Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   39572   clinical trials with a EudraCT protocol, of which   6487   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2019-000782-21
    Sponsor's Protocol Code Number:VHIO19001
    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:2019-04-30
    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 number2019-000782-21
    A.3Full title of the trial
    Phase II Study of Avelumab plus chemotherapy in the peri-operative treatment for patients with resectable Gastric cancer (GC) or Gastroesophageal Junction cancer (GEJC) – MONEO Study
    Estudio fase II de Avelumab más quimioterapia en el tratamiento perioperatorio de pacientes con carcinoma gástrico (CG) o de la unión gastroesofágica (CUGE) localmente avanzado resecable - Estudio MONEO
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase II Study of Avelumab plus chemotherapy in the peri-operative treatment for patients with resectable Gastric cancer (GC) or Gastroesophageal Junction cancer (GEJC) – MONEO Study
    Estudio fase II de Avelumab más quimioterapia en el tratamiento perioperatorio de pacientes con carcinoma gástrico (CG) o de la unión gastroesofágica (CUGE) localmente avanzado resecable - Estudio MONEO
    A.3.2Name or abbreviated title of the trial where available
    MONEO
    MONEO
    A.4.1Sponsor's protocol code numberVHIO19001
    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 SponsorVall d' Hebron Institute of Oncology (VHIO)
    B.1.3.4CountrySpain
    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 supportMerck, S.L.
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationVall d' Hebron Institute of Oncology (VHIO)
    B.5.2Functional name of contact pointCRS Unit (VHIO)
    B.5.3 Address:
    B.5.3.1Street AddressCentro Cellex, Calle Natzaret, 115-117
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08035
    B.5.3.4CountrySpain
    B.5.4Telephone number349348930006502
    B.5.5Fax number34934894212
    B.5.6E-mailsmunoz@vhio.net
    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 nameAvelumab
    D.3.2Product code MSB0010718C
    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 INNAVELUMAB
    D.3.9.3Other descriptive nameAvelumab
    D.3.9.4EV Substance CodeSUB180078
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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) Yes
    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
    Resectable Gastric cancer (GC) or Gastroesphageal Junction cancer (GEJC)
    Carcinoma gástrico (CG) o de la unión gastroesofágica (CUGE) localmente avanzado resecable
    E.1.1.1Medical condition in easily understood language
    Resectable Gastric cancer (GC) or Gastroesphageal Junction cancer (GEJC)
    Carcinoma gástrico (CG) o de la unión gastroesofágica (CUGE) localmente avanzado resecable
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10017758
    E.1.2Term Gastric 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 investigate whether the addition of avelumab to FLOT chemotherapy (docetaxel, oxaliplatin and fluorouracil/leucovorin) improves efficacy in terms of pathological complete response (pCR) rate, in GC and GEJC patients compared to the historical data of chemotherapy alone in the neoadjuvant setting.
    Investigar si la incorporación de avelumab a la quimioterapia FLOT (docetaxel, oxaliplatino y fluorouracilo / leucovorina) neoadyuvante mejora la eficacia de dicha terapia con respecto al índice de respuesta patológica completa (RPc) en pacientes con CG y CUGE con respecto a los datos históricos de quimioterapia sin neoadyuvancia.
    E.2.2Secondary objectives of the trial
    - To evaluate the addition of avelumab to the perioperative chemotherapy in regard to the following:
    o Overall survival (OS)
    o Disease-free survival (DFS)
    o Progression-free survival (PFS)
    o Surgical resection rate (R0)
    o Overall Response Rate (ORR) to neoadjuvancy
    - To determine the safety and tolerability of avelumab with FLOT chemotherapy.
    - To perform a comprehensive analysis of biomarkers, as exploratory endpoints.
    - Evaluar los efectos de añadir avelumab a la quimioterapia perioperatoria sobre:
    o La supervivencia global (OS)
    o Supervivencia libre de enfermedad (DFS)
    o Supervivencia libre de progresión (PFS)
    o Índice de resección quirúrgica (R0)
    o Índice de respuesta global (ORR) a neoadyuvancia
    - Determinar la seguridad y tolerancia de avelumab añadido a quimioterapia FLOT.
    - Realizar un análisis exhaustivo de biomarcadores como criterios de valoración exploratorios.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Histologically proven, gastric or GEJ adenocarcinoma (Siewert I-III).
