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   42891   clinical trials with a EudraCT protocol, of which   7066   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).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .

    Clinical Trials marked as "Trial now transitioned" were transitioned to the Clinical Trial Regulation 536/2014 and can be further followed in the Clinical Trial Information System  
     
    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:2016-003695-47
    Sponsor's Protocol Code Number:WO39391
    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:2018-04-09
    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 number2016-003695-47
    A.3Full title of the trial
    A PHASE III, MULTICENTER, RANDOMIZED, OPEN-LABEL STUDY COMPARING ATEZOLIZUMAB (ANTI-PD-L1 ANTIBODY)
    IN COMBINATION WITH ADJUVANT ANTHRACYCLINE/TAXANEBASED CHEMOTHERAPY VERSUS CHEMOTHERAPY ALONE IN PATIENTS WITH OPERABLE TRIPLE-NEGATIVE BREAST CANCER
    ESTUDIO EN FASE III, MULTICÉNTRICO, ALEATORIZADO Y ABIERTO PARA COMPARAR ATEZOLIZUMAB (ANTICUERPO ANTI-PD-L1) EN COMBINACIÓN CON QUIMIOTERAPIA ADYUVANTE BASADA EN ANTRACICLINA/taxano FRENTE A SOLO QUIMIOTERAPIA EN PACIENTES CON CÁNCER DE MAMA TRIPLE NEGATIVO OPERABLE
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Compare Atezolizumab (Anti-PD-L1 Antibody) in Combination With Adjuvant Anthracycline/Taxane based Chemotherapy Versus Chemotherapy Alone in Patients With Operable Triple-Negative Breast Cancer
    ESTUDIO PARA COMPARAR ATEZOLIZUMAB (ANTICUERPO ANTI-PD-L1) EN COMBINACIÓN CON QUIMIOTERAPIA ADYUVANTE BASADA EN ANTRACICLINA/taxano FRENTE A SOLO QUIMIOTERAPIA EN PACIENTES CON CÁNCER DE MAMA TRIPLE NEGATIVO OPERABLE
    A.4.1Sponsor's protocol code numberWO39391
    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. Hoffman-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 number+34913257300
    B.5.6E-mailspain.start_up_unit@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 nameAtezolizumab
    D.3.2Product code RO5541267/F03
    D.3.4Pharmaceutical form Solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNATEZOLIZUMAB
    D.3.9.1CAS number 1380723-44-3
    D.3.9.2Current sponsor codeRO5541267
    D.3.9.3Other descriptive nameMPDL3280A, Tecentriq
    D.3.9.4EV Substance CodeSUB178312
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    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 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 Paclitaxel
    D.2.1.1.2Name of the Marketing Authorisation holderActavis S.R.L.
    D.2.1.2Country which granted the Marketing AuthorisationRomania
    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 namepaclitaxel
    D.3.2Product code RO024-7506
    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 INNPACLITAXEL
    D.3.9.1CAS number 33069-62-4
    D.3.9.4EV Substance CodeSUB09583MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number0.3 to 1.2
    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 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 Doxorubicin
    D.2.1.1.2Name of the Marketing Authorisation holderActavis Group PTC
    D.2.1.2Country which granted the Marketing AuthorisationRomania
    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 nameDoxorubicin
    D.3.2Product code Ro 020-3296
    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 INNDOXORUBICIN HYDROCHLORIDE
    D.3.9.1CAS number 23214-92-8
    D.3.9.3Other descriptive nameDOXORUBICIN
    D.3.9.4EV Substance CodeSUB01827MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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 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 Cyclophosphamide
    D.2.1.1.2Name of the Marketing Authorisation holderBaxter Oncology GmbH
    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.3.1Product namecyclophosphamide
    D.3.2Product code Ro 004-2106
    D.3.4Pharmaceutical form Lyophilisate for 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 INNCYCLOPHOSPHAMIDE
    D.3.9.1CAS number 50-18-0
    D.3.9.3Other descriptive nameEndoxan
    D.3.9.4EV Substance CodeSUB06859MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    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: 5
    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 Epirubicin
    D.2.1.1.2Name of the Marketing Authorisation holderS.C. Actavis S.R.L.
    D.2.1.2Country which granted the Marketing AuthorisationRomania
    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 nameEpirubicin
    D.3.2Product code Ro 018-7742
    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 INNepirubicin
    D.3.9.1CAS number 56390-09-1
    D.3.9.3Other descriptive nameEPIRUBICIN HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB01915MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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
    Triple-negative breast cancer (TNBC)
    Cáncer de mama triple negative (CMTN)
    E.1.1.1Medical condition in easily understood language
    TNBC refers to a type of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PgR) or HER2/neu
    CMTN se refiere a un tipo de cáncer de mama que no expresa los genes para receptor de estrógeno (ER), receptor de progesterona (PgR) o HER2 / neu
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10006187
    E.1.2Term 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 evaluate the efficacy of adjuvant atezolizumab + paclitaxel, dose-dense doxorubicin/epirubicin, and cyclophosphamide (T-AC/EC) compared with T-AC/EC alone in patients with TNBC based on invasive disease-free survival (iDFS)
    •Evaluar la eficacia de atezolizumab adyuvante + paclitaxel, dosis densa de epirrubicina/doxorrubicina, y ciclofosfamida (T-AC/EC) en comparación con T-AC/EC en monoterapia en pacientes con CMTN basado en supervivencia libre de enfermedad invasiva(SLEi).
    E.2.2Secondary objectives of the trial
    • To evaluate the efficacy of adjuvant atezolizumab + T-AC/EC compared with T-AC/EC alone based on iDFS in the PD-L1 selected and in the node-positive disease subpopulations, overall survival (OS), recurrence-free interval (RFI), Distant RFI and disease-free survival (DFS)
    • To evaluate patient-reported outcomes (PROs) of function and health-related quality of life (HRQoL) associated with atezolizumab + T-AC/EC compared with T-AC/EC alone, as measured by the validated patient reported outcome tools
    • To evaluate the safety and tolerability of atezolizumab + T-AC/EC compared with T-AC/EC alone
    • To characterize the serum pharmacokinetics of atezolizumab when administered in combination with T-AC/ EC chemotherapy
    • To evaluate the immune response to atezolizumab
    • Evaluar la eficacia adjuvante de atezolizumab+T-AC/EC en comparación con T-AC/EC en monoterapia con base en SLEi en la subpoblación con expresión tumoral de PD-L1 seleccionada y en la subpoblación con afectación de ganglios linfáticos, supervivencia global (SG), intervalo libre de recidiva (ILR), ILR a distancia y supervivencia libre de enfermedad (SLE).
    • Evaluar los resultados recibidos por los pacientes (RCP) del funcionamiento y calidad de vida relacionada con la salud (CVRS) asociados con atezolizumab +T-AC/EC en comparación con T-AC/EC en monoterapia, determinados mediante las escalas funcionales validadas.
    • Evaluar la seguridad y la tolerabilidad de atezolizumab +T-AC/EC en comparación con T-AC/EC en monoterapia.
    • Caracterizar la farmacocinética sérica de atezolizumab cuando se administra en combinación con la quimioterapia con T-AC/EC.
    • Evaluar la respuesta inmunitaria a atezolizumab.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Age >= 18 years
    - Eastern Cooperative Oncology Group Performance Status of 0 or 1
    - Non-metastatic operable Stage II-III breast cancer; patients with node-negative disease must have a pathologic tumor size > 2cm
    - Histologically documented TNBC that is centrally confirmed
    - Confirmed tumor Programmed death-ligand 1 (PD-L1) evaluation (centrally conducted)
    - Adequately excised: Patients must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy
    - Pathological tumor-node-metastasis staging: Patient must have had sentinel lymph node biopsy and/or axillary lymph node dissection for evaluation of pathologic nodal status
    - Patients with synchronous bilateral invasive disease are eligible only if all bilateral invasive lesions are histologically confirmed as triple negative by central lab and have completed adequate pathological tumor-node metastasis staging bilaterally as described
    - No more than 8 weeks (56 days) may elapse between definitive breast surgery and randomization
    - Baseline left ventricular ejection fraction >= 53% measured by echocardiogram or multiple-gated acquisition scans
    - Adequate hematologic and end-organ function
    - Representative formalin-fixed, paraffin embedded tumor specimen from surgical resection in paraffin blocks or at least 25 unstained slides, with an associated pathology report documenting locally assessed ER, PgR, and HER2 negativity
    - For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab, or 6 months after the last dose of paclitaxel or doxorubicin, or 12 months after the last dose of cyclophosphamide
    - For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm during the treatment period and 6 months after the last dose of paclitaxel, cyclophosphamide, or doxorubicin/epirubicin
    - Women who are not postmenopausal or have not undergone a sterilization procedure must have a negative serum pregnancy test result within 14 days prior to initiation of study drug
    - Edad >= 18 años
    - Estado funcional del Grupo Oncológico Cooperativo del Este (ECOG) de 0 o 1
    - Cáncer de mama operable en estadio II-III no metastásico; pacientes sin afectación ganglionar deben tener un tamaño tumoral en el estudio anatomopatológico >=2 cm
    - CMTN histológicamente documentado que está centralmente confirmado
    - Evaluación confirmada de la expresión tumoral de PD-L1, documentada mediante el análisis central de una muestra representativa del tejido tumoral.
    - Con resección adecuada: los pacientes deben haberse sometido a una cirugía conservadora de la mama, una mastectomía, o una mastectomía con conservación del pezón o de la piel.
    - Estadificación anatomopatológica TNM (tumor, ganglios, metástasis): el paciente debe haberse sometido a una biopsia del ganglio linfático centinela (BGLC) o a una linfadenectomía axilar para la evaluación del estado anatomopatológico de los ganglios.
    - Pacientes con enfermedad invasiva bilateral sincrónica son aptos solo si todas las lesiones invasivas bilaterales son triple negativas, de acuerdo con la confirmación histológica del laboratorio central y cuentan con la debida estadificación anatomopatológica TNM bilateral, tal y como se ha descrito anteriormente.
    - No deben transcurrir más de 8 semanas (56 días) entre la intervención quirúrgica definitiva de la mama y la aleatorización.
    - FEVI inicial >=53 % determinada mediante ECO (preferiblemente) o MUGA.
    - Funciones hematológicas y orgánicas adecuadas.
    - Muestras tumorales representativas fijadas en formol e incluidas en parafina (FFPE) procedentes de la resección quirúrgica en bloques de parafina (preferentemente) o, como mínimo, 25 cortes sin teñir, con un informe de anatomopatología asociado que documente la negatividad de RE, RP y HER2 de acuerdo con la evaluación local.
    - Las mujeres con capacidad de concebir deben aceptar la abstinencia sexual (no mantener relaciones sexuales heterosexuales) o el uso de métodos anticonceptivos con una tasa anual de fallos < 1 % durante el período de tratamiento y, por lo menos, 5 meses después de la última dosis de atezolizumab, 6 meses después de la última dosis de paclitaxel o doxorrubicina, o 12 meses después de la última dosis de ciclofosfamida, lo que ocurra más tarde.
    - Los hombres: acuerdo para permanecer abstinente o usar medidas anticonceptivas y acuerdo para abstenerse de donar esperma durante el período de tratamiento y 6 meses después de la última dosis de paclitaxel, ciclofosfamida o doxorrubicina / epirrubicina
    - Las mujeres que no sean posmenopáusicas (amenorrea no inducida por el tratamiento durante un período 12 meses) o que no sean quirúrgicamente estériles deben tener un resultado negativo en la prueba de embarazo en suero en los 14 días previos al inicio del tratamiento con el fármaco del estudio.
    E.4Principal exclusion criteria
    - Prior history of invasive breast cancer
    - Any T4 clinical tumor
    - For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment planned in the context of this study
    - Previous therapy with anthracyclines or taxanes for any malignancy
    - History of ductal carcinoma in situ and/or lobular carcinoma in situ that was treated with any form of systemic, hormonal therapy, or radiotherapy (RT) to the ipsilateral breast where invasive cancer subsequently developed
    - Contraindication to RT when adjuvant RT is clinically indicated
    - Cardiopulmonary dysfunction
    - Prior malignancies within 5 years prior to randomization
    - History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
    - Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
    - Known allergy or hypersensitivity to any component of the atezolizumab, paclitaxel, cyclophosphamide, or doxorubicin/epirubicin formulations and filgrastim or pegfilgrastim or granulocyte-macrophage colony-stimulating factor formulations
    - Active or history of autoimmune disease or immune deficiency
    - History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
    - Positive HIV test at screening
    - Active hepatitis B, C virus infection and tuberculosis
    - Urinary outflow obstruction
    - Severe infections within 4 weeks prior to initiation of study treatment
    - Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
    - Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during the course of the study
    - Prior allogeneic stem cell or solid organ transplant
    - Administration of a live attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation of need for such a vaccine during the study or within 5 months after the last dose of atezolizumab
    - Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications
    - Prior treatment with CD137 agonists or immune checkpoint-blockade therapies
    - Treatment with systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressive medication during the study
    - Pregnant or lactating, or intending to become pregnant during the study
    - Antecedentes de cáncer de mama invasivo.
    - Cualquier tumor con estadio clínico T4
    - En el caso de cáncer de mama diagnosticado actualmente, cualquier tratamiento antineoplásico sistémico previo, aparte del previsto en el contexto de este estudio.
    - Tratamiento previo con antraciclinas o taxanos para cualquier tipo de neoplasia maligna.
    - Antecedentes de carcinoma ductal in situ y / o carcinoma lobulillar in situ que se trató con cualquier forma de terapia sistémica, hormonal o radioterapia (RT) en la mama ipsilateral donde posteriormente se desarrolló el cáncer invasive.
    - RT contraindicada si la RT adyuvante está clínicamente indicada.
    -Disfunción cardiopulmonary.
    - Neoplasias malignas previas en los 5 años anteriores a la aleatorización.
    - Antecedentes de reacciones alérgicas, anafilácticas u otras reacciones de hipersensibilidad a anticuerpos quiméricos o humanizados o a proteínas de fusión.
    - Hipersensibilidad conocida a los productos biofarmacéuticos producidos en células de ovario de hámster chino.
    - Alergia o hipersensibilidad conocida a cualquiera de los componentes de la formulación de atezolizumab, paclitaxel, ciclofosfamida o doxorrubicina/epirrubicina y a las formulaciones de filgrastim, pegfilgrastim o GM-CSF.
    - Enfermedad autoinmune o inmunodeficiencia, pasada o active.
    - Antecedentes de fibrosis pulmonar idiopática, neumonía organizativa, neumonitis inducida por fármacos, neumonitis idiopática o signos de neumonitis activa en la tomografía axial computarizada (TAC) de la selección.
    - Resultado positivo en la prueba de detección del VIH en la selección.
    - Infección activa por el virus de la hepatitis B, C y tuberculosis.
    - Obstrucción del flujo urinario.
    - Infecciones graves en las 4 semanas anteriores al inicio del tratamiento del estudio.
    - Tratamiento con antibióticos orales o intravenosos en las 2 semanas previas al inicio del tratamiento del estudio.
    - Intervención de cirugía mayor que no sea para fines diagnósticos en las 4 semanas anteriores al inicio del tratamiento del estudio o previsión de la necesidad de una intervención quirúrgica importante durante el studio
    - Alotrasplante de células madre o trasplante de víscera maciza.
    - Administración de una vacuna elaborada con virus atenuados en las 4 semanas anteriores al inicio del tratamiento del estudio o previsión de la necesidad de dicha vacuna durante el estudio o en los 5 meses posteriores a la última dosis de atezolizumab.
    - Cualquier otra enfermedad, disfunción metabólica o resultado en la exploración física o en los análisis clínicos que contraindique el uso de un fármaco en investigación, que pueda afectar a la interpretación de los resultados, o que ponga al paciente en gran riesgo de experimentar complicaciones del tratamiento.
    - Tratamiento previo con agonistas de CD137 o con inhibidores de puntos de control inmunitario.
    - Tratamiento con inmunosupresores sistémicos en las 2 semanas anteriores al inicio del tratamiento del estudio o previsión de la necesidad de administrar inmunosupresores sistémicos durante el estudio
    - Mujeres embarazadas, en período de lactancia o con intención de quedarse embarazadas durante el studio.
    E.5 End points
    E.5.1Primary end point(s)
    1. iDFS
    1. SLEi
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to 7 years
    Hasta 7 años
    E.5.2Secondary end point(s)
    1. iDFS in the subpopulation with PD-L1-selected tumor status (IC1/2/3) and node-positive disease
    2. OS
    3. iDFS including second primary non-breast invasive cancer as an event
    4. RFI
    5. Distant RFI
    6. DFS
    7. Occurrence and severity of adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
    8. Mean and mean changes from baseline score in function (role, physical) and global health status (GHS)/HRQoL by assessment timepoint, and between treatment arms as assessed by the functional and GHS/HRQoL scales of the EORTC QLQ-C30
    9. Serum concentration of atezolizumab at specified timepoints
    10. Incidence of anti-drug antibodies (ADAs) during the study relative to the prevalence of ADAs at baseline
    1. SLEi en la subpoblación con expresión tumoral de PD-L1 seleccionada (CI1/2/3)
    2. SG
    3. SLEi incluyendo el cancer primario no invasive de mama como un evento
    4. ILR
    5. ILR a distancia
    6. SLI
    7. Ocurrencia y gravedad de los eventos adversos definidos por los Criterios de terminología común del Instituto Nacional de Cáncer para eventos adversos versión 4.0
    8. Valor medio y media del cambio con respecto a la puntuación inicial del funcionamiento (físico, actividades cotidianas) y el EGS/CVRS en cada punto temporal de evaluación, y entre grupos de tratamiento, determinados mediante las escalas funcionales y de EGS/CVRS del cuestionario QLQ-C30 de la EORTC.
    9. Concentración sérica de atezolizumab en puntos temporales especificados.
    10. Incidencia de anticuerpos antifármaco (AAF) durante el estudio en relación con la prevalencia de AAF en el momento de inicio.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-8. Up to 7 years
    9-10. Day 1 of Cycle 1-4, 6, 10, and 15 and at treatment discontinuation visit (<= 30 days after last dose) and at 120 days after last dose of atezolizumab
    1-8. Hasta 7 años
    9-10. Día 1 del ciclo 1-4,6,10, u 15 y en la visita de discontinuación del tratamiento (<= 30 días después de la última dosis y a los 120 dias después de la última dosis de atezolizumab.
    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 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) 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) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Paclitaxel, Doxorubicin/Epirubicin, Cyclophosphamide
    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 concerned43
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA130
    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
    Australia
    Austria
    Belgium
    Brazil
    China
    Costa Rica
    Czech Republic
    Denmark
    France
    Germany
    Guatemala
    Hong Kong
    Hungary
    Ireland
    Israel
    Italy
    Japan
    Korea, Republic of
    Mexico
    Poland
    Romania
    Russian Federation
    Singapore
    Spain
    Switzerland
    Taiwan
    Thailand
    Ukraine
    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 is planned to end when approximately 289 deaths have been observed for the analysis of OS.
    El estudio está programado para finalizar cuando se han observado aproximadamente 289 muertes para el análisis de la SG.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years7
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years7
    E.8.9.2In all countries concerned by the trial months0
    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: 1150
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 1150
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state83
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 950
    F.4.2.2In the whole clinical trial 2300
    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)
    When appropriate, the Sponsor will offer access to atezolizumab to patients still benefiting from the treatment at the end of the study in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product. http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
    Cuando corresponda, el Patrocinador ofrecerá acceso a atezolizumab a los pacientes que aún se benefician del tratamiento al final del studio, de acuerdo con la Política Global de Roche sobre Acceso Continuo a Medicamentos de Investigación.
    http://www.roche.com/policy_continued_access_to_investigational_medicines.pdf
    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 Decision2018-04-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-03-01
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA