drug on the body's immune system.
    Determinar la capacidad de MPDL3280A para reducir el tamaño del cáncer de vejiga antes de la cirugía (medida como la tasa de respuesta patológica completa), y evaluar el impacto del fármaco sobre el sistema inmune.
    E.2.2Secondary objectives of the trial
    The secondary objectives are as follows:
    - Assess the safety and tolerability of MPDL3280A in this patient population by collecting information about adverse events and surgical complications.
    - Assess the anti-tumour effect of MPDL3280A by examining the radiological response (looking at pre- and post-treatment MRI/CT scan images) and ?disease free survival? rates.
    - Assess the effect of MPDL3280A on overall patient survival.
    Los objetivos secundarios son los siguientes:
    - Evaluar la seguridad y tolerabilidad de MPDL3280A en esta población de pacientes mediante la recogida de información sobre los eventos adversos y las complicaciones quirúrgicas.
    - Evaluar el efecto antitumoral de MPDL3280A mediante la respuesta radiológica (evaluando las pruebas de imagen pre- y post- tratamiento) y la tasa de supervivencia libre de enfermedad.
    - Evaluar el efecto de MPDL3280A sobre la supervivencia global del paciente.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -Willing and able to provide written informed consent
    -Ability to comply with the protocol
    -Age ? 18 years
    -Histopathologically confirmed transitional cell carcinoma (T2-T4a) of the bladder. Patients with mixed histologies are required to have a dominant transitional cell pattern.
    -Residual disease after TURBT (surgical opinion, cystoscopy or radiological presence).
    -Fit and planned for cystectomy (according to local guidelines).
    -N0 or M0 disease CT or MRI (within 4 weeks of registration)
    -Representative formalin-fixed paraffin embedded (FFPE) bladder tumour samples with an associated pathology report that are determined to be available and sufficient for central testing.
    -Patients who refuse neoadjuvant cisplatin based chemotherapy or in whom neoadjuvant cisplatin based therapy is not appropriate.
    -Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
    -Negative pregnancy test within 2 weeks of Day 1 Cycle 1 for female patients of childbearing potential.
    -For female patients of childbearing potential to use a highly effecting form(s) of contraception (i.e. one that results in a low failure rate [<1% per year] when used consistently and correctly) and to continue its use for 90 days after the last dose of MPDL3280A.
    -Adequate hematologic and end-organ function within 4 weeks prior to the first study treatment defined by the following:
    a) ANC ? 1500 cells/?L (without granulocyte colony-stimulating factor support within 2 weeks prior to Cycle 1, Day 1)
    b) WBC counts > 2500/?L
    c)Lymphocyte count ? 500/?L
    d) Platelet count ? 100,000/?L (without transfusion within 2 weeks prior to Cycle 1, Day 1)
    e) Haemoglobin ? 9.0 g/dL (patients may be transfused or receive erythropoietic treatment to meet this criterion).
    f) AST or ALT, and alkaline phosphatase ? 2.5 times the institutional upper limit of normal (ULN) (patients with known Gilbert disease who have serum bilirubin level ? 3 × the institutional ULN may be enrolled).
    g) INR and aPTT ? 1.5 × the institutional ULN. This applies only to patients who are not receiving therapeutic anticoagulation; patients receiving therapeutic anticoagulation should be on a stable dose.
    h) Calculated creatinine clearance ? 20 mL/min (Cockcroft-Gault formula)
    1. Disposición y capacidad para dar el consentimiento informado por escrito.
    2. Capacidad para cumplir con el protocolo.
    3. Edad >= 18 años.
    4. Carcinoma de células transicionales de la vejiga (T2-T4a) confirmado histopatológicamente. Los pacientes con histologías mixtas deben presentar un patrón de células transicionales dominante.
    5. Enfermedad residual después de RTUTV (dictamen quirúrgico, cistoscopia o presencia radiológica).
    6. Pacientes en buen estado físico y en los que esté programada la realización de una cistectomía (de acuerdo con las directrices locales).
