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    Summary
    EudraCT Number:2005-005484-28
    Sponsor's Protocol Code Number:20050190
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2007-09-18
    Trial results View 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 number2005-005484-28
    A.3Full title of the trial
    Estudio multicéntrico, abierto, aleatorizado de AMG 951 en sujetos con cáncer de pulmón de células no pequeñas (CPCNP) en estadio IIIb/IV, que no han recibido tratamiento previo, tratados con quimioterapia con o sin bevacizumab.
    A.4.1Sponsor's protocol code number20050190
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorAmgen Inc.
    B.1.3.4CountryUnited States
    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 support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    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 nameApo2L/TRAIL (AMG951)
    D.3.2Product code AMG 951
    D.3.4Pharmaceutical form Powder for infusion*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeAMG 951
    D.3.9.3Other descriptive nameApo2L/TRAIL
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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.IMP: 2
    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 Yes
    D.2.1.1.1Trade name Avastin
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Ltd
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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 nameBevacizumab
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    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 INNBevacizumab
    D.3.9.3Other descriptive nameAvastin
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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.IMP: 3
    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 nameApo2L/TRAIL (AMG 951)
    D.3.2Product code AMG 951
    D.3.4Pharmaceutical form Powder for infusion*
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.9.2Current sponsor codeAMG 951
    D.3.9.3Other descriptive nameApo2L/TRAIL
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    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) Information not present in EudraCT
    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 Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    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 Information not present in EudraCT
    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
    Sujetos con cáncer de pulmón de células no pequeñas (CPCNP) en estadio IIIb/IV, que no han recibido tratamiento previo, tratados con quimioterapia con o sin bevacizumab.
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 8.1
    E.1.2Level LLT
    E.1.2Classification code 10029521
    E.1.2Term Non-small cell lung cancer stage IIIB
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 9.1
    E.1.2Level LLT
    E.1.2Classification code 10029522
    E.1.2Term Non-small cell lung cancer stage IV
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Objetivo primario:

    Fase 1b:
    Determinar la dosis máxima tolerada (DMT) (hasta 8 mg/kg/día durante 5 días de tratamiento y hasta 20 mg/kg/día durante 2 días de tratamiento) mediante la seguridad y la tolerabilidad de dosis múltiples de AMG 951 administrado por infusión intravenosa (i.v.), combinado con quimioterapia y bevacizumab, a sujetos con CPCNP.

    Fase 2:
    Evaluar la tasa de respuesta objetiva (respuesta completa [RC] y respuesta parcial [RP]) mediante RECIST modificados para AMG 951, con diversas pautas posológicas, combinado con carboplatino/paclitaxel ± bevacizumab en sujetos con CPCNP.
    E.2.2Secondary objectives of the trial
    Objetivo secundario de la fase 1b:
    Caracterizar la farmacocinética de AMG 951 (incluyendo, entre otros parámetros, el AUC, la Cmáx, la t1/2, el aclaramiento y el volumen de distribución).

    Objetivos secundarios de la fase 2:
    Evaluar la tasa de respuesta global (RC, RP y EE), la supervivencia libre de progresión (SLP), el tiempo hasta la respuesta, la duración de la respuesta, el tiempo hasta la progresión (THP) y la supervivencia global para AMG 951 con diversas pautas posológicas.

    Evaluar el perfil de seguridad de AMG 951 con diversas pautas posológicas.

    Evaluar la formación de anticuerpos anti-AMG 951.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Relacionados con la enfermedad
    •Cáncer de pulmón de células no pequeñas (CPCNP) confirmado histológicamente o citológicamente. Los tumores mixtos se clasificarán por el tipo de célula predominante a no ser que presenten elementos celulares pequeños en cuyo caso el paciente es inelegible. Los elementos citológicos o histológicos pueden determinarse en aspirados de las metástasis tumorales o biopsias.
    •Los sujetos deben padecer CPCNP avanzado definido como de estadio IIIb con derrame pleural maligno o de estadio IV o enfermedad recurrente. En la fase 1b del estudio pueden incluirse sujetos con enfermedad no medible pero evaluable, pero en la fase 2 del estudio sólo pueden incluirse aquellos cuya enfermedad sea medible.
    •Planificación para recibir hasta 6 ciclos de quimioterapia.
    •Estado de actividad ECOG (Eastern Cooperative Oncology Group) de 0 a 1 (véase el apéndice F).
    •Esperanza de vida superior a 3 meses.
    Datos demográficos
    •>= 18 años de edad y mayor de edad para dar el consentimiento informado.
    •Los sujetos deben firmar y fechar un Documento de consentimiento informado por escrito aprobado por el Comité ético independiente (CEI).
    Pruebas analíticas
    •INR <=1,2 y TTP que no supere el LSN en la semana previa a la inclusión.
    E.4Principal exclusion criteria
    Relacionados con la enfermedad
    •Neoplasia maligna previa distinta de CPCNP (excepto carcinoma de células basales in situ o el cáncer cervical in situ), a no ser que el sujeto haya sido tratado con intención curativa y no presente indicios de enfermedad durante >=3 años.
    • Metástasis en el sistema nervioso central (SNC) sin tratar o inestables. Los sujetos con metástasis en el SNC tratadas, controladas y estables son elegibles para las cohortes A y B de la parte del estudio correspondiente a la fase 2 si ha sido administrada una terapia definitiva (cirugía y/o radioterapia), no hay tratamiento planificado para las metástasis cerebrales y el sujeto está estable clínicamente y sin corticoides o dosis estable de corticoides durante al menos las 2 semanas anteriores a la inclusión.
    •Infarto de miocardio, o enfermedad inestable o no controlada asociada a la función cardiaca o que afecta a la misma (p. ej., angina inestable, insuficiencia cardiaca congestiva [New York Heart Association > clase II]) dentro del año anterior a la inclusión.
    •Hipertensión incontrolada definida como: Presión sanguínea sistólica >=150 mm Hg O presión sanguínea diastólica >=100 mm Hg (está permitido el tratamiento con antihipertensivos para lograr estos parámetros).
    •Antecedentes de trombosis arterial, embolia pulmonar, trombosis venosa profunda o trastornos hemorrágicos dentro del año anterior a la inclusión.
    •Cirugía mayor reciente dentro de los 28 días anteriores a la inclusión.
    •Los sujetos no deben padecer una úlcera grave con heridas sin cicatrizar o presentar una fractura ósea dentro de los 21 días anteriores a la inclusión.
    •Antecedentes persistentes de hemoptisis macroscópica (definida como ½ cucharadita o más de sangre roja brillante) relacionada con el CPCNP del sujeto.
    •Infección por VIH conocida (documentada en la historia clínica).
    •Infección activa el día de la inclusión.
    •Positivo conocido en las pruebas de la hepatitis C o positivo en las pruebas del antígeno de superficie de la hepatitis B.
    •Sujetos con síndrome de Gilbert.
    Pruebas analíticas
    •Recuento absoluto de neutrófilos (RAN) < 1,5 x 10e9/l (sin apoyo con factor estimulante de las colonias de granulocitos dentro de las 2 semanas anteriores a la inclusión).
    •Recuento de plaquetas < 100 x 10e9/L (sin transfusión en las 2 semanas anteriores a la inclusión).
    •Hemoglobina < 9 g/dL (los sujetos pueden recibir transfusiones o tratamiento eritropoyético para cumplir el criterio).
    •Valor cuantitativo de proteinuria > 1+ en la tira reactiva o >=30 mg/dl en el análisis de orina. El sujeto puede incluirse si la proteína cuantitativa es < 500 mg en una muestra de orina de 24 horas.
    •Disfunción hepática significativa definida como aspartato aminotransferasa (AST) o alanina aminotransferasa (ALT) > 2,5 x límites superiores de la normalidad (LSN).
    •Fosfatasa alcalina > 2,5 x LSN o fosfatasa alcalina > 5 x LSN en presencia de metástasis óseas o hepáticas.
    •Bilirrubina total > 1,5 x LSN
    •Aclaramiento de creatinina calculado < 50 ml/min.
    •Hipercalcemia (calcio sérico >=12,0 mg/dl o sintomática).
    Medicaciones
    •Quimioterapia previa, (excepto quimioterapia adyuvante, siempre que la última dosis de terapia adyuvante se haya recibido al menos un año antes de la inclusión), hormonoterapia, radioterapia (excepto radioterapia paliativa para las metástasis óseas o radioterapia para las metástasis del SNC) o inmunoterapia para el tratamiento del CPCNP avanzado.
    •Tratamiento farmacológico o terapia previa con agentes en investigación para el CPCNP.
    •Tratamiento anticoagulante terapéutico. Se permite la anticoagulación profiláctica de los dispositivos de acceso venoso (es decir, con dosis bajas de warfarina (1-2 mg/día) o dosis bajas de heparina) siempre que el INR <=1,2 y el TTP sea ≤ 1,2 y el TTP sea ≤ LSN dentro de 1 semana antes a la aleatorización.
    •Tratamiento diario crónico con aspirina (> 325 mg/día) o con agentes antiinflamatorios no esteroideos conocidos por su inhibición de la función plaquetaria. También se permite el tratamiento con dipiridamol, ticlopidina, clopidogrel y/o cilostazol.
    Generales
    •El sujeto ha participando en ensayos clínicos o se ha sometido a otros procedimientos de investigación dentro de los 30 días previos a la inclusión en el estudio.
    •El sujeto tiene un embarazo evidente (p. ej., prueba de HCG sérica positiva) o se encuentra en periodo de lactancia.
    •Mujer u hombre con pareja en edad fértil que no esté de acuerdo con tomar precauciones anticonceptivas adecuadas, es decir, utilizar métodos anticonceptivos de barrera doble (p. ej., diafragma más condón) o abstinencia durante el transcurso del estudio y durante los 6 meses siguientes a la última administración del fármaco en estudio para las mujeres y 1 mes para los hombres.
    •El sujeto presenta una sensibilidad conocida a alguno de los productos que se administrarán durante el estudio.
    E.5 End points
    E.5.1Primary end point(s)
    Fase 1b
    •Incidencia de TLD.
    •Incidencia y gravedad de los acontecimientos adversos

    Fase 2
    •Tasa de respuesta objetiva (respuesta completa o parcial)
    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 Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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) Yes
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    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 Information not present in EudraCT
    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
    El final del estudio se definirá como la fecha en que el último sujeto realice la visita final de seguimiento de la seguridad (aproximadamente 4 semanas después de la dosis final de AMG951).
    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 months10
    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 months10
    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 Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    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 state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 224
    F.4.2.2In the whole clinical trial 224
    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 Decision2007-12-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2007-10-09
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2011-11-14
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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