    2.Availability of a paraffin block from the diagnostic endoscopic biopsy (and a fresh biopsy if possible), and a second tumor block (fresh + paraffin) from the surgical specimen.
    3.Have evaluable disease as defined by RECIST 1.1 and determined by investigator assessment, with the absence of distant metastases on CT scan of thorax, abdomen and pelvis.
    4.Patient medically fit and amenable to gastrectomy/esophagectomy with curative intent as confirmed by a multidisciplinary team discussion.
    5.UICC tumor stage Ib (T1N1 only, T2N0 not eligible) to IIIC, as defined by CT, according to the 7th AJCC Edition.
    6.Age ≥ 18 years.
    7.WHO performance status 0-1.
    8.Adequate organ function (assessed within 7 days prior treatment initiation):
    a.White blood cell count (WBC) > 3 x 109 /L
    b.Absolute neutrophil count (ANC) > 1.5 x 109 /L
    c.Platelets ≥ 100 x 109 /L
    d.Estimated glomerular filtration rate should be > 50 ml/min
    e.Total bilirubin within normal limits (if the patient has documented Gilbert’s disease ≤ 1.5 x ULN or direct bilirubin ≤ ULN).
    f.Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 x ULN.
    9.In case of anticoagulation, investigator and patient should agree to replace any oral anticoagulation by subcutaneous administration of low-molecular weight heparin in equivalent doses before treatment start;
    10.For women who are not postmenopausal (> 12 months of non-therapy induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to remain abstinent or use single or combined contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 12 months after the last treatment dose
    11.For men: agreement to remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for at least 12 months after the last dose of study treatment. Abstinence is only acceptable if it is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods for contraception.
    12.For all female patients who are not confirmed postmenopausal (> 12 months of non-therapy induced amenorrhea) or surgically sterile (absence of ovaries and/or uterus) a negative serum pregnancy test (β-human chorionic gonadotropin [β-hCG]) result should be available before treatment and within 7 days from treatment start should be performed. Female patients should not be breast feeding.
    13.Written informed consent must be given according to ICH/GCP, and national/local regulations.
    1.Adenocarcinoma gástrico o CUGE histológicamente confirmado (Siewert I-III).
    2.Disponibilidad de un bloque fijado en parafina procedente de la biopsia diagnóstica endoscópica, y un segundo bloque del tumor (fresco + parafina) de la pieza quirúrgica.
    3.Padecer enfermedad evaluable, definida según los criterios RECIST v1.1 a criterio del investigador, con ausencia de metástasis a distancia confirmado por TAC de tórax, abdomen y pelvis.
    4.Paciente médicamente apto y susceptible de ser tratado mediante gastrectomía/esofagectomía con intención curativa confirmado en sesión multidisciplinar.
    5.Fase Ib a IIIC según UICC (solo T1N1, T2N0 no válidos), definida mediante TAC, de acuerdo con la 7a Edición de AJCC.
    6.Edad ≥ 18 años.
    7.Estado funcional 0-1 según los criterios de la OMS.
    8.Función orgánica normal (evaluada en los siete días anteriores al inicio del tratamiento).
    a.Recuento de glóbulos blancos (GB) > 3 x 109 /L
    b.Recuento absoluto de neutrófilos (ANC) > 1.5 x 109 /L
    c.Plaquetas ≥ 100 x 109 /L
    d.Tasa de filtración glomerular > 50 ml/min
    e.Bilirrubina total dentro de los límites normales (si el paciente padece la enfermedad de Gilbert ≤ 1.5 x ULN o bilirrubina directa ≤ ULN).
    f.Aspartato transaminasa (AST) y alanina transaminasa (ALT) ≤ 2.5 x ULN.
    9.En caso de anticoagulación, el investigador y el paciente deberán acordar sustituir los anticoagulantes orales por la administración subcutánea de heparina de bajo peso molecular en dosis equivalentes antes de iniciar el tratamiento;
    10.Para mujeres que no sean posmenopáusicas (> 12 meses de amenorrea no causada por terapia) o quirúrgicamente estériles (ausencia de ovarios y/o útero): compromiso de permanecer abstinente o de emplear uno o varios métodos anticonceptivos con un índice de fallo < 1% al año durante el periodo de tratamiento, y al menos en los 12 meses posteriores a la última dosis del tratamiento.
    11.Para los hombres: compromiso de permanecer abstinente o emplear el preservativo más otro método anticonceptivo adicional que, en su conjunto, resulten en un índice de fallo < 1% durante el periodo del tratamiento, y al menos en los 12 meses posteriores a la última dosis del tratamiento en estudio. Solo se considerará aceptable la abstinencia si se ajusta a las preferencias y estilo de vida habitual del paciente. La abstinencia periódica (e.j. método del calendario, ovulación, sintotérmico postovulatorio) y la marcha atrás no se considerarán métodos anticonceptivos aceptables.
    12.Antes de iniciar el tratamiento y en los siete días posteriores al inicio del mismo, a todas las pacientes que no sean posmenopáusicas (> 12 meses de amenorrea no provocada por medicación) o quirúrgicamente estériles (ausencia de ovarios y/o útero) se les realizará un test de embarazo en suero (β-gonadotropina coriónica humana) que deberá ser negativo. Las pacientes no podrán estar en periodo de lactancia.
    13.Se obtendrá el consentimiento informado de los pacientes según los criterios ICH/GCP y las leyes y regulaciones nacionales y locales.
    E.4Principal exclusion criteria
    1.Other histology different from adenocarcinoma.
    2.Has had previous therapy for gastric or GEJ cancer.
    3.Known hypersensitivity to the components of anti-PD-L1, docetaxel, oxaliplatin, fluorouracil/leucovorin.
    4.Known dihydropyrimidine dehydrogenase (DPD) deficiency.
    5.Previous malignancy within the last 5 years, except for adequately treated cervical carcinoma in situ, localized non-melanoma skin cancer, or other curatively treated cancer without impact on the patient’s overall prognosis according to the judgment of the investigator.
    6.Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those condition should be discussed with the patient before registration in the trial.
    7.History of clinically significant comorbidities.
    8.Patients medically unfit for FLOT chemotherapy, according to the local guidance.
    9.Active autoimmune disease that has required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxin, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
    10.Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Current use of immunosuppressive medication, EXCEPT for the following: a. intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection); b. Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent; c. Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). History or evidence of interstitial lung disease or active, non-infectious pneumonitis.
    11.Active infection requiring systemic therapy.
    12.Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected). Test for HBV and HCV are required for the screening.
    13.Received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu-vaccines and are allowed; however intranasal influenza vaccines are live attenuated vaccines, and are not allowed.
    14.Prior organ transplantation including allogenic stem-cell transplantation.
    15.Known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI-CTCAE v4.0 Grade ≥ 3).
    16.Persisting toxicity related to prior therapy (NCI-CTCAE v4.0 Grade > 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator’s judgment are acceptable.
    17.Other severe acute or chronic medical conditions including immune colitis, inflammatory bowel disease, immune pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behaviour; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
    18.Pregnant women and lactating females are excluded from this study.
    1.Cáncer histológicamente distinto al adenocarcinoma.
    2.Haber recibido anteriormente tratamiento para el cáncer gástrico o CUGE.
    3.Hipersensibilidad conocida a los componentes de anti-PD-L1, docetaxel, oxaliplatino, fluorouracilo / leucovorina.
    4.Déficit conocido de dihidropirimidina deshidrogenasa (DPD).
    5.Haber padecido una malignidad anterior en los cinco últimos 5 años, excepto el carcinoma in situ de cérvix adecuadamente tratado, el cáncer de piel no melanoma, u otros tipos de cáncer tratados curativamente sin efecto en el pronóstico global del paciente, a juicio del investigador.
    6.Padecer cualquier patología psicológica, familiar, sociológica o geográfica que potencialmente pudiera impedir el cumplimiento del protocolo y el plan de seguimiento. Antes de su inscripción en el ensayo, se les preguntará a los pacientes sobre las mismas.
    7.Historia de comorbilidades clínicamente significativas.
    8.Pacientes medicamente no aptos para recibir quimioterapia FLOT, según los criterios del centro.
    9.Padecer una enfermedad autoinmune activa que haya precisado tratamiento sistémico en los últimos dos años (por ejemplo, el uso de agentes modificadores de la enfermedad, corticosteroides o fármacos inmunosupresores). Las terapias de reemplazo (Tiroxina, insulina o terapia de reemplazo fisiológico de corticosteroides para la insuficiencia suprarrenal o hipofisaria) no se consideran tratamientos sistémicos. .
    10.Diagnóstico de inmunodeficiencia: estar recibiendo terapia esteroidea sistémica o cualquier otro tipo de terapia inmunosupresora en los siete días anteriores a la primera dosis del tratamiento en estudio. Estar tomando actualmente medicación inmunosupresora, EXCEPTO para lo siguiente> a. esteroides intranasales, inhalados, tópicos o inyecciones locales de esteroides (p.ej. inyecciones intraarticulares) - b. Corticosteroides sistémicos en dosis fisiológicas ≤ 10 mg/día de prednisona o equivalente. c. Esteroides como premeditación para reacciones de hipersensibilidad (p.ej. premeditación para TAC). Historia o prueba de enfermedad pulmonar intersticial o neumonitis no infecciosa activa.
    11.Infección activa que requiera terapia sistémica.
    12.Historia conocida de infección por el virus de inmunodeficiencia adquirida (VIH) (anticuerpos 1/2 VIH), hepatitis B activa (p.ej., HBsAg reactiva) o Hepatitis C (p.ej., se detecta RNA del VHC [cualitativo]). Sera necesario someterse a una prueba de VHB y VHC para el cribado.
    13.Haber recibido una vacuna viva en los 30 días anteriores a la fecha prevista de inicio de la terapia. Nota: Se permitirá la inyección de vacunas de la gripe estacional, ya que estas suelen ser vacunas inactivadas de la gripe. Sin embargo, no se admitirán las vacunas intranasales de la gripe, ya que son vacunas vivas atenuadas.
    14.Haber recibido un transplante de órgano, incluidos los trasplantes orogénicos.
    15.Hipersensibilidad severa conocida al producto en estudio o a alguno de los componentes de su fórmula, incluyendo las reacciones de hipersensibilidad severa a los anticuerpos monoclonales (NCI-CTCAE v4.0 Grado ≥ 3).
    16.Toxicidad persistente relacionada con terapias anteriores (NCI-CTCAE v4.0 Grado > 1). No obstante, se aceptaran la alopecia, la neuropatía sensorial grado ≤ 2 u otro grado ≤ 2 que, a juicio del investigador, no constituyan un riesgo de seguridad.
    17.Otros criterios de exclusió: padecer otras patologías médicas crónicas o agudas severas, incluyendo la colitis inmune, la enfermedad intestinal inflamatoria, la neumonitis inmune, la fibrosis pulmonar o las afecciones psiquiátricas, incluyendo la ideación o comportamiento suicida reciente (en el último año) o activo; o anomalías de laboratorio que pudieran aumentar el riesgo asociado a la participación en el estudio o a la administración del tratamiento en estudio, o que pudieran interferir en la interpretación de los resultados del estudio y que a juicio del investigador, hacen que el pacientes no sea apto para su inclusión en el estudio.
    18.Las embarazadas y mujeres en periodo de lactancia serán excluidas del estudio.
    E.5 End points
    E.5.1Primary end point(s)
    - Pathological complete response (pCR) rate, where pCR is defined as the absence of residual tumor based on evaluation of the resected esophagogastric specimen according to Becker remission criteria.
    - Índice de respuesta patológica completa (pCR), definida como la ausencia de tumor residual confirmada mediante la evaluación de muestras esofagogástricas extraídas, según los criterios de remisión de Becker.
    E.5.1.1Timepoint(s) of evaluation of this end point
    After the surgery
    Tras la cirugía
    E.5.2Secondary end point(s)
    Secondary Efficay endpoints:
    •Overall survival (OS) [time frame: from the initial date of neoadjuvant chemotherapy to the date of death due to any cause. Patients without documentation of death at the time of analysis will be censored at the last follow-up date]. Estimated using Kaplan-Meier method.
    •Disease-free survival (DFS) [time frame: from the surgery to the first observation of disease relapse or death due to any cause. Patients without an event prior to the time of analysis will be censored at the last relapse-free assessment]. Relapse is defined according to RECIST v1.1. Estimated using Kaplan-Meier method.
    •Progression-free survival (PFS) [time frame: from the initial date of neoadjuvant chemotherapy to the date of first documentation of disease progression or death due to any cause, whichever occurs first. Patients without an event prior to the time of analysis will be censored at the last assessment that is stable disease (SD) or better]. Progression is defined according to RECIST v1.1. Estimated using Kaplan-Meier method.
    •Surgical complete resection rate (R0). This is a complete macroscopic resection of the gross tumor with negative surgical margins.
    •Overall Response rate (ORR) to neoadjuvancy, as the proportion of subjects with complete response (CR)and partial response (PR), according to RECIST v1.1. [time frame: from the initial date of neoadjuvant chemotherapy to 3 years post-treatment).
    Safety endpoints: safety of the combination of avelumab with FLOT chemotherapy (docetaxel, oxaliplatin and fluorouracil/leucovorin)
    Exploratory Endpoints
    •Pathological immune response (pIR)
    •Characterization of the immune contexture
    •Immunodynamic follow-up
    •TCR clonality assessment
    Criterios secundarios de valoración de eficacia:
    •Supervivencia global (OS) [horizonte temporal: desde la fecha de inicio de la quimioterapia neoadyuvante hasta la fecha de fallecimiento por cualquier causa. Los pacientes cuyo fallecimiento no esté documentado en el momento del análisis serán censurados en la última fecha de seguimiento]. Cálculos realizados siguiendo el método de Kaplan-Meier.
    •Supervivencia libre de enfermedad (DFS) [horizonte temporal: desde la cirugía hasta la primera observación de recaída de la enfermedad o fallecimiento por cualquier causa. Los pacientes sin eventos anteriores al momento del análisis serán censurados en la última evaluación libre de recaída]. La recurrencia se definirá según los criterios RECIST v1.1. Los cálculos se realizarán siguiendo el método de Kaplan-Meier.
    •Supervivencia libre de enfermedad (PFS) [horizonte temporal: desde la fecha de inicio de la quimioterapia neoadyuvante hasta el primer registro documentado de progresión de la enfermedad o fallecimiento por cualquier caso, lo que primero ocurriera. Los pacientes sin eventos anteriores a la fecha de análisis serán censurados en la última visita en la que la enfermedad permanecía estable (SD) o había mejorado]. La progresión se definirá según los criterios RECIST v1.1. Los cálculos se realizarán según el método de Kaplan-Meier.
    •Índice de extracción quirúrgica completa (R0). Se define como la extracción macroscópica completa del tumor total con márgenes quirúrgicos negativos.
    •Índice de respuesta global (ORR) a neoadyuvancia, definido como la proporción de sujetos con respuesta completa (CR) y respuesta parcial (PR), según los criterios RECIST v1.1. [horizonte temporal: desde la fecha de inicio de la quimioterapia neoadyuvante hasta transcurridos tres años desde la finalización del tratamiento).
    Criterios de valoración de seguridad: seguridad de la combinación de avelumab con la quimioterapia FLOT (docetaxel, oxaliplatino y fluorouracilo / leucovorina).
    Criterios de valoración exploratorios
    •Respuesta inmune patológica (pIR)
    •Caracterización del contexto inmunológico
    •Seguimiento inmunodinámico
    •Evaluación de la clonalidad TCR
    E.5.2.1Timepoint(s) of evaluation of this end point
    -Secondary Efficay endpoints:
    •Overall survival (OS): Last follow-up date
    •Disease-free survival (DFS): Last relapse-free assessment
    •Progression-free survival (PFS):Date of first documentation of disease progression or death due to any cause, whichever occurs first
    •Surgical complete resection rate (R0): After surgery
    •Overall Response rate (ORR) to neoadjuvancy: 3 years post-treatment
    -safety endpoints: during all the trial
    -Exploratory Endpoints: after surgery, once all patients have been operated
    Criterios secundarios de valoración de eficacia:
    •Supervivencia global (OS): fecha de último seguimiento
    •Supervivencia libre de enfermedad (DFS): última evaluación sin recaída
    •Supervivencia libre de enfermedad (PFS): Fecha de la primera progresión de la enfermedad documentada o muerte debida a cualquier causa, lo que ocurra antes
    •Índice de extracción quirúrgica completa (R0): Tras la cirugía
    •Índice de respuesta global (ORR) a neoadyuvancia: 3 años post-tratamiento
    - Criterios de valoración de seguridad: durante todo el ensayo
    - Criterios de valoración exploratorios: tras la cirugía, cuando todos los pacientes hayan sido operados
    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 Yes
    E.6.13.1Other scope of the trial description
    Biomarkers
    Biomarcadores
    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 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 concerned12
    E.8.5The trial involves multiple Member States No
    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 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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months4
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months4
    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: 26
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 11
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    The informed consent has an special section to oral consent and also allows to consent a legal representative
    El consentimiento informado tiene una sección para consentir oralmente y también se permite consentir al representante legal
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state37
    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. Patients will follow standard of care
    Ninguno. Los pacientes seguirán la práctica clínica habitual
    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 Decision2019-06-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-06-21
    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
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA