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   37736   clinical trials with a EudraCT protocol, of which   6184   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:2011-003308-18
    Sponsor's Protocol Code Number:MO27782
    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:2011-11-08
    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 number2011-003308-18
    A.3Full title of the trial
    A two-cohort, open-label, multicenter Phase II trial assessing the efficacy and safety of pertuzumab given in combination with trastuzumab and vinorelbine in first line patients with HER2-positive advanced (metastatic or locally advanced) breast cancer.
    Ensayo fase II multicentrico, abierto, de dos cohortes para determinar la eficacia y seguridad de pertuzumab en combinación con trastuzumab y vinorelbine en pacientes de primera línea de cáncer de mama avanzado (localmente avanzado o metastasico) HER-2 positivo.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Randomized Phase II study of pertuzumab, trastuzumab and vinorelbine in patients with HER2-positive breast cancer.
    Ensayo fase II randomizado de pertuzumab, trastuzumab, vinorelbina en pacientes con cáncer de mama avanzado HER-2 positivo.
    A.3.2Name or abbreviated title of the trial where available
    VELVET
    VELVET
    A.4.1Sponsor's protocol code numberMO27782
    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 SponsorF. Hoffmann-La Roche Ltd.
    B.1.3.4CountrySwitzerland
    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 supportF. Hoffmann-La Roche Ltd.
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationF. Hoffmann-La Roche Ltd.
    B.5.2Functional name of contact pointTrial Information Support Line-TISL
    B.5.3 Address:
    B.5.3.1Street AddressGrenzacherstrasse 124
    B.5.3.2Town/ cityBasel
    B.5.3.3Post code4070
    B.5.3.4CountrySwitzerland
    B.5.4Telephone numbernananana
    B.5.5Fax numbernananana
    B.5.6E-mailglobal.rochegenentechtrials@roche.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 namePertuzumab (rhuMAb 2C4)
    D.3.2Product code RO 4368451/F01
    D.3.4Pharmaceutical form 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 INNPertuzumab
    D.3.9.1CAS number 380610-27-5
    D.3.9.2Current sponsor codeRO4368451
    D.3.9.3Other descriptive namerhuMAb 2C4
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product 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.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Bendarelbin
    D.2.1.1.2Name of the Marketing Authorisation holderBendalis GmbH
    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 nameVinorelbine
    D.3.4Pharmaceutical form 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 INNVINORELBINE
    D.3.9.1CAS number 71486-22-1
    D.3.9.4EV Substance CodeSUB00069MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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.IMP: 3
    D.1.2 and D.1.3IMP RoleComparator
    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 Herceptin
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Ltd., UK
    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.3.4Pharmaceutical form Powder for concentrate for solution for injection/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 INNTRASTUZUMAB
    D.3.9.1CAS number 180288-69-1
    D.3.9.2Current sponsor codeRO 45-2317
    D.3.9.4EV Substance CodeSUB12612MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product 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
    HER2-positive advanced (metastatic or locally advanced) breast cancer
    Cáncer de mama avanzado (metastásico o localmente avanzado) HER-positivo.
    E.1.1.1Medical condition in easily understood language
    HER2-positive advanced breast cancer
    Cáncer de mama avanzado HER-positivo.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.0
    E.1.2Level LLT
    E.1.2Classification code 10065430
    E.1.2Term HER-2 positive breast 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 compare objective overall response rates (ORR) assessed
    by a blinded independent review committee (IRC) of pertuzumab given in combination with trastuzumab and vinorelbine together in a single infusion bag versus conventional sequential administration in separate infusion bags.
    Comparar los índices de respuesta objetiva global (RG), evaluados de forma ciega por un comité de revisión independiente (CRI), de pertuzumab administrado en combinación con trastuzumab en una misma bolsa de infusión, seguido de vinorelbina, frente a la administración secuencial convencional en distintas bolsas de infusión.
    E.2.2Secondary objectives of the trial
    o ORR assessed by the investigator
    o Time to response assessed by IRC and investigator
    o Duration of response assessed by IRC and investigator
    o Progression free survival (PFS)
    o Time to progression (TTP)
    o Overall survival (OS)
    o Safety and tolerability
    o Quality of life (EQ-5D and FACT-B questionnaires)
    RG evaluado por el investigador
    Tiempo hasta la respuesta evaluado por el CRI y el investigador
    Duración de la respuesta evaluada por el CRI y el investigador
    Supervivencia libre de progresión (SLP)
    Tiempo hasta la progresión (TP)
    Supervivencia global (SG)
    Seguridad y tolerancia
    Calidad de vida (Cuestionarios EQ-5D y FACT-B)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed written informed consent approved by the relevant Institutional Ethical Review Board (IRB).
    2. Female or male patients aged 18 years or older.
    3. Histologically or cytologically confirmed and documented adenocarcinoma of the breast with metastatic or locally advanced disease not amenable to curative resection.
    4. HER2-positive (defined as either immunohistochemistry
    [IHC] 3+ or in situ hybridization [ISH] positive) as assessed by local laboratory on primary or metastatic tumor (ISH positivity is defined as a ratio of 2.0 or greater for the number of HER2 gene copies to the number of signals for CEP17, or for single probe tests, a HER2 gene count greater than 4).
    5. At least one measurable lesion and/or non-measurable
    disease evaluable according to Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1 (Eisenhauer et al. 2009).
    6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
    7. Left ventricular ejection fraction (LVEF) of at least 55%.
    8. Negative pregnancy test in women of childbearing potential (premenopausal or less than 12 months of amenorrhea post-menopause, and who have not undergone surgical sterilization).
    9. For women of childbearing potential who are sexually active, agreement to use a highly effective, nonhormonal form of contraception or two effective forms of non-hormonal contraception during and for at least 6 months post-study treatment.
    10. Fertile males willing and able to use effective nonhormonal
    means of contraception (barrier method of contraception in conjunction with spermicidal jelly, or surgical sterilization) during and for at least 6 months post-study treatment.
    11. Life expectancy of at least 12 weeks.
    Firmar el consentimiento informado por escrito aprobado por el Comité Ético de Investigación Clínica
    Varones o mujeres ? 18 años.
    Presentar adenocarcinoma de mama confirmado histológica o citológicamente y documentado, con enfermedad metastásica o localmente avanzada que no se pueda tratar con resección con intención curativa.
    Estado HER2 positivo (que se define como una puntuación 3+ en inmunohistoquímica [IHC]o positividad en hibridación in situ [ISH]), determinado en el laboratorio local en el tumor primario o en una lesión metastásica (la positividad en ISH se define como una relación ? 2,0 del número de copias del gen HER2 al número de señales en CEP17, o en las pruebas en las que se emplea una sola sonda, un recuento del gen HER2 superior a 4).
    Presentar, al menos, una lesión medible y/o enfermedad no medible que sea evaluable de acuerdo con los Criterios de Evaluación de la Respuesta en Tumores Sólidos (RECIST), versión 1.1 (Eisenhauer et al. 2009).
    Estado funcional del Eastern Cooperative Oncology Group (ECOG) 0 o 1.
    Fracción de eyección ventricular izquierda (FEVI) de al menos 55%.
    Las mujeres potencialmente fértiles (aquellas que sean premenopáusicas o postmenopáusicas con amenorrea desde hace menos de 12 meses y que no estén esterilizadas quirúrgicamente) deben presentar un resultado negativo en la prueba de embarazo
    Las mujeres potencialmente fértiles que sean sexualmente activas deben comprometerse a utilizar un método anticonceptivo no hormonal altamente eficaz o dos métodos anticonceptivos no hormonales eficaces durante el tratamiento del estudio y como mínimo hasta 6 meses después de su terminación.
    Los varones fértiles deben estar dispuestos y ser capaces de utilizar métodos anticonceptivos no hormonales eficaces (un método anticonceptivo de barrera conjuntamente con gel espermicida o esterilización quirúrgica) durante el tratamiento del estudio y como mínimo hasta 6 meses después de su terminación.
    Esperanza de vida de 12 semanas, como mínimo.
    E.4Principal exclusion criteria
    1. Previous systemic non-hormonal anticancer therapy in the
    metastatic or locally advanced breast cancer setting.
    2. Previous approved or investigative anti-HER2 agents in any breast cancer treatment setting, except trastuzumab and/or
    lapatinib in the adjuvant or neoadjuvant setting.
    3. Disease progression while receiving trastuzumab and/or
    lapatinib in the adjuvant or neoadjuvant setting.
    4. Disease-free interval from completion of adjuvant or neo-adjuvant systemic non-hormonal treatment to recurrent disease of less than 6 months.
    5. History of persistent Grade 2 or higher (NCI-CTC, Version
    4.0) hematological toxicity resulting from previous adjuvant
    or neoadjuvant therapy.
    6. Radiographic evidence of central nervous system (CNS) metastases as assessed by computed tomography (CT) or
    magnetic resonance imaging (MRI).
    7. Current peripheral neuropathy of Grade 3 or greater
    (NCI-CTC, Version 4.0).
    8. History of other malignancy within the last 5 years, except
    for carcinoma in situ of the cervix or basal cell carcinoma.
    9. Serious uncontrolled concomitant disease that would
    contraindicate the use of any of the investigational drugs
    used in this study or that would put the patient at high risk for
    treatment-related complications.
    10. Inadequate organ function, evidenced by the following laboratory results:
    ? Absolute neutrophil count <1,500 cells/mm3
    ? Platelet count <100,000 cells/mm3
    ? Hemoglobin <9 g/dL
    ? Total bilirubin greater than upper limit of normal (ULN) (unless the patient has documented Gilbert?s syndrome)
    ? Aspartate aminotransferase AST; SGOT) or alanine aminotransferase (ALT; SGPT) >2.5 × ULN
    ? AST (SGOT) or ALT (SGPT) >1.5 × ULN with concurrent serum alkaline phosphatase >2.5 × ULN; Serum alkaline phosphatase may be >2.5 × ULN only if bone metastases are present and AST
    (SGOT) and ALT (SGPT) <1.5 × ULN
    ? Serum creatinine >2.0 mg/dL or 177 ?mol/L
    ? International normalized ratio (INR) and activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) >1.5 × ULN (unless on therapeutic coagulation)
    11. Uncontrolled hypertension (systolic >150 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident (CVA)/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) Grade II or higher, or serious cardiac arrhythmia requiring medication.
    12. Current known infection with HIV, HBV, or HCV.
    13. Dyspnea at rest due to complications of advanced malignancy, or other disease requiring continuous oxygen therapy.
    14. Major surgical procedure or significant traumatic injury within 28 days prior to enrollment into the study or anticipation of need for major surgery during the course of study treatment.
    15. Receipt of intravenous (IV) antibiotics for infection within 14 days prior to enrollment into the study.
    16. Current chronic daily treatment with corticosteroids (dose
    equivalent to or greater than 10 mg/day methylprednisolone),
    excluding inhaled steroids.
    17. Known hypersensitivity to any of the study medications or to
    excipients of recombinant human or humanized antibodies.
    18. History of receiving any investigational treatment within 28 days prior to enrollment into the study.
    19. Concurrent participation in any clinical trial.
    20. Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
    1. Administración previa de terapia anticancerosa no hormonal sistémica en el entorno del cáncer de mama metastásico o localmente avanzado.
    2. Administración previa de agentes anti-HER2 aprobados o en investigación, en cualquier entorno del tratamiento del cáncer de mama, exceptuando trastuzumab y/o lapatinib utilizados en el entorno neoadyuvante o adyuvante.
    3. Progresión de la enfermedad durante el tratamiento con trastuzumab y/o lapatinib en el entorno adyuvante o neoadyuvante
    4. Intervalo libre de enfermedad de menos de 6 meses desde la terminación del tratamiento no hormonal sistémico adyuvante o neoadyuvante hasta la recurrencia de la enfermedad.
    5. Antecedentes de toxicidad hematológica de grado ?2 (NCI-CTC, Versión 4.0) persistente a consecuencia del tratamiento previo adyuvante o neoadyuvante.
    6. Evidencia radiográfica de metástasis del sistema nervioso central (SNC), determinada en tomografía computerizada (TAC) o resonancia magnética (RM).
    7. Neuropatía periférica de grado ?3 (NCI CTC, Versión 4.0) en la actualidad.
    8. Antecedentes de otras neoplasias en los 5 últimos años, exceptuando carcinoma in situ de cérvix o carcinoma basocelular.
    9. Enfermedad concomitante grave, no controlada, para la cual estaría contraindicado el uso de cualquiera de los fármacos en investigación utilizados en este estudio o que implicaría para el paciente un riesgo alto de complicaciones relacionadas con el tratamiento.
    10. Función de órganos inadecuada, evidenciada por los resultados de laboratorio siguientes:
    ? Recuento absoluto de neutrófilos <1500 células/mm3.
    ? Recuento de plaquetas <100.000 células/mm3.
    ? Hemoglobina <9 g/dl.
    ? Bilirrubina total por encima del límite superior de normalidad (LSN) (a menos que el paciente presente síndrome de Gilbert documentado).
    ? Aspartato aminotransferasa (AST; SGOT) o alanina aminotransferasa (ALT; SGPT) >2,5 × LSN.
    ? AST (SGOT) o ALT (SGPT) >1,5 × LSN acompañado de concentraciones de fosfatasa alcalina sérica >2,5 × LSN. La concentración de fosfatasa alcalina sérica puede ser >2,5 × LSN sólo en el caso de que el paciente presente metástasis óseas y los valores de AST (SGOT) y ALT (SGPT) sean <1,5 × LSN.
    ? Creatinina sérica >2,0 mg/dl o 177 ?mol/l.
    ? Índice internacional normalizado (INR) y tiempo de tromboplastina parcial activada (TTPa) o tiempo de tromboplastina parcial (TPP) >1,5 × LSN (a menos que el paciente esté recibiendo tratamiento anticoagulante).
    11. Hipertensión no controlada (sistólica >150 mm Hg y/o diastólica >100 mm Hg) o enfermedad cardiovascular clínicamente significativa (es decir, activa): accidente cerebrovascular (ACV)/ictus o infarto de miocardio en los 6 meses previos a la administración de la primera dosis de la medicación del estudio, angina de pecho inestable, insuficiencia cardíaca congestiva (ICC) de grado ? II de la New York Heart Association (NYHA) o arritmias cardíacas graves que requieran medicación.
    12. Infección confirmada por VIH, VHB o VHC en la actualidad.
    13. Disnea en reposo debida a complicaciones de la enfermedad neoplásica avanzada u otras enfermedades que requieran oxigenoterapia continua.
    14. Pacientes sometidos a procedimientos de cirugía mayor o que hayan sufrido traumatismos significativos en los 28 días previos a la inclusión en el estudio o que previsiblemente deban someterse a un procedimiento de cirugía mayor en el transcurso del tratamiento del estudio.
    15. Administración de antibióticos intravenosos (IV) para el tratamiento de infecciones en los 14 días previos a la inclusión en el estudio
    16. Tratamiento crónico diario con corticosteroides en la actualidad (con una dosis equivalente o superior a >10 mg/día de metilprednisolona), exceptuando esteroides administrados por vía inhalatoria.
    17. Hipersensibilidad confirmada a cualquiera de las medicaciones del estudio o a los excipientes de los anticuerpos recombinantes humanos o humanizados.
    18. Tratamiento con cualquier fármaco en investigación en los 28 días previos a la inclusión en el estudio.
    19. Participación simultánea en cualquier ensayo clínico.
    20. Pacientes que, en opinión del investigador, sean incapaces o no estén dispuestos a cumplir los requisitos del protocolo.
    E.5 End points
    E.5.1Primary end point(s)
    ORR assessed by IRC according to RECIST version 1.1, based on the best (confirmed) overall response (BOR; defined as the best response recorded from the start of trial treatment until disease
    progression/recurrence or death).
    La variable principal de eficacia en un paciente es la RG evaluada por el CRI de acuerdo con los criterios RECIST versión 1.1, basándose en la mejor respuesta global (confirmada) (MRG; que se define como la mejor respuesta registrada desde el inicio del tratamiento del estudio hasta que se manifiesta progresión/recurrencia de la enfermedad o se produce la muerte del paciente).
    E.5.1.1Timepoint(s) of evaluation of this end point
    When all patients have progressed, have been followed up for at least 24 months after the last patient is enrolled into the corresponding cohort, discontinued study medication, withdrawn consent from the study, or died, whichever occurs first.
    Cuando todos los pacientes hayan manifestado progresión de la enfermedad, se les haya realizado un seguimiento, como mínimo, hasta 24 meses después de la inclusión del último paciente en la cohorte correspondiente, hayan terminado prematuramente el tratamiento con la medicación del estudio, retirado su consentimiento para continuar en el estudio o hayan fallecido, dependiendo de lo que ocurra primero
    E.5.2Secondary end point(s)
    ? BOR as assessed by the investigator
    ? Time to and duration of response (in responders) as assessed by the Investigator
    and IRC
    ? PFS
    ? TTP
    ? OS
    ? MRG evaluada por el investigador
    ? Tiempo hasta la respuesta y duración de la respuesta (en los pacientes con respuesta), evaluados por el investigador y el CRI
    ? SLP
    ? TP
    ? SG
    E.5.2.1Timepoint(s) of evaluation of this end point
    Final analysis of PFS and TTP, and the first analysis of OS will be performed at the time of the final analysis of BOR.
    The final analysis of OS will take place when all patients have been followed up for at least 24 months after the last patient is enrolled into the corresponding cohort, unless they have been lost to follow-up, withdrawn consent, or died, or if the study is prematurely terminated by the Sponsor, whichever occurs first.
    El análisis final de la SLP y el TP y el primer análisis de la SG se realizarán en el momento del análisis final de la MRG.
    El análisis final de la SG se realizará cuando se haya realizado un seguimiento de todos los pacientes, como mínimo, hasta 24 meses después de la inclusión del último paciente en la cohorte correspondiente, a menos que se haya perdido el seguimiento de los pacientes o que éstos hayan retirado su consentimiento o fallecido, o que el promotor decida terminar prematuramente el estudio, dependiendo de lo que ocurra primero.
    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 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
    Quality of life, tolerability, optional translational research
    Calidad de vida, tolerabilidad, investigación translacional opcional
    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.8.2.4Number of treatment arms in the trial2
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA57
    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
    Brazil
    European Union
    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
    The study will end when all patients have been followed up for at least 24 months after the last patient is enrolled into the corresponding cohort, unless they have been lost to follow-up, withdrawn consent, or died, or if the study is prematurely terminated by the Sponsor, whichever occurs first.
    El estudio terminará cuando se haya realizado un seguimiento de todos los pacientes, como mínimo, hasta 24 meses después de la inclusión del último paciente en la cohorte correspondiente, a menos que se haya perdido el seguimiento de los pacientes o que éstos hayan retirado su consentimiento o fallecido o que el promotor decida terminar prematuramente el estudio, dependiendo de lo que ocurra primero.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    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 years2
    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: 100
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 110
    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 state35
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 161
    F.4.2.2In the whole clinical trial 210
    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)
    Patients who discontinue study treatment for progressive disease or other reasons will receive treatment according to the local standard of care. Any post-study anticancer therapies, information on patient outcomes, and information on post-progression anticancer therapies will be recorded in the eCRF during the study follow-up period as reasonably possible
    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 Decision2012-01-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-12-29
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-10-15
    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
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA