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    Summary
    EudraCT Number:2015-001909-14
    Sponsor's Protocol Code Number:APL-B-021-13
    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:2016-02-03
    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 number2015-001909-14
    A.3Full title of the trial
    A Phase II Study of Plitidepsin in Patients with Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma.
    Estudio de fase II de plitidepsin en pacientes con linfoma angioinmunoblástico de células T en recaída o refractario.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase II Study of Plitidepsin in Patients with Angioimmunoblastic T-cell Lymphoma.
    Estudio de fase II de plitidepsin en pacientes con linfoma angioinmunoblástico de células T.
    A.4.1Sponsor's protocol code numberAPL-B-021-13
    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 SponsorPharma Mar, S.A.
    B.1.3.4CountrySpain
    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 supportPharma Mar, S.A.
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPharma Mar, S.A.
    B.5.2Functional name of contact pointClinical Trials
    B.5.3 Address:
    B.5.3.1Street AddressAvd. De Los Reyes, no 1 Pol. Ind. La Mina
    B.5.3.2Town/ cityColmenar Viejo (Madrid)
    B.5.3.3Post code28770
    B.5.3.4CountrySpain
    B.5.4Telephone number3491846 60 00
    B.5.5Fax number3491846 60 03
    B.5.6E-mailclinicaltrials@pharmamar.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 nameAplidin
    D.3.4Pharmaceutical form Powder and solvent for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNplitidepsin
    D.3.9.3Other descriptive namePLITIDEPSIN
    D.3.9.4EV Substance CodeSUB31204
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Relapsed or Refractory Angioimmunoblastic T-cell Lymphoma.
    Linfoma angioinmunoblástico de células T en recaída o refractario.
    E.1.1.1Medical condition in easily understood language
    Angioimmunoblastic T-cell Lymphoma.
    Linfoma angioinmunoblástico de células T.
    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 10002453
    E.1.2Term Angioimmunoblastic T-cell lymphoma refractory
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of plitidepsin on the basis of overall response rate (ORR) in patients with relapsing/refractory angioimmunoblastic T-cell lymphoma (AITL).
    Evaluar la eficacia de plitidepsin según la tasa de respuesta global (TRG) en pacientes con linfoma angioinmunobástico de linfocitos T (LAIT) en recaída/refractario.
    E.2.2Secondary objectives of the trial
    ?To evaluate other efficacy endpoints (time-to-event parameters:
    duration of response [DoR], progression-free survival [PFS], PFS at 6/12
    months [PFS6/PFS12], intrapatient PFS/TTP, overall survival [OS] and
    OS at 6/12 months [OS6/OS12]).
    ?To evaluate the safety profile of plitidepsin in this patient population.
    ?To characterize the pharmacokinetics (PK) of plitidepsin.
    ?To identify biomarkers that may be clinical endpoint surrogates for
    future plitidepsin studies or that may be predictive of plitidepsin activity.
    ?Evaluar otros criterios de valoración de la eficacia (parámetros del
    tiempo hasta el acontecimiento: duración de la respuesta [DDR],
    supervivencia libre de progresión [SLP], SLP a los 6/12 meses
    [SLP6/SLP12], SLP/TTP intrapaciente, supervivencia global [SG] y SG a
    los 6/12 meses [SG6/SG12]).
    ?Valorar el perfil de seguridad de plitidepsin en esta población de pacientes.
    ?Caracterizar la farmacocinética (FC) de plitidepsin.
    ?Identificar biomarcadores que se pueden considerar criterios de valoración clínica indirectos para futuros estudios de plitidepsin o que pueden pronosticar la actividad de plitidepsin.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Biomarkers Analysis.
    Análisis de Biomarcadores.
    E.3Principal inclusion criteria
    1)Voluntary written informed consent of the patient (both to participate
    in the study and to provide biopsy samples) obtained before any studyspecific
    procedure.
    2)Age ? 18 years.
    3)Eastern Cooperative Oncology Group (ECOG) performance status (PS)
    ? 2.
    4)Life expectancy ? 3 months.
    5)Histologically confirmed diagnosis of R/R AITL (eligibility needs to be
    confirmed by central pathological review.*)
    6)At least a two-week washout period since the end of the last therapy
    (six weeks for a prior nitrosourea-containing regimen), recovery to
    grade ? 1 from any non-hematological adverse event (AE) derived from
    previous treatment (excluding alopecia).
