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    Summary
    EudraCT Number:2010-024483-17
    Sponsor's Protocol Code Number:E7389-G000-309
    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:2011-09-15
    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 number2010-024483-17
    A.3Full title of the trial
    A Randomised, Open-label, Multicenter, Phase 3 Study to Compare the Efficacy and Safety of Eribulin with Dacarbazine in Subjects with Soft Tissue Sarcoma.
    Estudio de fase 3 multicéntrico, abierto y aleatorizado para comparar la eficacia y la seguridad de eribulina y dacarbazina en sujetos con sarcoma de tejidos blandos.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    "A Clinical Trial Comparing the Effectiveness and Safety of Eribulin and Dacarbazine for Treatment of Patients with Soft Tissue Sarcoma (A Type of Cancer)"
    "Un ensayo clínico que compara la eficacia y la seguridad de eribulina y dacarbazina en el tratamiento de pacientes con sarcoma de tejidos blandos (un tipo de cáncer)"
    A.4.1Sponsor's protocol code numberE7389-G000-309
    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 SponsorEisai Ltd
    B.1.3.4CountryUnited Kingdom
    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 supportEisai Ltd
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationEisai Ltd
    B.5.2Functional name of contact pointMedical Information Department
    B.5.3 Address:
    B.5.3.1Street AddressEuropean Knowledge Centre, Mosquito Way
    B.5.3.2Town/ cityHatfield, Herfordshire
    B.5.3.3Post codeAL10 9SN
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+44(0)800 001 4612
    B.5.5Fax number+44(0)845 676 1388
    B.5.6E-mailEUmedinfo@eisai.net
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Halaven
    D.2.1.1.2Name of the Marketing Authorisation holderEisai Ltd
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 Solution for injection
    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 INNEribulina
    D.3.9.2Current sponsor codeE7389
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.44
    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: 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 Detimedac 100mg
    D.2.1.1.2Name of the Marketing Authorisation holderMedac
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 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 INNDacarbazina
    D.3.9.1CAS number 4342-03-4
    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 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 Detimedac 200mg
    D.2.1.1.2Name of the Marketing Authorisation holderMedac
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 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 INNDacarbazina
    D.3.9.1CAS number 4342-03-4
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    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: 4
    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 Detimedac 500mg
    D.2.1.1.2Name of the Marketing Authorisation holderMedac
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 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 INNDacarbazina
    D.3.9.1CAS number 4342-03-4
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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
    Soft tissue sarcoma (STS)
    Sarcoma de tejidos blandos.
    E.1.1.1Medical condition in easily understood language
    Cancers of the supporting tissues of the body, including the muscles, nerves, fat, blood vessels and deep skin tissues
    Cánceres de los tejidos del cuerpo que dan apoyo, entre los que se incluyen los músculos, los nervios, la grasa, los vasos sanguíneos y los tejidos cutáneos profundos.
    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 HLGT
    E.1.2Classification code 10041299
    E.1.2Term Soft tissue sarcomas
    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 compare overall survival (OS) in subjects with advanced soft tissue sarcoma ([STS], one of two subtypes: adipocytic [ADI] or leiomyosarcoma [LMS]) when treated with eribulin (Arm A) or dacarbazine (Arm B).
    Comparar la supervivencia global (SG) en sujetos con sarcoma de tejidos blandos (STB) avanzado (uno de dos subtipos: adipocítico [ADI] o leiomiosarcoma [LMS]) tratados con eribulina (grupo A) o dacarbazina (grupo B).
    E.2.2Secondary objectives of the trial
    - To compare progression-free survival (PFS) between Arm A and Arm B.
    - To compare progression-free rate at Week 12 (PFR12wks) between Arm A and Arm B.
    - To compare the clinical benefit rate ([CBR], complete response (CR), partial response (PR) + durable stable disease ([dSD], duration of stable disease (SD) ? 11 weeks) between Arm A and Arm B.
    - To compare the safety and tolerability between Arm A and Arm B.
    - To characterize the population pharmacokinetics (PK) of eribulin in subjects with STS.
    - Comparar la supervivencia sin progresión (SSP) entre los grupos A y B.
    - Comparar la supervivencia sin progresión en la semana 12 (SSP12sem) entre los grupos A y B.
    - Comparar la tasa de beneficio clínico (TBC: respuesta completa [RC] + respuesta parcial [RP] + enfermedad estable duradera [EEd, duración de la enfermedad estable [EE] ? 11 semanas]) entre los grupos A y B.
    - Comparar la seguridad y la tolerabilidad entre los grupos A y B.
    - Caracterizar la farmacocinética (FC) poblacional de la eribulina en sujetos con STB.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Histologically confirmed diagnosis of soft tissue sarcoma of high or intermediate grade with one of the following histological subtypes:
    a. Adipocytic sarcoma, including:
    i. Dedifferentiated
    ii. Myxoid
    iii. Round Cell
    iv. Pleomorphic.
    b. Leiomyosarcoma.
    2. Documented evidence of advanced (locally recurrent, locally advanced and/or metastatic) adipocytic (restricted to subtypes listed in Inclusion 1) or leiomyosarcoma, incurable by surgery and/or radiotherapy.
    3. Subjects should have received standard therapies for advanced soft tissue sarcoma which must have included an anthracycline (unless contraindicated) with or without ifosfamide and then at least one additional regimen after failure of the anthracycline.
    4. Radiographic evidence of disease progression by RECIST criteria on or after the last anti-cancer therapy within the 6 months prior to randomization.
    5. Presence of measurable disease meeting the following criteria:
    a. At least one lesion of >= 1.0 cm in long-axis diameter for non lymph nodes or >= 1.5 cm in short-axis diameter for lymph nodes which is serially measurable according to RECIST 1.1 using either computerized tomography or magnetic resonance imaging or panoramic and close-up color photography.
    b. Lesions that have had radiotherapy must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
    6. Eastern Cooperative Oncology Group, performance status of 0, 1 or 2.
    7. Adequate renal function defined as calculated creatinine clearance > 50 mL/min per the Cockroft and Gault formula.
    8. Adequate bone marrow function, defined as:
    a. Absolute neutrophil count (ANC) >= 1,500/mm3 or >= 1.5 x 10[9]/L.
    b. Platelet count >= 100,000/mm3 or >= 100 x 10[9]/L.
    c. Hemoglobin (Hb) >= 10g/dL at baseline (blood transfusions, hematopoietic growth factors and hematinics are allowed during the Prerandomization Phase to correct Hb values < 10g/dL).
    9. Adequate liver function, defined as:
    a. Bilirubin <= 1.5 times the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome.
    b. Alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) <= 3 times ULN. For total ALP >3 times ULN, the ALP liver isoenzyme must be <= 3 times ULN.
    10. Female subjects of child-bearing potential must agree to use two forms of highly effective contraception from the last menstrual period prior to randomization (or use a double barrier method until they are on two forms of highly effective contraception for at least one menstrual cycle), during the study treatment, and for 3 months after the final dose of study treatment.
    11. Male subjects and their female partner who are of child-bearing potential (as defined in Inclusion 10), and are not practicing total abstinence, must agree to use two forms of highly effective contraception from the last menstrual period of their female partner prior to randomization (or use a double barrier method until they are on two forms of highly effective contraception for at least one menstrual cycle), during study treatment, and for 3 months (or 6 months if they received dacarbazine) after the final dose of study treatment.
    12. Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol.
    13. Males or females aged >= 18 years at the time of informed consent.
    1. Diagnóstico confirmado histológicamente de sarcoma de tejidos blandos de grado alto o intermedio con uno de los siguientes subtipos histológicos:
    a. Sarcoma adipocítico, que incluye los siguientes tipos:
    i.Indiferenciado
    ii.Mixoideo
    iii.De células redondas
    iv.Pleomorfo
    b. Leiomiosarcoma
    2. Indicios documentados de STB adipocítico (limitado a los subtipos indicados en el criterio de inclusión n.° 1) avanzado (localmente recidivante, localmente avanzado o metastásico) o leiomiosarcoma, incurable mediante cirugía, radioterapia o ambas.
    3. Los sujetos deben haber recibido tratamientos convencionales para el sarcoma de tejidos blandos avanzado que deben haber incluido una antraciclina (a menos que estén contraindicadas) con o sin ifosfamida y posteriormente al menos un régimen adicional tras el fracaso de la antraciclina.
    4. Signos radiográficos de progresión de la enfermedad conforme a los criterios RECIST con el último tratamiento antineoplásico o después de éste en los 6 meses previos a la aleatorización.
    5. Presencia de enfermedad mensurable que cumpla los siguientes criterios:
    a. Al menos una lesión > ó = 1,0 cm de diámetro longitudinal para localizaciones distintas de los ganglios linfáticos o > ó = 1,5 cm de diámetro transversal para los ganglios linfáticos mensurable de forma seriada conforme a los criterios RECIST 1.1 mediante tomografía computarizada, resonancia magnética o fotografía en color panorámica y de primer plano.
    b. Las lesiones que hayan recibido radioterapia deben mostrar signos de progresión de la enfermedad conforme a los criterios RECIST 1.1 para considerarse lesiones diana.
    6. Estado funcional del Eastern Cooperative Oncology Group (ECOG) de 0, 1 ó 2.
    7. Función renal adecuada definida como un aclaramiento de creatinina calculado > 50 ml/min según la fórmula de Cockroft y Gault.
    8. Función medular adecuada, definida como:
    a. Recuento absoluto de neutrófilos (RAN) > ó = 1.500/mm3 o > ó = 1,5 x 10^9/l.
    b. Recuento de plaquetas > ó = 100.000/mm3 (> ó = 100 x 10^9/l).
    c. Hemoglobina (Hb) > ó = 10 g/dl en el período basal (se permiten las transfusiones de sangre, los factores de crecimiento hematopoyéticos y los hematínicos durante la fase de prealeatorización para corregir valores de Hb < 10 g/dl).
    9. Función hepática adecuada, definida como:
    a. Bilirrubina < ó = 1,5 veces el límite superior de la normalidad (LSN) salvo para la hiperbilirrubinemia no conjugada del síndrome de Gilbert.
    b. Fosfatasa alcalina (FA), alanina-aminotransferasa (ALT) y aspartato-aminotransferasa (AST) < ó = 3 x LSN. Para valores de FA total > 3 x LSN, la concentración de la isoenzima hepática de la FA debe ser < ó = 3 x LSN.
    10. Las mujeres con capacidad reproductiva deben comprometerse a utilizar dos métodos anticonceptivos de alta eficacia a partir de la última menstruación antes de la aleatorización (o utilizar un método de doble barrera hasta que utilicen dos métodos anticonceptivos de alta eficacia durante al menos un ciclo menstrual), durante el tratamiento del estudio y durante 3 meses después de la dosis final del tratamiento del estudio.
    11. Los varones y sus parejas que tengan capacidad reproductiva (según se define en el criterio de inclusión n.° 10) y que no practiquen la abstinencia total deben comprometerse a utilizar dos métodos anticonceptivos de alta eficacia a partir de la última menstruación de la mujer antes de la aleatorización (o utilizar un método de doble barrera hasta que utilicen dos métodos anticonceptivos de alta eficacia durante al menos un ciclo menstrual), durante el tratamiento del estudio y durante 3 meses (ó 6 meses si han recibido dacarbazina) después de la última dosis del tratamiento del estudio.
    12. Aceptación voluntaria de otorgar el consentimiento informado por escrito y voluntad y capacidad para cumplir con todos los aspectos del protocolo.
    13. Sujetos de ambos sexos de edad > ó = 18 años en el momento del consentimiento informado.
    E.4Principal exclusion criteria
    1. Subjects who have received any anti-cancer therapy, including radiotherapy, cytotoxic, hormonal, biological (including humanized antibodies) and targeted agents within 21 days, or any investigational agent within 30 days, prior to randomization.
    2. Subjects who have not recovered from acute toxicities as a result of prior anti-cancer therapy to ? Grade 1, according to Common Terminology Criteria for Adverse Events (CTCAE), except for peripheral neuropathy (see Exclusion 6) and alopecia.
    3. Subjects that have previously been treated with dacarbazine or participated in a study with eribulin (whether treated with eribulin or not).
    4. Radiation therapy encompassing > 30% of bone marrow.
    5. Major surgery within 21 days prior to randomization.
    6. Pre-existing peripheral neuropathy > CTCAE Grade 2.
    7. Significant cardiovascular impairment, defined as:
    a. Cardiac failure > New York Heart Association (NYHA) Class II according to the NYHA Functional Classification,
    b. Unstable angina or myocardial infarction within 6 months of enrolment,
    c. Serious cardiac arrhythmia or cardiac arrhythmia
    requiring treatment.
    8. Subjects with a high probability of Long QT Syndrome.
    9. Subjects with known central nervous system metastases.
    10. Any serious concomitant illness or infection requiring treatment.
    11. Any malignancy that required treatment, or has shown evidence of recurrence (except for soft tissue sarcoma, non-melanoma skin cancer, or carcinoma in situ of the cervix) during the 5 years prior to randomization.
    12. Female subjects must not be pregnant as documented by a negative beta-human chorionic gonadotropin (ß-hCG) test with a minimum sensitivity 25 IU/L or equivalent unit of ß-hCG at Screening and Baseline, or breastfeeding.
    13. Hypersensitivity to either halichondrin A or halichondrin B chemical derivatives or both; or to dacarbazine, or to any of the dacarbazine excipients (please refer to the dacarbazine prescribing information).
    14. Any medical or other condition which, in the opinion of the PI or designee, will preclude participation in a clinical trial.
    1. Sujetos que hayan recibido cualquier tratamiento antineoplásico, incluida la radioterapia y agentes citotóxicos, hormonales, biológicos (incluidos los anticuerpos humanizados) y dirigidos en los 21 días previos a la aleatorización, o cualquier producto en investigación en los 30 días previos a la aleatorización.
    2. Sujetos con toxicidades agudas como consecuencia del tratamiento antineoplásico previo que no se hayan recuperado hasta un grado 1 conforme a los Criterios terminológicos comunes para acontecimientos adversos (CTCAE), excepto la neuropatía periférica (véase el criterio de exclusión n.° 6) y la alopecia.
    3. Sujetos que hayan recibido tratamiento previo con dacarbazina o que hayan participado en un estudio con eribulina (ya fueran tratados o no con eribulina).
    4. Radioterapia que cubra > 30 % de la médula ósea.
    5. Cirugía mayor en los 21 días previos a la aleatorización.
    6. Neuropatía periférica preexistente de grado > 2 según los CTCAE.
    7. Afectación cardiovascular
    significativa, definida como:
    a. Insuficiencia cardíaca de clase funcional > II de la New York Heart
    Association (NYHA).
    b. Angina inestable o infarto de miocardio en los 6 meses previos al
    reclutamiento.
    c. Arritmia cardíaca grave o que requiera tratamiento.
    8. Sujetos con una probabilidad elevada de sufrir un síndrome del QT largo.
    9. Sujetos con metástasis conocidas en el sistema nervioso central.
    10. Cualquier enfermedad o infección concomitante grave que requiera tratamiento.
    11. Cualquier neoplasia maligna que requiera tratamiento o que haya mostrado signos de recidiva (excepto el sarcoma de tejidos blandos, el cáncer de piel no melanomatoso o el carcinoma in situ del cuello uterino) en los 5 años previos a la aleatorización.
    12. Las mujeres no pueden estar embarazadas, situación que debe documentarse con una prueba de gonadotropina coriónica humana (subunidad beta, Beta-hCG) negativa con una sensibilidad mínima de 25 UI/l o unidades equivalentes de Beta-hCG en las visitas de selección y basal, ni pueden lactar.
    13. Hipersensibilidad a los derivados químicos de la halicondrina A o de la halicondrina B o ambos, a la dacarbazina o a alguno de los excipientes de la dacarbazina (véase la ficha técnica de la dacarbazina).
    14. Cualquier proceso médico o de otra naturaleza que, en opinión del IP o de la persona en quien delegue, impida la participación en un ensayo clínico.
    E.5 End points
    E.5.1Primary end point(s)
    Overall survival, measured from the date of randomization until date of death from any cause. Subjects who are lost to follow-up and the subjects who are alive at the date of data cut-off will be censored at the date the subject was last known alive.
    Supervivencia global, determinada desde la fecha de aleatorización hasta la fecha de la muerte por cualquier causa. Los sujetos con los que se haya perdido el contacto durante el seguimiento y los sujetos
    que estén vivos en la fecha de corte de los datos serán censurados en la última fecha en que se tenga conocimiento de que estaban vivos.
    E.5.1.1Timepoint(s) of evaluation of this end point
    When the target number of events (estimated to be 353 deaths) has been observed
    Cuando se haya observado el número esperado de acontecimientos (se calcula que serán 353 muertes).
    E.5.2Secondary end point(s)
    (1)Progression-free survival, defined as the time from the date of randomization to the date of first documentation of disease progression, or date of death (whichever occurs first). Progression free survival censoring rules will apply, and will be defined in the SAP.
    (2)Progression-free rate at Week 12, defined as the proportion of subjects alive and progression-free at 12 weeks from the date of randomization.
    (3)Clinical Benefit Rate, the proportion of subjects who have best overall response of CR + PR + dSD.
    (1) SSP, definida como el tiempo transcurrido desde la fecha de aleatorización hasta la fecha de la primera documentación de progresión de la enfermedad o la fecha de fallecimiento (lo que suceda en primer lugar). Se aplicarán reglas de censura de la SSP, que se definirán en el PAE.
    (2) TSP12sem, definida como la proporción de sujetos vivos y sin progresión 12 semanas después de la fecha de aleatorización.
    (3) TBC, definida como la proporción de sujetos con una mejor respuesta global de RC + RP + EEd.
    E.5.2.1Timepoint(s) of evaluation of this end point
    When the target number of events (estimated to be 353 deaths) has been observed
    Cuando se haya observado el número esperado de acontecimientos (se calcula que serán 353 muertes).
    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 No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Quality of Life
    Calidad de vida
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA60
    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
    Argentina
    Australia
    Austria
    Belgium
    Brazil
    Canada
    Chile
    Czech Republic
    Denmark
    France
    Germany
    India
    Israel
    Italy
    Korea, Republic of
    Netherlands
    New Zealand
    Poland
    Romania
    Russian Federation
    Singapore
    Spain
    Thailand
    United Kingdom
    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 end of the study will be when the last subject has died, unless the Sponsor decides to terminate survival follow-up for all subjects in the Extension Phase, once all subjects have discontinued study treatment.
    El final del estudio será cuando el ultimo paciente haya muerto, a menos que el promotor decida finalizar el seguimiento de supervivencia para todos los sujetos en la fase de extensión, una vez que todos los pacientes hayan discontinuado el tratamiento del estudio.
    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 months0
    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 months0
    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.1.1Number of subjects for this age range: 0
    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: 315
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 135
    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 200
    F.4.2.2In the whole clinical trial 450
    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)
    This is defined in the protocol
    Se define en el protocolo.
    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 Decision2011-05-19
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-05-06
    P. End of Trial
    P.End of Trial StatusOngoing
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