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    EudraCT Number:2017-001842-82
    Sponsor's Protocol Code Number:W00101-IV-1-01
    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:2017-08-10
    Trial results
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    A. Protocol Information
    A.1Member State ConcernedSpain - AEMPS
    A.2EudraCT number2017-001842-82
    A.3Full title of the trial
    Phase I/II open label dose escalation and dose expansion study of intravenous infusion of W0101, an antibody-drug conjugate, in patients with advanced or metastatic solid tumors.
    International, multicenter, open label study.
    Estudio abierto en fase I/II de aumento escalonado de la dosis y ampliación de la dosis de una infusión intravenosa de W0101, un conjugado anticuerpo-fármaco, en pacientes con tumores sólidos avanzados o metastásicos.
    Estudio abierto, multicéntrico, internacional.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A research study of a new investigational medicinal product for the
    treatment of patients with advanced or metastatic solid tumors
    Un estudio de investigación sobre un nuevo medicamento experimental para el tratamiento de pacientes con tumores sólidos avanzados o metastásicos.
    A.4.1Sponsor's protocol code numberW00101-IV-1-01
    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.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 supportPIERRE FABRE MEDICAMENT
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPIERRE FABRE MEDICAMENT
    B.5.2Functional name of contact pointDr Karim KEDDAD
    B.5.3 Address:
    B.5.3.1Street Address3 Avenue Hubert Curien
    B.5.3.2Town/ cityToulouse Cedex 1
    B.5.3.3Post code31035
    B.5.4Telephone number+34534 50 61 69
    B.5.5Fax number+33534 50 65 92
    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 nameW0101
    D.3.2Product code W0101
    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 INNUnavailable
    D.3.9.1CAS number Unavailable
    D.3.9.2Current sponsor codeW0101
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D. cell therapy medicinal product No
    D. therapy medical product No
    D. Engineered Product No
    D. ATIMP (i.e. one involving a medical device) No
    D. on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Advanced or metastatic solid tumors (excluding lymphoma)
    Tumores sólidos avanzados o metastásicos (excluyendo linfoma)
    E.1.1.1Medical condition in easily understood language
    Advanced or metastatic solid tumors (excluding lymphoma)
    Tumores sólidos avanzados o metastásicos (excluyendo linfoma)
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10065252
    E.1.2Term Solid tumor
    E.1.2System Organ Class 100000020962
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Dose escalation phase :
    To determine the Maximum Tolerated Dose and schedule (MTDS) and to characterize the dose-limiting toxicities (DLTs), following administration of W0101 given as monotherapy intravenous infusion.

    Dose expansion phase:
    To evaluate the efficacy by Overall Response Rate [ORR%] in subjects with specific tumor types selected through high expression of IGF-1R
    Fase de aumento escalonado de la dosis:
    Determinar la dosis máxima tolerada (DMT) y su calendario de administración, y caracterizar las toxicidades limitantes de la dosis (TLD) tras la administración de W0101 como infusión intravenosa en régimen de monoterapia.

    Fase de cohortes de ampliación:
    Evaluar la eficacia por tasa de respuesta objetiva [%TRO] en sujetos con determinados tipos de tumores seleccionados a partir de una expresión elevada del IGF-1R.
    E.2.2Secondary objectives of the trial
    Dose escalation phase :
    To evaluate the safety and tolerability of W0101
    To evaluate preliminary antitumor activity
    To characterize the pharmacokinetics (PK)
    To describe the immunogenicity
    To determine the Recommended Dose for Expansion (RDE) cohorts

    Dose expansion phase :
    To evaluate the safety and tolerability profile
    To characterize the preliminary antitumor activity by evaluation of progression free survival [PFS] and duration of response [DoR] in subjects with specific tumor types selected through high expression of IGF-1R
    To characterize the pharmacokinetics (PK)
    To evaluate the immunogenicity
    Fase de aumento escalonado de la dosis:
    Evaluar la seguridad y la tolerabilidad del W0101.
    Evaluar la actividad antitumoral preliminar.
    Caracterizar la farmacocinética (FC).
    Describir el potencial inmunógeno.
    Determinar las cohortes de dosis recomendada para ampliación (DRA).

    Fase de cohortes de ampliación:
    Evaluar el perfil de seguridad y tolerabilidad.
    Caracterizar la actividad antitumoral preliminar mediante la evaluación de la supervivencia sin progresión (SSP) y de la duración de la respuesta (DdR) en sujetos con determinados tipos de tumor, seleccionados por su expresión elevada del IGF-1R.
    Caracterizar la farmacocinética (FC).
    Evaluar el potencial inmunógeno.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female subjects age ≥ 18 years
    2. Subjects with histologically or cytologically confirmed advanced or metastatic solid tumors (excluding lymphoma), unresponsive to standard treatment or for whom no standard treatment is available or appropriate
    Note: preferentially squamous non-small cell lung cancer, larynx carcinoma, ER positive breast cancer and soft tissue sarcomas
    3. Formalin-fixed paraffin-embedded (FFPE) archived tumor tissue block available (cohorts A1 and A2) for retrospective assessment of IGF-1R status
    4. ECOG performance status 0 or 1
    5. Adequate bone marrow at screening and at baseline
    i. Absolute neutrophil count (ANC) ≥ 1,500/mm3
    ii. Platelet count ≥ 150,000/mm3
    iii. Hemoglobin ≥ 9g/dL(6.2 mmol/L)
    Note: Any blood product transfusion is prohibited within 2 weeks before the first study treatment administration.
    6. Adequate liver function at screening and at baseline
    i. Total Bilirubin ≤ 1.5 mg/dL (≤26µmol/L, SI unit equivalent)
    ii. AST and ALT ≤ 3 upper limit of normal (ULN), ULN ≤ 5 in case of liver metastasis
    iii. For subjects with Gilbert’s syndrome: total bilirubin <2.5 ULN
    7. Adequate renal function at screening and at baseline
    Note: Serum creatinine ≤ 1.5 normal institutional limits or calculated (Cockroft- Gault) creatinine clearance ≥ 60 mL/min for subjects with creatinine levels above 1.5 normal institutional limits
    8. Serum calcium potassium and magnesium within normal ranges as per local lab values at screening and at baseline.
    Note: Subjects with electrolyte (calcium potassium and magnesium) grade 1 alterations considered as not clinically significant as per the investigator assessment may be eligible for the study.
    9. Subject must have recovered from all toxicities from previous cancer therapies toxicity to at least grade 1 (except alopecia)
    10. Subject must have measurable disease as per RECIST v1.1 criteria
    11. Non pregnant and adequate method of contraception for female subject of child-bearing potential:
    i. Negative serum beta human chorionic gonadotropin (β-HCG) test or negative urine pregnancy test within 72h prior first study treatment administration.
    ii. Use of an effective method of contraception (hormonal contraception or intra-uterine device) assessed by the investigator, for at least 2 months before the first study treatment administration, and agreement to go on using it during the whole duration of the study and up to 3 month after the last dose of the study treatment
    Note: a female subject of child-bearing potential is a woman who is not permanently sterilized or not postmenopausal (post-menopausal is defined as 12 months with no menses without an alternative medical cause).
    12. Adequate method of contraception for fertile male with a child-bearing potential partner.
    Note: Use of double barrier contraception method (use of condom for male and effective contraception method for the partner) from the entire duration of the study to 3 months after the last dose of the study treatment.
    13. Having signed his/her written informed consent, prior to any screening procedure
    14. Affiliated or beneficiary of a social security system, (if applicable in the national regulation)
    + Expansion cohorts phase (II)
    The same inclusion criteria listed above apply for expansion cohort phase, except for inclusion criteria 2 and 3, which are replaced by:
    2. Subjects with histologically or cytologically confirmed advanced or metastatic specific solid tumor
    3. Subject must have documented IGF1-R positive tumor as assessed prospectively by central IHC test on an archival tumor sample of less than 1 year old or on a tumor biopsy taken at screening
    1. Hombres y mujeres de ≥ 18 años.
    2. Sujetos con tumores sólidos avanzados o metastásicos (salvo linfoma) confirmados histológica o citológicamente que no respondan al tratamiento estándar o para quienes el tratamiento estándar no esté disponible o no sea adecuado.
    Nota: preferiblemente carcinoma epidermoide de pulmón no microcítico, carcinoma de laringe, cáncer de mama positivo para receptores de estrógenos y sarcoma de tejidos blancos.
    3. Bloque de tejido tumoral archivado fijado en formol e incluido en parafina (FFIP) disponible (cohortes A1 y A2), para evaluación retrospectiva del estado de IGF-1R.
    4. Estado funcional del ECOG de 0 o 1.
    5. Médula ósea adecuada en las visitas de selección y basal.
    i. Cifras absolutas de neutrófilos (CAN) ≥1500/mm3.
    ii. Recuento plaquetario ≥150 000/mm3.
    iii. Hemoglobina ≥ 9 g/dL(6,2 mmol/L).
    Nota: queda prohibida la transfusión de cualquier producto sanguíneo en las 2 semanas anteriores a la primera administración del tratamiento del estudio.
    6. Función hepática adecuada en las visitas de selección y basal.
    i. Bilirrubina total ≤ 1,5 mg/dL (≤26 μmol/L, equivalente de unidad SI).
    ii. Límite superior de la normalidad (LSN) de ASAT y ALAT ≤ 3, LSN ≤ 5 en caso de metástasis hepática.
    iii. Para sujetos con síndrome de Gilbert: bilirrubina total <2,5 LSN.
    7. Función renal adecuada en las visitas de selección y basal.
    Nota: Creatinina sérica ≤ 1,5 veces los límites institucionales normales, o aclaramiento de creatinina calculado (Cockroft-Gault) ≥ 60 mL/min para sujetos con niveles de creatinina superiores a 1,5 veces los límites institucionales normales.
    8. Calcio, potasio y magnesio en suero comprendidos en los rangos normales, según valores del laboratorio local, en las visitas de selección y basal.
    Nota: podrán ser elegibles para el estudio los sujetos con alteraciones de electrolitos (calcio, potasio y magnesio) de grado 1 consideradas clínicamente no significativas según evaluación del investigador.
    9. El sujeto deberá haberse recuperado de todas las toxicidades derivadas de tratamientos anticáncer anteriores hasta al menos un grado 1 (salvo alopecia).
    10. Los sujetos deben presentar síntomas de enfermedad medibles según los criterios RECIST v1.1.
    11. Ausencia de embarazo y método anticonceptivo adecuado en el caso de las mujeres susceptibles de quedar embarazadas:
    i. Prueba de gonadotropina coriónica humana β (β-hCG) negativa o prueba de embarazo en orina negativa en las 72 h anteriores a la administración del primer tratamiento del estudio.
    ii. Uso de un método anticonceptivo eficaz (anticonceptivos hormonales o dispositivo intrauterino [DIU]) evaluado por el investigador durante al menos los 2 meses anteriores a la primera administración del tratamiento del estudio, y aceptación de seguir utilizándolo durante todo el estudio y hasta 3 meses después de la última dosis del tratamiento del estudio.
    Nota: se considerarán mujeres susceptibles de quedar embarazadas todas aquellas mujeres no esterilizadas de forma permanente o no posmenopáusicas (definiéndose la posmenopausia como un periodo de 12 meses de amenorrea sin causa médica alternativa).
    12. Método adecuado de anticoncepción en el caso de pacientes fértiles con pareja susceptible de quedar embarazada.
    Nota: uso de un método anticonceptivo de doble barrera (uso de preservativo en el caso del hombre y método anticonceptivo para la pareja) durante todo el estudio y en los 3 meses posteriores a la última dosis del tratamiento del estudio.
    13. Haber firmado el consentimiento informado con carácter previo a cualquier procedimiento de selección.
    14. Afiliado o beneficiario de un sistema de seguridad social (si procede según la normativa nacional).

    + Fase (II) de cohortes de ampliación:
    Se aplicarán los mismos criterios de inclusión/exclusión enumerados anteriormente, a excepción de los criterios de inclusión 2 y 3, que se sustituirán por:
    2. Sujetos con determinados tumores sólidos avanzados o metastásicos confirmados histológica o citológicamente.
    3. El sujeto deberá presentar un tumor positivo para IGF1-R documentado, según evaluación prospectiva mediante prueba IHQ en una muestra tumoral de archivo de menos de 1 año de antigüedad o en una biopsia tumoral obtenida en la selección.
    E.4Principal exclusion criteria
    1. History of anti-cancer therapies within 4 weeks (or ≤ 5 half lives for targeted agents) of initiating study treatment
    Note: Anti-cancer therapies are defined as: major surgery, radiotherapy (palliative setting is allowed), hormone therapy (except treatment for prostatic and breast cancer), immunotherapy, any conventional cytotoxic chemotherapy or other anti-cancer treatments
    2. Known active or uncontrolled infections (bacterial, fungal, viral including HBV and HCV infections)
    3. Symptomatic brain metastases, CNS tumors
    4. Symptomatic motor or sensory peripheral neuropathy (≥ grade 2)
    5. Subjects having ophthalmologic abnormalities
    Note: Ophthalmologic abnormalities are defined as subjects with monocular vision or having media opacities or any other condition that precludes monitoring of the retina or the fundus or having a history or current ophthalmology exam with retina or cornea abnormalities, especially central serous retinopathy, age related macular degeneration, retina degradation, corneal ulcers, cornea dystrophies or other pathology at the discretion of the ophthalmologist/investigator.
    6. Active serious systemic disease (infection,organic or dysmetabolic desease)
    7. Subjects with uncontrolled high blood pressure
    Note: systolic blood pressure, SBP >150 mmHg and/or diastolic blood pressure, DBP > 95 mmHg despite treatment on 2 out of 3 determinations done in case that the first one meets the criterion for exclusion
    8. Type 1 diabetes or type 2 diabetes that is poorly controlled according to the investigator’s judgment
    i. Hb A1C ≥ 7%
    ii. Diabetes mellitus requiring insulin treatment
    iii. Diabetes mellitus with clinical signs
    iv. Fasting Plasma Glucose (FPG) ≥ 140 mg/dL / 7.8 mmol/L
    9. Serum albumin < 30 g/L
    10. History of another malignancy
    Note: except adequately treated in situ carcinoma of the cervix or non-melanoma carcinoma of the skin, or any other curatively treated malignancy that has not been treated or recurred in the prior 3 years.
    11. Biologic therapy (eg, antibodies), including ADCs: ≤ 4 weeks before first study treatment administration.
    12. Participation into a clinical study of an investigational agent within 4 weeks before the first study treatment administration.
    Note: Subjects participating in the follow up period of previous studies (with no drug administration) may be eligible for the study.
    13. Left ventricular ejection fraction (LVEF) < 45% as determined by MUGA scan or echography at screening
    14. QTc > 470 msec on screening ECG or congenital long QT syndrome
    15. Subjects who have any medical condition that would, in the investigator’s judgment, prevent the subject’s participation in the clinical study due to safety concerns or compliance with clinical study procedures.
    Note: Any severe, acute, or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study treatment administration or that may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for the study
    16. Prior anti IGF-1R therapy
    17. Subject liable not to comply with protocol instructions in the investigator’s opinion
    18. Subject linguistically or mentally unable to understand the nature, objectives and possible consequences of the trial, or refusing to subject himself/herself to its constraints
    19. Subject family member or work associate (secretary, nurse, technician,..) of the Investigator
    20. Subject having forfeited his / her freedom by administrative or legal award or being under guardianship
    21. Female subject pregnant or lactating
    22. Known hypersensitivity to drug or metabolites of similar chemical classes
    1. Historial de tratamientos anticáncer en las 4 semanas (o periodo igual o superior a 5 semividas en el caso de agentes específicos) anteriores al inicio del tratamiento del estudio.
    Nota: se entenderá por tratamientos anticáncer: cirugía mayor, radioterapia (contexto paliativo admitido), terapia hormonal (salvo tratamiento para cáncer de próstata y de mama), inmunoterapia, o cualquier quimioterapia antineoplásica u otros tratamientos anticáncer convencionales.
    2. Infecciones conocidas, activas o no controladas (bacterianas, fúngicas, víricas, incluidas infecciones VHB y VHC).
    3. Metástasis cerebrales sintomáticas, tumores del SNC.
    4. Neuropatía motora o sensorial sintomática (grado ≥ 2).
    5. Sujetos con anomalías oftalmológicas.
    Nota: se entiende por anomalías oftalmológicas: sujetos con visión monocular u opacidades del medio, o cualquier otra afección que requiera control de la retina o del fondo, o con historial o examen oftalmológico actual de anomalías en la retina o en la córnea, especialmente retinopatía serosa central, deterioro macular asociado a la edad, deterioro de la retina, úlceras corneales, distrofias de la córnea u otras patologías, a discreción del oftalmólogo/investigador.
    6. Enfermedad sistémica grave activa (infección, enfermedad orgánica o disfunción metabólica).
    7. Sujetos con presión arterial alta no controlada.
    Nota: presión arterial sistólica, PAS >150 mmHg o presión arterial diastólica, PAD > 95 mmHg a pesar del tratamiento en 2 de 3 determinaciones realizadas en el caso de que la primera cumpla los criterios de exclusión.
    8. Diabetes de tipo 1 o diabetes de tipo 2 escasamente controlada según el criterio del investigador.
    i. Hb A1C ≥ 7%.
    ii. Diabetes mellitus que requiera tratamiento con insulina.
    iii. Diabetes mellitus con síntomas clínicos.
    iv. Glucosa plasmática en ayunas (FPG) ≥ 140 mg/dL/7,8 mmol/L.
    9. Albúmina sérica < 30 g/L.
    10. Antecedentes de otras neoplasias malignas.
    Nota: salvo carcinoma del cuello uterino o carcinoma de piel no melanómico debidamente tratado in situ, o cualquier otra neoplasia maligna tratada de forma curativa que no se haya tratado o no haya mostrado recidiva en los últimos 3 años.
    11. Tratamiento con fármacos biológicos (p. ej., anticuerpos), incluidos CAF: ≤ 4 semanas antes de la administración del primer tratamiento del estudio.
    12. Participación en un estudio clínico de un agente en fase de investigación en las 4 semanas anteriores a la primera administración del tratamiento del estudio.
    Nota: podrán ser elegibles para el estudio los sujetos que participen en el periodo de seguimiento de estudios anteriores (sin administración de fármacos).
    13. Fracción de eyección ventricular izquierda (FEVI) < 45 %, determinada mediante exploración MUGA o ecografía en el momento de la selección.
    14. QTc > 470 ms en el ECG de selección, o síndrome del QT largo congénito.
    15. Sujetos que presenten cualquier afección médica que, según criterio del investigador, pudiera impedir la participación del sujeto en el estudio clínico por motivos de seguridad o de conformidad con los procedimientos del estudio clínico.
    Nota: cualquier afección médica o psiquiátrica o anomalía de laboratorio grave, aguda o crónica que pudiera incrementar el riesgo asociado a la participación en el estudio o a la administración del tratamiento del estudio, o que pudiera interferir en la interpretación de los resultados y que, a criterio del investigador, convirtiese al sujeto en no apto para el estudio.
    16. Tratamiento anti IGF-1R anterior.
    17. Sujeto responsable de no cumplir las instrucciones del protocolo en opinión del investigador.
    18. Sujeto lingüística o mentalmente incapaz de entender la naturaleza, los objetivos y las posibles consecuencias del ensayo, o de negarse por mí mismo a someterse a sus restricciones.
    19. El sujeto es familiar o compañero de trabajo (secretario, miembro del personal de enfermería, técnico, etc.) del investigador.
    20. Sujeto cuya libertad está restringida por decisión administrativa o legal, o sujeto tutelado.
    21. Mujeres embarazadas o en periodo de lactancia.
    22. Hipersensibilidad conocida a fármacos o metabolitos de clases químicas similares.
    E.5 End points
    E.5.1Primary end point(s)
    Dose escalation phase :
    Dose-limiting toxicities (DLTs)

    Dose expansion phase :
    Overall Response Rate ORR [Complete Response + Partial Response] as determined by RECIST v1.1
    Fase de aumento escalonado de la dosis:
    Toxicidades limitantes de la dosis (TLD).

    Fase de cohortes de ampliación:
    Tasa de respuesta objetiva TRO (Respuesta completa + Respuesta parcial) determinado por RECIST v1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    Dose escalation phase :
    Will be assesed during the DLT evaluation periods

    Dose expansion phase :
    Will be assessed every 6 weeks
    Fase de aumento escalonado de la dosis:
    Se analizará durante los periodos de evaluación TLD.

    Fase de cohortes de ampliación:
    Se analizará cada 6 semanas.
    E.5.2Secondary end point(s)
    Dose escalation phase :
    - Safety and tolerability profile caracterized by type frequency, severity, intensity (graded by NCI CTCAE version 4.03)
    - ORR [CR+PR] as determined by RECIST v1.1
    - PK parameters
    - HAHA levels

    Dose expansion phase :
    - Safety and tolerability profile caracterized by type frequency, severity, intensity (graded by NCI CTCAE version 4.03)
    - Progression Free Survival (PFS)
    - Duration of Response (DoR)
    - PK parameters
    - HAHA levels
    Fase de aumento escalonado de la dosis:
    - Perfil de seguridad y tolerabilidad caracterizado por la frecuencia tipo, severidad, intensidad (de acuerdo con los criterios NCI CTCAE, versión 4.03).
    - TRO (RC + RP) determinado por RECIST v1.1
    - Parámetros de FC
    - Niveles HAHA

    Fase de cohortes de ampliación:
    - Perfil de seguridad y tolerabilidad caracterizado por la frecuencia tipo, severidad, intensidad (de acuerdo con los criterios NCI CTCAE, versión 4.03).
    - Supervivencia sin progresión (SSP)
    - Duración de la respuesta (DdR)
    - Parámetros de FC
    - Niveles HAHA
    E.5.2.1Timepoint(s) of evaluation of this end point
    Along 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 No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) Yes
    E.7.1.1First administration to humans Yes
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E. 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) Information not present in EudraCT
    E.8.2.2Placebo Information not present in EudraCT
    E.8.2.3Other Information not present in EudraCT
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA3
    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
    The end of study is defined as the last follow up visit for the last subject (safety follow-up or efficacy follow-up whichever comes last)
    El final del estudio se define como la última visita de seguimiento del ultimo paciente (seguimiento de seguridad o seguimiento de eficacia, lo que ocurra más tarde).
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months8
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years4
    E.8.9.2In all countries concerned by the trial months8
    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: 205
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 111
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state32
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 316
    F.4.2.2In the whole clinical trial 316
    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)
    Follow-up will be performed every 6 weeks for every subject who has not progressed at the time of discontinuation of study treatment until disease progression is reported, initiation of subsequent anticancer therapies, Lost to Follow-up or death, whichever occurs first
    Se hará seguimiento cada 6 semanas para cada paciente que no ha progresado en el momento de suspender el tratamiento del estudio hasta que se notifique la progresion de la enfermedad, inicio de las posteriores terapias anticancer, pérdida de seguimiento o fallecimiento, 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 Decision2017-11-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-10-06
    P. End of Trial
    P.End of Trial StatusOngoing
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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