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    Summary
    EudraCT Number:2012-002018-37
    Sponsor's Protocol Code Number:BO27938
    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:2013-04-09
    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 number2012-002018-37
    A.3Full title of the trial
    A RANDOMIZED, MULTICENTER, OPEN LABEL PHASE III STUDY TO EVALUATE THE EFFICACY AND SAFETY OF TRASTUZUMAB EMTANSINE VERSUS TRASTUZUMAB AS ADJUVANT THERAPY FOR PATIENTS WITH HER2-POSITIVE PRIMARY BREAST CANCER WHO HAVE RESIDUAL TUMOR PRESENT PATHOLOGICALLY IN THE BREAST OR AXILLARY LYMPH NODES FOLLOWING PREOPERATIVE THERAPY.
    ESTUDIO DE FASE III, ABIERTO, MULTICÉNTRICO, ALEATORIZADO PARA EVALUAR LA EFICACIA Y SEGURIDAD DE TRASTUZUMAB EMTANSINE VERSUS TRASTUZUMAB COMO TRATAMIENTO ADYUVANTE EN PACIENTES CON CÁNCER DE MAMA PRIMARIO HER2-POSITIVO CON PRESENCIA PATOLÓGICA DE TUMOR RESIDUAL EN LA MAMA O NÓDULO LINFÁTICO AXILAR TRAS TRATAMIENTO PREOPERATORIO
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase III, randomized, multicenter, multinational, open label study in patients with HER2-positive primary breast cancer following neoadjuvant chemotherapy and surgery.
    Estudio de fase III, abierto, multicéntrico, internacional, aleatorizado en pacientes con cáncer de mama primario HER2-positivo seguido de quimioterapia neoadjuvante y cirugía.
    A.4.1Sponsor's protocol code numberBO27938
    A.5.4Other Identifiers
    Name:National Surgical Adjuvant Breast & Bowel ProjectNumber:NSABP B-50-I
    Name:German Breast GroupNumber:GBG 77
    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.5.6E-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 nametrastuzumab emtansine (T-DM1)
    D.3.2Product code RO5304020/F02
    D.3.4Pharmaceutical form Powder for concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNtrastuzumab emtansine
    D.3.9.1CAS number 1018448-65-1
    D.3.9.2Current sponsor codeRO5304020
    D.3.9.3Other descriptive nameT-DM1, Trastuzumab-MCC-DM1
    D.3.9.4EV Substance CodeSUB35467
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number160
    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.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 Yes
    D.3.11.13.1Other medicinal product typeConjugado anticuerpo-fármaco (ADC) compuesto por un anticuerpo monoclonal humanizado (trastuzumab) y DM1.
    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 Herceptin®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration Limited
    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 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 codeRO0452317
    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 primary breast cancer.
    Cáncer de mama primario HER2-positivo.
    E.1.1.1Medical condition in easily understood language
    HER2-positive primary breast cancer.
    Cáncer de mama primario HER2-positivo.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10065430
    E.1.2Term HER-2 positive breast cancer
    E.1.2System Organ Class 100000004864
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10027475
    E.1.2Term Metastatic breast cancer
    E.1.2System Organ Class 100000004864
    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 the length of time it takes for the primary breast cancer to recur after treatment with preoperative chemotherapy followed by surgery between the 2 treatment arms.
    Comparar entre los dos grupos de tratamiento, el tiempo del intervalo sin recidivas de cáncer de mama primario tras el tratamiento preoperatorio con quimioterapia seguido de cirugía.
    E.2.2Secondary objectives of the trial
    To compare the length of time it takes for:
    ? the primary breast cancer to develop in other location(s)
    ? occurrence of secondary cancers in other organs
    ? death
    To compare side effects of the study medication between the 2 treatment arms.
    Comparar el tiempo del intervalo en el que:
    -Se desarrolla cáncer de mama primario en otras localización(es)
    -Aparecen cánceres secundarios en otros órganos
    -Se produce la muerte
    Comparar las reacciones adversas de la medicación del ensayo entre los 2 grupos de tratamiento.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    ? Adult patients, aged at least 18 years
    ? Histologically confirmed invasive breast cancer with clinical staging T1-4, N0-3, M0 (no metastasis)
    ? HER2-positive tumor as confirmed by central laboratory HER2 testing (immunohistochemistry and/or in-situ hybridization)
    ? Patients must have received at least 6 cycles with 16 weeks of prior chemotherapy in the preoperative (neoadjuvant) setting including at least 9 weeks of a taxane and 9 weeks of HER2-directed therapy which may be given concurrently
    ? Surgical removal of all clinically-evident disease in the breast and lymph nodes
    ? Pathologic evidence of residual invasive cancer following completion of preoperative chemotherapy
    ? ECOG performance status of 0 or 1
    ? Life expectancy of at least 6 months from the first dose of study treatment
    ? Adequate organ function as determined by the following laboratory results, within 14 days prior to randomization.
    1. Edad ? 18 años.
    2.Carcinoma de mama invasivo confirmado por medios histológicos con estadio clínico: T1 a T4, N0 a N3, M0 (no metástasis)
    3.Tumor HER2-positivo confirmado por un laboratorio central que analiza HER2 (inmunohistoquímica y/o hibridación in situ)
    4. Las pacientes deben haber recibido al menos 6 ciclos de tratamiento preoperatorio con quimioterapia (neoadyuvancia) hasta 16 semanas incluyendo como mínimo 9 semanas con un taxano y 9 semanas de tratamiento dirigido contra el HER2, los cuales pueden administrarse simultáneamente.
    5. Extirpación quirúrgica de toda la enfermedad clínicamente evidente de la mama y los ganglios linfáticos.
    6. Hallazgos histopatológicos de carcinoma residual invasivo una vez finalizado el tratamiento preoperatorio.
    7. Estado funcional del ECOG de 0 o 1.
    8. Esperanza de vida de igual o superior a seis meses.
    9. Función orgánica adecuada determinada por los siguientes valores de laboratorio, dentro de los 14 días previos a la aleatorización.
    E.4Principal exclusion criteria
    ? Metastatic breast cancer
    ? History of any prior breast cancer except for lobular carcinoma in situ
    ? Treatment with a cumulative dose of epirubicin greater than 480mg/m2 or any other anthracycline like doxirubicin greater than 240mg/m2
    ? Treatment with any investigational anticancer drug within 28 days prior to commencing study treatment
    ? History of other malignancy within the previous 5 years except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or other malignancies with an expected curative outcome
    ? Peripheral neuropathy greater or equal to Grade 2
    ? Uncontrolled cardiopulmonary dysfunction (e.g., high blood pressure, angina, serious cardiac arrhythmia)
    ? Myocardial infarction within 12 months prior to randomization
    ? Active liver disease like hepatitis
    ? Other current, severe, uncontrolled systemic disease (e.g., clinically significant metabolic disease, wound healing disorders, ulcers)
    ? For female patients, current pregnancy or lactation
    ? Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment
    ? Currrent, serious, uncontrolled Infections or known infection with HIV.
    ?Cáncer de mama metastásico.
    ?Antecedentes de cualquier cáncer de mama previo, excepto CLIS.
    ?Tratamiento con una dosis acumulada de epirubicina más de 480 mg/m2 o otra antraciclina como doxorrubicina más de 240 mg/m2.
    ?Tratamiento con cualquier antineoplásico en investigación en los 28 días previos al comienzo del tratamiento del estudio.
    ?Antecedentes de otro tumor maligno en los últimos cinco años, con la excepción del CIS del cuello uterino tratado correctamente, el carcinoma cutáneo distinto del melanoma, el cáncer de útero en estadio I u otros cánceres distintos del de mama que tengan un desenlace similar al de los mencionados anteriormente.
    ?Neuropatía periférica de grado 2 o superior según los CTCAE del NCI (versión 4.0).
    ?Disfunción cardiopulmonar no controlada (por ejemplo, hipertensión, angina de pecho, grave arritmia cardíaca),
    ?Infarto dentro de los 12 meses previos a la aleatorización
    ?Enfermedad hepática activa como hepatitis.
    ?Otras enfermedades sistémicas, no controladas, graves y activas, por ejemplo, enfermedades metabólicas clínicamente significativas, trastornos de la cicatrización de las heridas; úlceras.
    ?En las mujeres, embarazo o lactancia actuales.
    ?Intervención de cirugía mayor sin relación con el cáncer de mama o traumatismo importante en los aproximadamente 28 días anteriores a la aleatorización, o necesidad prevista de cirugía mayor durante el tratamiento del estudio.
    ?Infecciones concomitantes graves y no controladas, o infección por el VIH.
    E.5 End points
    E.5.1Primary end point(s)
    Invasive disease-free survival (IDFS)
    Supervivencia sin enfermedad invasiva
    E.5.1.1Timepoint(s) of evaluation of this end point
    up to 10 years
    Hasta 10 años
    E.5.2Secondary end point(s)
    1. IDFS including second non-breast cancer
    2. Disease-free survival (DFS), including second non-breast cancer or contralateral or ipsilateral ductal carcinoma in situ
    3. Overall survival (OS)
    4. Recurrence-free interval (RFI): time between randomization and local, regional or distant breast cancer recurrence
    5. Distant recurrence-free interval (DRFI): time between randomization and distant breast cancer recurrence
    6. Cardiac and overall safety: Incidence of adverse events
    7. Quality of life: EORTC QLQ-C30, QLQ-BR23 and EQ-5D questionnaires.
    1.SSEI incluidos los segundos cánceres distintos del de mama
    2.Supervivencia sin enfermedad invasiva (SSEI), incluyendo segundos cánceres distintos del de mama o carcinoma homo o contralateral in situ
    3.Supervivencia global (SG)
    4.Intervalo sin recidivas: Tiempo desde la aleatorización hasta la recidiva a distancia del cáncer de mama.
    5.Intervalo sin recidivas a distancia (ISRD): tiempo desde la aleatorización hasta la recidiva a distancia del cáncer de mama.
    6.Seguridad cardíaca y seguridad global: Incidencia de acontecimientos adversos.
    7.Calidad de vida: cuestionarios QLQ-C30 de la EORTC, QLQ-BR23 y EQ-5D
    E.5.2.1Timepoint(s) of evaluation of this end point
    1 to 6. up to 13 years
    7. up to 3 years
    Del 1 al 6: hasta 13 años.
    7. Hasta 3 años.
    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 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
    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 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) 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 concerned11
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA125
    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
    Austria
    Belgium
    Brazil
    Canada
    China
    Colombia
    Czech Republic
    France
    Germany
    Greece
    Hong Kong
    Ireland
    Israel
    Italy
    Mexico
    Panama
    Peru
    Russian Federation
    Serbia
    South Africa
    Spain
    Sweden
    Switzerland
    Taiwan
    Turkey
    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 study will end after the last patient randomized into the study has undergone the last follow-up assessment. To enable long-term follow-up for survival and safety information, the last follow-up assessment is scheduled to occur 10 years after the first patient is randomized.
    El estudio finalizará después de que el último paciente aleatorizado en el estudio se haya sometido a la última evaluación de seguimiento. A fin de posibilitar el seguimiento a largo plazo para obtener información sobre la supervivencia y la seguridad, está previsto que la última evaluación de seguimiento tenga lugar diez años después de la aleatorización de la primera paciente.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years10
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years10
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 1200
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 284
    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 state65
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 688
    F.4.2.2In the whole clinical trial 1484
    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)
    Currently, Roche/Genentech does not have any plans to provide trastuzumab emtansine or other study interventions to patients after the conclusion of the study. However, patients who discontinue trastuzumab emtansine before the end of the 14 cycle treatment period, may complete the duration of their study therapy with trastuzumab if appropriate based on toxicity considerations.
    Actualmente Roche/Genentech no tiene intención de proporcionar trastuzumab emtansina o realizar otro ensayo intervencional con pacientes después de que el estudio finalice. Sin embargo, las pacientes que dejen de recibir trastuzumab emtansine antes de que termine el periodo de tratamiento con el ciclo 14 podrán completar la duración del tratamiento del estudio con trastuzumab, si se considera apropiado en base a la toxicidad.
    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 Decision2013-03-07
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-01-10
    P. End of Trial
    P.End of Trial StatusOngoing
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