    7. Enfermedad en estadio N0 o M0 según TAC o RMN (en las 4 semanas siguientes al registro).
    8. Muestras tumorales de la vejiga fijadas en formol e incluidas en parafina (FFIP) representativas con un informe anatomopatológico asociado que estén disponibles y sean suficientes para el análisis central.
    9. Los pacientes que rechacen la quimioterapia neoadyuvante basada en el cisplatino o en los que el tratamiento neoadyuvante basado en cisplatino no sea adecuado.
    10. Estado funcional según la escala ECOG (Eastern Cooperative Oncology Group) de 0 o 1.
    11. Prueba de embarazo negativa en las 2 semanas previas al día 1 del ciclo 1 en mujeres con capacidad reproductora.
    12. Las mujeres con capacidad reproductora deben usar un método anticonceptivo muy eficaz (es decir, un método con una tasa de fracaso bajo [< 1 % al año] cuando se use de forma constante y correcta) y continuar con su uso durante 90 días tras la última dosis de MPDL3280A.
    13. Función hematológica y de órganos específicos aceptable en las 4 semanas previas a la primera administración del tratamiento del estudio, definida mediante los siguientes parámetros:
    a. Neutrófilos >= 1500 células/?l (sin administración de factor estimulante de colonias de granulocitos en las 2 semanas previas al ciclo 1, día 1)
    b. Leucocitos > 2500/?l
    c. Linfocitos >= 500/?l
    d. Plaquetas >= 100 000/?l (sin transfusión en las 2 semanas previas al día 1 del ciclo 1)
    e. Hemoglobina >= 9,0 g/dl (los pacientes podrán recibir transfusiones o tratamiento eritropoyético para cumplir este criterio).
    f. AST o ALT, y fosfatasa alcalina <= 2,5 veces el límite superior de la normalidad (LSN) del centro (se podrá incluir a pacientes con síndrome de Gilbert diagnosticado con un nivel de bilirrubina sérica ? 3 veces el LSN del centro).
    g. INR y TTPa <= 1,5 veces el LSN del centro. Esto solo se aplica a pacientes que no reciban anticoagulación terapéutica; los pacientes que reciban anticoagulación terapéutica deben mantener una dosis estable.
    h. Aclaramiento de creatinina calculado >= 20 ml/min (fórmula de Cockcroft-Gault).
    E.4Principal exclusion criteria
    -Pregnant and lactating female patients
    -Major surgical procedure within 4 weeks prior to enrolment or anticipation of need for a major surgical procedure during the course of the study other than for diagnosis
    -Previous intravenous chemotherapy for bladder cancer
    -Patients with prior allogeneic stem cell or solid organ transplantation
    -Prior treatment with CD137 agonists, anti-CTLA-4, anti?programmed death?1 (PD-1), or anti?PD-L1 therapeutic antibody or pathway-targeting agents
    -Patients must not have had oral/IV steroids for 14 days prior to study entry. The use of inhaled corticosteroids, physiologic replacement doses of glucocorticoids and mineralocorticoids is allowed.
    -Received therapeutic oral or intravenous antibiotics within 2 weeks prior to enrolment. Patients receiving prophylactic antibiotics (e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease) are eligible
    -Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study
    -Treatment with systemic immunostimulatory agents (e.g. interferons or interleukin [IL]?2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment
    -Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrolment
    -Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease (such as cirrhosis, uncontrolled major seizure disorder, or superior vena cava syndrome)
    -Malignancies other than UBC within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ? 3 + 4 and PSA < 10 ng/mL undergoing active surveillance and treatment naive)
    -Severe infections within 4 weeks prior to enrolment in the study (e.g. hospitalization for complications of infection, bacteraemia, severe pneumonia)
    -Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to enrolment, unstable arrhythmias, or unstable angina
    -History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted)
    -Patients with uncontrolled Type 1 diabetes . Patients with Type 1 diabetes controlled on a stable insulin regimen are eligible.
    -Patients with active hepatitis infection (positive hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (negative HBsAg test and a positive antibody to hepatitis B core antigen [anti-HBc] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA
    -Positive test for HIV
    -Patients with active tuberculosis
    -History of gastrointestinal disorders (medical or extensive surgery) which may interfere with the absorption of the study drug
    -Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or Ca > 12 mg/dL or corrected serum calcium > the institutional ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. Patients who are receiving bisphosphonate therapy or denosumab to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. Patients receiving denosumab prior to enrollment must be willing and eligible to receive bisphosphonate instead while on study
    -History of autoimmune disease including myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener?s granulomatosis, Sjögren?s syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, glomerulonephritis
    -Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone
    -History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    -Hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the MPDL3280A formulation
    1. Mujeres embarazadas o en periodo de lactancia.
    2. Intervención de cirugía mayor en las 4 semanas previas a la inclusión o preverse que será necesaria una intervención de cirugía mayor durante el transcurso del estudio.
    3. Haber recibido anteriormente quimioterapia por vía intravenosa para el cáncer de vejiga.
    4. Pacientes que hayan recibido un trasplante alogénico de células madre o de vísceras macizas.
    5. Tratamiento previo con agonistas frente a CD137; o anticuerpos terapéuticos anti-CTLA-4, anti-PD-1 (muerte celular programada) o anti-PD-L1; o fármacos dirigidos a rutas específicas.
    6. Los pacientes no deben haber recibido corticosteroides por vía oral o intravenosa durante los 14 días previos a la inclusión en el estudio. Se permite el uso de corticosteroides inhalados, dosis de reemplazo fisiológico de glucocorticoides y mineralocorticoides.
    7. Haber recibido tratamiento terapéutico con antibióticos por vía oral o i.v. en los 14 días previos a la inclusión (se permite tratamiento profiláctico con antibióticos [p. ej., para la prevención de una infección urinaria o de enfermedad pulmonar obstructiva crónica]).
    8. Administración de una vacuna atenuada elaborada con microbios vivos en las 4 semanas anteriores a la inclusión o previsión de que deberá administrarse una vacuna de este tipo durante el estudio.
    9. Tratamiento con fármacos inmunoestimuladores sistémicos (incluidos interferones o interleucina [IL]-2) en las 4 semanas anteriores a la inclusión o en un periodo de cinco semividas del fármaco (lo que sea menor).
    10. Tratamiento con cualquier otro medicamento en investigación o participación en otro ensayo clínico con intención terapéutica en las 4 semanas anteriores a la inclusión.
    11. Signos de enfermedad concomitante no controlada significativa que pudiera afectar al cumplimiento del protocolo o a la interpretación de los resultados, como hepatopatía significativa (p. ej., cirrosis, trastorno convulsivo mayor no controlado o síndrome de la vena cava superior).
    12. Neoplasias malignas, aparte de CVU, en los 5 años anteriores al día 1 del ciclo 1, a excepción de los que tengan un riesgo no significativo de metástasis o muerte y sean tratados con intención curativa (como carcinoma in situ de cuello uterino tratado, cáncer de piel de células basales o escamosas, o carcinoma ductal in situ tratado quirúrgicamente con intención curativa) o cáncer de próstata localizado tratado con intención curativa y ausencia de recidiva del antígeno prostático específico (PSA) o cáncer incidental de próstata (escala de Gleason ? 3 + 4 y PSA < 10 ng/ml sometidos a seguimiento activo y que no hayan recibido tratamiento previo).
    13. Infecciones graves en las 4 semanas anteriores a la inclusión en el estudio.
    14. Enfermedad cardiovascular significativa, como cardiopatía NYHA II o superior, infarto de miocardio en los 3 meses anteriores a la inclusión, arritmias inestables o angina de pecho inestable.
    15. Antecedentes de fibrosis pulmonar idiopática (incluida neumonitis), neumonitis inducida por fármacos, neumonía organizada (es decir, bronquiolitis obliterante, neumonía organizada criptogénica) o signos de neumonitis activa en la TAC torácica de la selección (se permiten antecedentes de neumonitis por radiación en el campo de irradiación [fibrosis]).
    16. Pacientes con diabetes mellitus de tipo 1 no controlada.
    17. Pacientes con hepatitis activa (definida como la presencia positividad en la prueba de detección del antígeno de superficie de la hepatitis B [HBsAg] en la selección) o con hepatitis C.
    18. Resultado positivo en la prueba de detección del VIH.
    19. Pacientes con tuberculosis activa.
    20. Antecedentes de trastornos gastrointestinales (trastornos médicos o cirugía extensa) que puedan interferir en la absorción del fármaco del estudio.
    21. Hipercalcemia no controlada (> 1,5 mmol/l de calcio ionizado o Ca > 12 mg/dl o calcio sérico corregido > LSN del centro) o hipercalcemia sintomática que requiera tratamiento ininterrumpido con bisfosfonatos o denosumab.
    22. Antecedentes de enfermedad autoinmunitaria, incluidas, entre otras, miastenia gravis, miositis, hepatitis autoinmunitaria, lupus eritematoso sistémico, artritis reumatoide, enfermedad inflamatoria intestinal, trombosis vascular asociada a síndrome antifosfolípido, granulomatosis de Wegener, síndrome de Sjögren, síndrome de Guillain-Barré, esclerosis múltiple, vasculitis o glomerulonefritis.
    23. Pacientes con antecedentes de hipotiroidismo de naturaleza autoinmunitaria, a menos que estén siendo tratados con una dosis estable de hormonoterapia de reemplazo de hormonas tiroideas.
    24. Antecedentes de reacciones alérgicas graves, anafilácticas u otras reacciones de hipersensibilidad a anticuerpos quiméricos o humanizados o a proteínas de fusión.
    25. Hipersensibilidad o alergia conocida a productos biofarmacéuticos producidos en células de ovario de hámster chino o a cualquier componente de la formulación de MPDL3280A.
    E.5 End points
    E.5.1Primary end point(s)
    Clinical: Pathological complete response rate (pCRR) defined as ?20% decrease in residual disease of the bladder, based on histological evaluation of the resected bladder specimen collected during cystectomy (post-treatment).

    Biological: Dynamic changes in T cell subpopulations (CD8 and/or CD3) measured in tumour samples collected pre- and post-treatment with MPDL3280A.
    Clínico: Tasa de respuesta completa anatomopatológica definida como una reducción ? 20 % de la enfermedad residual de la vejiga basada en la evaluación histológica de una muestra de la vejiga reseccionada obtenida durante la cistectomía (después del tratamiento).

    Biológico: Cambios dinámicos en las subpoblaciones de linfocitos T (CD8 y/o CD3) medidos en muestras tumorales obtenidas antes y después del tratamiento con MPDL3280A.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Clinical: pCR rate will be based on histological evaluation of the resected bladder specimen collected during cystectomy (after 1-2 cycles of MPDL3280A treatment).

    Biological: The change in T cell expression will be measured in tumour biopsy samples collected before and after treatment with MPDL3280A (an archival sample and a sample taken at cystectomy or post- treatment biopsy).
    Clínico: tasa de pCR se basará en la evaluación histológica de la muestra de la vejiga resecada recogida durante la cistectomía (después de 1-2 ciclos de tratamiento con MPDL3280A).

    Biológico: El cambio en la expresión de las células T se mide en muestras de biopsias tumorales recogidas antes y después del tratamiento con MPDL3280A (una muestra de archivo y una muestra tomada en la cistectomía o biopsia post-tratamiento).
    E.5.2Secondary end point(s)
    - Incidence, nature and severity of adverse events graded according to NCI-CTCAE v4.03 collected during and after MPDL3280A treatment.
    - Surgical complications as assessed by the Clavien-Dindo scoring system.
    - Radiological response, defined as a >30% decrease in tumour diameter from the baseline scan based on local investigator assessments
    - Disease-free survival, defined as time between the date of enrolment to first evidence of disease progression based on local investigator assessments or death, whichever occurs first.
    - Overall survival, defined as the time between the date of enrolment and death due to any cause.
    - Incidencia, naturaleza e intensidad de los acontecimientos adversos, clasificados según los CTCAE del NCI, v4.03, y notificados durante el tratamiento con MPDL3280A.
    - Complicaciones quirúrgicas según la evaluación del sistema de clasificación de Clavien-Dindo.
    - Respuesta radiológica, definida como una disminución del diámetro tumoral > 30 % respecto a las imágenes basales según evaluación del investigador.
    - Supervivencia libre de enfermedad, definida como el tiempo transcurrido entre la fecha de inclusión del paciente y la aparición de los primeros signos de progresión de la enfermedad según las evaluaciones locales del investigador o la muerte del paciente, lo que suceda primero.
    - Supervivencia global, definida como el tiempo transcurrido entre la fecha de inclusión del paciente y su muerte por cualquier causa.
    E.5.2.1Timepoint(s) of evaluation of this end point
    - Adverse events will be recorded during treatment and up to 24 weeks post cystectomy (AEs are recorded up to 4 weeks post-cystectomy, and unresolved AEs monitored until resolved or until 24 weeks post-cystectomy). Surgical complications will be assessed by the Clavien-Dindo scoring system post-cystectomy.
    - Radiological response will be assessed before and after treatment with MPDL3280A (baseline and pre-cystectomy).
    - Disease free survival will be recorded from enrolment until first evidence of disease recurrence or death; patients are followed up for 2 years after cystectomy.
    - Overall survival is defined as time from enrolment to death due to any cause. Patients are followed for 2 years after cystectomy; data will be collected until this time point.
    - Los acontecimientos adversos (AAs) se registran durante el tratamiento y hasta 24 semanas después de la cistectomía (los AAs se registran hasta 4 semanas después de la cistectomía, y los AAs no resueltos se monitorizarán hasta que remitan o hasta 24 semanas después de la cistectomía). Las complicaciones quirúrgicas serán evaluadas por el sistema de puntuación Clavien-Dindo post-cistectomía.
    - La Respuesta Radiológica será evaluada antes y después del tratamiento con MPDL3280A
    - La supervivencia libre de enfermedad se evaluará desde la inclusión hasta la primera evidencia de recaida de la enfermedad o la muerte.
    - La supervivencia global se define como el tiempo desde la inclusión hasta la muerte. Los pacientes son seguidos durante 2 años después de la cistectomía.
    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) 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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    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 No
    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.8.2.4Number of treatment arms in the trial1
    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 concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA28
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months3
    E.8.9.2In all countries concerned by the trial days1
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.4.1Number of subjects for this age range: 0
    F.1.1.5Children (2-11years) No
    F.1.1.5.1Number of subjects for this age range: 0
    F.1.1.6Adolescents (12-17 years) No
    F.1.1.6.1Number of subjects for this age range: 0
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 55
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 30
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 85
    F.4.2.2In the whole clinical trial 85
    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)
    None, this is a window of opportunity trial. On completion of the study, participating patients will be considered for further treatment at the discretion of the treating physician. MPDL3280A is still in development and is not available outside the clinical trial setting.
    Ninguno, este es un ensayo "window of opportunity". Al finalizar el estudio, los pacientes participantes serán considerados para tratamiento adicional según el criterio del investigador. El fármaco MPDL3280A está todavía en desarrollo y no está disponible fuera del contexto del ensayo clínico.
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-02-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-02-10
    P. End of Trial
    P.End of Trial StatusOngoing
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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