    7)Adequate bone marrow (BM), renal, hepatic, and metabolic function
    (assessed ? 14 days before inclusion in the study):
    a)Absolute neutrophil count (ANC) ? 1.0 × 109/L.
    Screening of ANC should be independent of granulocyte-colony
    stimulating factor (G-CSF) support for at least one week and of
    pegylated G-CSF for at least two weeks.
    b)Platelet count ? 75 × 109/L.
    c)Hemoglobin ? 9 g/dL.
    Patients may receive red blood cells (RBC) and/or erythropoietin (EPO)
    and/or platelet transfusions in accordance with institutional guidelines.
    d)Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
    ? 3.0 × the upper limit of normal (ULN).
    e)Total bilirubin ? 1.5 × ULN.
    f)Alkaline phosphatase (ALP) ? 3.0 × ULN (< 5 × ULN if isolated ALP
    increase, i.e., without ALT/AST or bilirubin increase).
    g)Calculated creatinine clearance (CrCL) ? 30 mL/minute (Cockcroft-
    Gault formula).
    h)Creatine phosphokinase (CPK) ? 2.5 × ULN.
    i)Albumin ? 2.5 g/dL.
    8)Left ventricular ejection fraction (LVEF) by echocardiogram (ECHO) or
    multiple-gated acquisition scan (MUGA) above the lower limit of normal
    (LLN) and not less than 45%.
    * Patient inclusion can be approved based on local histopathological
    report(s). Eligibility will be confirmed using diagnosis and/or relapse
    biopsy specimens submitted for central pathological review prior to each
    futility analysis/end of the study.
    1)Consentimiento informado por escrito otorgado voluntariamente (para
    participar en el estudio y proporcionar muestras de biopsia) obtenido
    antes de realizar cualquier procedimiento específico del estudio.
    2)Edad ? 18 años.
    3)Estado funcional (EF) en la escala del Eastern Cooperative Oncology
    Group (ECOG) ? 2.
    4)Esperanza de vida ? 3 meses.
    5)Diagnóstico de LAIT R/R histológicamente confirmado (es preciso que
    la revisión patológica central confirme la elegibilidad*).
    6)Un periodo de lavado farmacológico de, al menos, dos semanas desde
    el final del último tratamiento (seis semanas en caso de terapia previa
    con nitrosureas), recuperación a grado ? 1 de cualquier acontecimiento
    adverso (AA) no hematológico derivado de un tratamiento anterior
    (excluyendo alopecia).
    7)Función medular (MO), renal, hepática y metabólica adecuada
    (evaluadas ? 14 días antes de la inclusión en el estudio):
    a)Recuento absoluto de neutrófilos (RAN) ? 1,0 x 109/l.
    La selección de RAN debe ser independiente del apoyo con factor
    estimulador de colonias de granulocitos (FEC-G) durante, al menos, una
    semana y de FEC-G pegilado durante un mínimo de dos semanas.
    b)Número de plaquetas ? 75 × 109/l.
    c)Hemoglobina ? 9 g/dl.
    Los pacientes pueden recibir transfusiones de glóbulos rojos (GR) y/o
    eritropoyetina (EPO) y/o plaquetas de conformidad con las guías
    institucionales.
    d)Aspartato aminotransferasa (AST) y alanino aminotransferasa (ALT) ?
    3,0 × límite superior del valor normal (LSN).
    e)Bilirrubina total ? 1,5 × LSN.
    f)Fosfatasa alcalina (FA) ? 3,0 × LSN (< 5 × LSN si aumenta FA aislada,
    es decir, sin incremento de bilirrubina o ALT/AST).
    g)Aclaramiento de creatinina calculado (ACr) ? 30 ml/minuto (fórmula
    de Cockcroft-Gault).
    h)Creatina fosfoquinasa (CPK) ? 2,5 × LSN.
    i)Albúmina ? 2,5 g/dl.
    8)Fracción de eyección ventricular izquierda (FEVI) mediante
    ecocardiograma (ECO) o ventriculografía nuclear (MUGA) superior al
    límite inferior del valor normal (LIN) y mayor que el 45%.
    *La inclusión de sujetos se puede autorizar en base a los informes
    histopatológicos locales. Se confirmará la elegibilidad utilizando las
    muestras biópsicas del diagnótico y/o en recaída presentadas para la
    revisión patológica central antes de cada análisis de futilidad/final del
    estudio.
    E.4Principal exclusion criteria
    1)Concomitant diseases/conditions:
    a)History or presence of angina, myocardial infarction, clinically relevant
    valvular heart disease, uncontrolled hypertension, or congestive heart
    failure within the previous 12 months.
    b)Symptomatic arrhythmia (excluding grade ? 2 anemia-related sinusal
    tachycardia) or any arrhythmia requiring ongoing treatment, and/or
    prolonged grade ? 2 QT-QTc, or presence of unstable atrial fibrillation.
    Patients with stable atrial fibrillation on treatment are allowed provided
    they do not meet any other cardiac or prohibited drug exclusion
    criterion.
    c)Active uncontrolled infection. Active hepatitis B or C virus (HBV or
    HCV), or human immunodeficiency virus (HIV) infection.
    d)Morphological or cytological features of myelodysplasia and/or postchemotherapy
    aplasia on BM assessment.
    e)Myopathy > grade 2 or any clinical situation that causes significant
    and persistent elevation of CPK (> 2.5 × ULN in two different
    determinations performed one week apart).
    f)Limitation of the patient's ability to comply with the treatment or
    follow-up requirements.
    g)Diagnosis of another invasive malignancy unless free of disease for at least three years following therapy with curative intent. Patients with
    early-stage basal cell or squamous cell skin cancer, cervical
    intraepithelial neoplasia, cervical carcinoma in situ, or superficial
    bladder cancer, may be eligible to participate at the Investigator's
    discretion.
    h)Any other major illness that, in the Investigator's judgment, will
    substantially increase the risk associated with the patient's participation
    in this study.
    2)Central nervous system (CNS) involvement.
    3)Women who are pregnant or breast feeding. Fertile patients (men and
    women) who are not using an effective method of contraception. All
    patients (men and women) must agree to use an effective contraceptive
    measure (if applicable) up to six months after treatment discontinuation.
    4)Concomitant medications that include corticosteroids, chemotherapy,
    or other therapy that is or may be active against AITL, within the two
    weeks prior to treatment start. Concurrent corticosteroids are allowed,
    provided they are administered at an equivalent prednisone dose of ? 10
    mg daily, as premedication for blood products only.
    5)Major upper gastrointestinal bleeding episode occurring during the
    previous year before screening.
    6)Known hypersensitivity to plitidepsin or any of its formulation
    components.
    A total of 60 patients with AITL confirmed by central pathological review
    are to be included in this study (unless one of the two planned futility
    analyses stops recruitment after the inclusion of approximately 15 and
    30 patients).
    1)Afecciones/enfermedades concomitantes:
    a)Antecedentes o presencia de angina, infarto de miocardio, valvulopatía
    cardiaca clínicamente significativa, hipertensión no controlada o
    insuficiencia cardiaca congestiva en los 12 meses anteriores.
    b)Arritmia sintomática (excluyendo taquicardia sinusal relacionada con
    anemia de grado ? 2) o cualquier arritmia que requiere un tratamiento
    continuo y/o QT-QTc de grado ? 2 prolongado o presencia de fibrilación
    auricular inestable. Se permiten pacientes con fibrilación auricular
    estable que reciben tratamiento siempre y cuando no cumplan ningún
    otro criterio de exclusión por motivos cardiacos o fármacos prohibidos.
    c)Infección no controlada activa. Infección por el virus de la hepatitis B
    o C activa (VHB o VHC) o por el virus de la inmunodeficiencia humana
    (VIH).
    d)Características morfológicas o citológicas de mielodisplasia y/o
    aplasia postquimioterapéutica en la evaluación de MO.
    e)Miopatía de grado > 2 o cualquier situación clínica que produce una
    elevación significativa y persistente de CPK (> 2,5 × LSN en dos
    determinaciones diferentes realizadas con una semana de diferencia).
    f)Limitación de la capacidad del paciente para cumplir con los requisitos
    de tratamiento o seguimiento.
    g)Diagnóstico de otra neoplasia maligna invasiva a menos que no se
    padezca enfermedad durante, al menos, 3 años después de la terapia con
    intención curativa. Los pacientes con cáncer cutáneo de células
    escamosas o de células basales en estadio temprano, neoplasia maligna
    intraepitelial cervical, carcinoma de cuello uterino in situ o cáncer de
    vejiga superficial pueden ser elegibles para participar a discreción del
    Investigador.
    h)Cualquier otra enfermedad importante que, a juicio del Investigador,
    pudiera aumentar de manera sustancial los riesgos derivados de la
    participación del paciente en el estudio.
    2)Afectación del sistema nervioso central (SNC).
    3)Mujeres embarazadas o en período de lactancia. Pacientes fértiles
    (hombres y mujeres) que no emplean un método anticonceptivo eficaz.
    Todos los pacientes (hombres y mujeres) deben aceptar utilizar un método anticonceptivo eficaz (si fuera aplicable) durante un máximo de
    seis meses después de la suspensión del tratamiento.
    4)Fármacos concomitantes que incluyen corticoesteroides, quimioterapia
    u otro tratamiento que pueden ser activos frente a LAIT, en las dos
    semanas previas al inicio de la terapia. Se permiten corticoesteroides
    concurrentes, siempre que se administren a una dosis equivalente de
    prednisona de ? 10 mg al día, como premedicación para hemoderivados
    únicamente.
    5)Episodio hemorrágico gastrointestinal superior importante que se
    produce durante el año anterior a la selección.
    6)Hipersensibilidad conocida a plitidepsin o a alguno de los componentes
    de su formulación.
    E.5 End points
    E.5.1Primary end point(s)
    Overall response rate (ORR), defined as the percentage of patients with remission, either complete (CR) or partial remission (PR), according to the Lugano classification response criteria per independent review.
    An external IRC will assign the objective response and a progression or censoring date for each patient according to a predefined algorithm provided in a separate charter.
    Tasa de respuesta global (TRG), se define como el porcentaje de pacientes con remisión, ya sea remisión completa (RC) o parcial (RP) según los criterios de respuesta de la clasificación de Lugano conforme a una revisión independiente.
    Un CRI externo asignará la respuesta objetiva y una fecha de progresión o censura a cada paciente de acuerdo con un algoritmo predefinido dispuesto en un documento separado.
    E.5.1.1Timepoint(s) of evaluation of this end point
    During the Study.
    A lo largo del estudio.
    E.5.2Secondary end point(s)
    *ORR per Investigator assessment (IA).
    *CR rate, defined as the percentage of patients with complete remission according to the Lugano classification per IRC and per IA.
    *Duration of response (DoR), defined as the time from the date when the remission criteria (PR or CR, whichever is first achieved) are fulfilled to the first date when PD, recurrence or death (due to any cause) is documented. Response will be assessed according to Lugano classification and per IRC and IA.
    *Progression-free survival (PFS), defined as the time from the date of first drug administration to the date of PD, death (of any cause), or last tumor evaluation per IRC and IA.
    *Progression-free survival at 6/12 months (PFS6/PFS12), defined as the Kaplan-Meier estimate of the percentage of patients who are progression-free at six/twelve months after the first drug administration per IRC and IA.
    *Intrapatient PFS/TTP, defined as the ratio of PFS achieved with the experimental treatment versus prior last TTP in the R/R setting.
    *Overall survival (OS), defined as the time from the date of the first dose to the date of death (of any cause) or last patient contact.
    *Overall survival at 6/12 months (OS6/OS12), defined as the Kaplan-Meier estimate of the percentage of patients who are alive at six/twelve months after first drug administration.
    *Treatment safety [AEs, serious adverse events (SAEs) and laboratory abnormalities] graded according to the NCI-CTCAE, v.4. Dose reductions, omitted doses or cycle delays due to treatment-related AEs, and reasons for treatment discontinuations will be analyzed.
    *Pharmacokinetics (PK), samples for PK analysis will be obtained during Cycle 1 exclusively.
    *Exploratory Biomarker Analysis, biopsy samples (initial and relapse) and blood samples will be analyzed in order to examine any correlation of efficacy with molecular markers related to the mechanism of action of plitidepsin or to the pathogenesis of the disease.

    A total of 60 patients with AITL confirmed by central pathological review will be treated, 19 or more responders will be needed to get an overall estimate for response rate higher than 30% and its lower limit for the 95% confidence interval (CI) greater than 20% (31.7% CI95% 20.3?45.0% following the binomial distribution).

    Two futility analyses of the primary endpoint (ORR according to the Lugano classification response criteria per independent review) are planned to reject the alternative hypothesis around six months after approximately 25% and 50% of eligible patients have been treated (15 and 30 patients, respectively).
    *TRG conforme a la evaluación del investigador (EI).
    *Tasa de RC, se define como el porcentaje de pacientes con remisión completa según la clasificación de Lugano acorde al CRI y a la EI.
    *Duración de la respuesta (DDR), se define como el tiempo desde la fecha en la que se cumplen los criterios de remisión (RP o RC, lo que se consiga primero) hasta la primera fecha en la que se documenta PE, recurrencia o muerte (por cualquier causa). La respuesta se valorará conforme a la clasificación de Lugano y de acuerdo al CRI y EI.
    *Supervivencia libre de progresión (SLP), se define como el tiempo desde la fecha de la primera administración del fármaco hasta la fecha en la que se produce la PE, muerte (por cualquier causa) o de la última evaluación tumoral según el CRI y EI.
    *Supervivencia libre de progresión a los 6/12 meses (SLP6/SLP12), se define como la estimación de Kaplan-Meier del porcentaje de sujetos que no presentan progresión a los seis/doce meses después de la primera administración del fármaco según el CRI y EI.
    *SLP/TTP intrapaciente, se define como el cociente de SLP lograda con el tratamiento experimental frente al último TTP previo en el entorno R/R.
    *Supervivencia global (SG), se define como el tiempo desde la fecha de la primera dosis hasta la fecha en la que se produce la muerte (por cualquier causa) o el último contacto del paciente.
    *Supervivencia global a los 6/12 meses (SG6/SG12), se define como la estimación de Kaplan-Meier del porcentaje de pacientes con vida a los seis/doce meses después de la primera administración del fármaco.
    *Seguridad del tratamiento [AA, acontecimientos adversos graves (AAG) y anomalías de laboratorio] graduado de acuerdo con los criterios NCI-CTCAE, v.4. Se analizarán las reducciones de la dosis, omisión de las dosis o retrasos del ciclo a causa de AA relacionados con el tratamiento, así como las razones por las que se produce la interrupción del tratamiento.
    *Farmacocinética (FC), las muestras para el análisis FC se obtendrán solo durante el Ciclo 1.
    *Análisis de biomarcadores exploratorios, las muestras biópsicas (inicial y en la recaída) y las muestras de sangre se analizarán con el fin de estudiar cualquier correlación de eficacia con marcadores moleculares en relación con el mecanismo de acción de plitidepsin o con la patogenia de la enfermedad.

    Un total de 60 pacientes con LAIT confirmado mediante revisión patológica central recibirá tratamiento, se necesitarán 19 o más respondedores para obtener una estimación general de una tasa de respuesta superior al 30% y el nivel inferior para el intervalo de confianza (IC) al 95% será mayor del 20% (31,7% IC95% 20,3%?45,0% tras la distribución binomial).

    Se ha planificado la realización de dos análisis de futilidad del criterio principal de valoración (TRG según los criterios de respuesta de la clasificación de Lugano conforme a una revisión independiente) para rechazar la hipótesis alternativa alrededor de seis meses después del tratamiento de, aproximadamente, el 25% y el 50% de pacientes elegibles (15 y 30 sujetos, respectivamente).
    E.5.2.1Timepoint(s) of evaluation of this end point
    During the study.
    A lo largo del estudio.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Biomarker Analysis.
    Análisis de 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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA16
    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
    Switzerland
    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
    12 months after the last patients inclusion. If there are patients still being treated at the planned cutoff date, the actual cutoff date will be the date when those patients have completed the ongoing treatment cycle and the corresponding EOT visit.
    12 meses después de la inclusión del último paciente. Si hay pacientes que siguen recibiendo tratamiento en la fecha límite planificada, la fecha de corte real se determinará como la fecha en la que esos sujetos han completado el ciclo terapéutico en curso y han realizado la visita de FDT correspondiente.
    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 months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 24
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 36
    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 No
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state19
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 41
    F.4.2.2In the whole clinical trial 60
    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)
    After EOT, patients will be followed every four weeks until resolution or stabilization of toxicities (if any). Patients who discontinue treatment without disease progression will be followed every eight weeks (± two weeks) until PD, start of other antitumor therapy, death or the date of study termination (clinical cutoff), whichever occurs first.
    Después del FDT, se realizará un seguimiento de los pacientes cada cuatro semanas hasta la resolución o estabilización de las toxicidades (si las hubiera). Los sujetos que interrumpen el tratamiento sin presentar progresión de la enfermedad se someterán a seguimiento cada ocho semanas (± dos semanas) hasta la PE, inicio de otro tratamiento antitumoral, muerte o fecha de finalización del estudio (punto de corte clínico), lo que ocurra primero.
    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 Decision2016-03-14
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-03-04
    P. End of Trial
    P.End of Trial StatusOngoing
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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