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The European Union Clinical Trials Register   allows you to search for protocol and results information on:
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    The EU Clinical Trials Register currently displays   43974   clinical trials with a EudraCT protocol, of which   7312   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 on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
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    Summary
    EudraCT Number:2018-001881-40
    Sponsor's Protocol Code Number:BO40747
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-06-17
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2018-001881-40
    A.3Full title of the trial
    A phase III, randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of Atezolizumab or placebo in combination with neoadjuvant doxorubicin + cyclophosphamide followed by paclitaxel + trastuzumab + pertuzumab in early HER2-positive breast cancer
    STUDIO CLINICO DI FASE III, RANDOMIZZATO, IN DOPPIO CIECO E CONTROLLATO CON PLACEBO VOLTO A VALUTARE L’EFFICACIA E LA SICUREZZA DI ATEZOLIZUMAB O PLACEBO IN ASSOCIAZIONE A DOXORUBICINA + CICLOFOSFAMIDE IN REGIME NEOADIUVANTE SEGUITI DA PACLITAXEL + TRASTUZUMAB + PERTUZUMAB NEL TRATTAMENTO DEL TUMORE MAMMARIO HER2 POSITIVO IN FASE INIZIALE
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Evaluate the Efficacy and Safety of Atezolizumab or Placebo in Combination with Neoadjuvant Doxorubicin + Cyclophosphamide Followed by Paclitaxel + Trastuzumab + Pertuzumab in Early HER2-Positive Breast Cancer
    STUDIO VOLTO A VALUTARE L’EFFICACIA E LA SICUREZZA DI ATEZOLIZUMAB O PLACEBO IN ASSOCIAZIONE A DOXORUBICINA + CICLOFOSFAMIDE IN REGIME NEOADIUVANTE SEGUITI DA PACLITAXEL + TRASTUZUMAB + PERTUZUMAB NEL TRATTAMENTO DEL TUMORE MAMMARIO HER2 POSITIVO IN FASE INIZIALE
    A.3.2Name or abbreviated title of the trial where available
    IMpassion050
    IMpassion050
    A.4.1Sponsor's protocol code numberBO40747
    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 Yes
    D.2.1.1.1Trade name Tecentriq
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH - AIC: EU/1/17/1220/001
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAtezolizumab
    D.3.2Product code [RO5541267/F03]
    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 INNAtezolizumab
    D.3.9.2Current sponsor codeRO5541267
    D.3.9.3Other descriptive nameTecentriq / MPDL3280A
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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 Perjeta
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH AIC: EU/1/13/813/001
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePertuzumab (rhuMAb 2C4)
    D.3.2Product code [RO4368451/F01]
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPertuzumab
    D.3.9.1CAS number 380610-27-5
    D.3.9.2Current sponsor codeRO4368451
    D.3.9.3Other descriptive namerhuMAb 2C4
    D.3.9.4EV Substance CodeSUB16455MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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: 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 Herceptin®
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH - AIC: EU/1/00/145/002
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTrastuzumab
    D.3.2Product code [RO0452317/V03]
    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 INNTrastuzumab
    D.3.9.1CAS number 180288-69-1
    D.3.9.2Current sponsor codeRO452317
    D.3.9.3Other descriptive nameHerceptin
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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 Yes
    D.3.11.13.1Other medicinal product typeHumanized monoclonal antibody
    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 Endoxan 1g
    D.2.1.1.2Name of the Marketing Authorisation holderBaxter Oncology GmbH - AIC 6035903.00.00
    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 [RO0042106]
    D.3.4Pharmaceutical form Powder 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.3.9.2Current sponsor codeRO0042106
    D.3.9.4EV Substance CodeSUB06859MIG
    D.3.10 Strength
    D.3.10.1Concentration unit g gram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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 DOXO-cell
    D.2.1.1.2Name of the Marketing Authorisation holderSTADApharm -AIC 44925.01.00
    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 nameDoxorubicin hydrochloride
    D.3.2Product code [RO0203296]
    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.3.9.2Current sponsor codeRO0203296
    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 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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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 typeFermentation product of the fungus Streptomyces peucetius
    D.IMP: 6
    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 - AIC 45636
    D.2.1.2Country which granted the Marketing AuthorisationSweden
    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 hydrochloride
    D.3.2Product code [RO0203296]
    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 INNDOXORUBICIN HYDROCHLORIDE
    D.3.9.2Current sponsor codeRO0203296
    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 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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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: 7
    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 - AIC 24615
    D.2.1.2Country which granted the Marketing AuthorisationIceland
    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 [RO0247506]
    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.3.9.2Current sponsor codeRO0247506
    D.3.9.4EV Substance CodeSUB09583MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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: 8
    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 holderTeva - AIC BE319672
    D.2.1.2Country which granted the Marketing AuthorisationBelgium
    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 [RO0247506]
    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.3.9.2Current sponsor codeRO0247506
    D.3.9.4EV Substance CodeSUB09583MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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: 9
    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 Kadcyla
    D.2.1.1.2Name of the Marketing Authorisation holderRoche Registration GmbH - AIC EU/1/13/885/002
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product name-
    D.3.2Product code [RO5304020]
    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 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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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: 10
    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 - AIC 8930/2016/05
    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 hydrochloride
    D.3.2Product code [RO0203296]
    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 INNDOXORUBICIN HYDROCHLORIDE
    D.3.9.2Current sponsor codeRO0203296
    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 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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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: 11
    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 - AIC 9154/2016/03
    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 [RO0247506]
    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.3.9.2Current sponsor codeRO0247506
    D.3.9.4EV Substance CodeSUB09583MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number6
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy 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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboSolution for infusion
    D.8.4Route of administration of the placeboIntravenous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Early Human epidermal growth factor receptor 2 (HER2)-positive breast cancer
    TUMORE MAMMARIO HER2 POSITIVO IN FASE INIZIALE
    E.1.1.1Medical condition in easily understood language
    HER2-positive breast cancer refers to breast cancer that tests positive for HER2 protein, which promotes the growth of cancer cells
    IL TUMORE MAMMARIO HER2 POSITIVO è UN TUMORE POSITIVO PER LE PROTEINE HER2, RESPONSABILI DELLA PROMOZIONE DELLA CRESCITA DELLE CELLULE CANCEROSE
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 23.0
    E.1.2Level PT
    E.1.2Classification code 10065430
    E.1.2Term HER2 positive breast cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    • To evaluate the efficacy of atezolizumab + dose-dense anthracycline
    (doxorubicin) + cyclophosphamide followed by paclitaxel + trastuzumab
    + pertuzumab [ddAC-PacHP] compared with placebo + ddAC-PacHP in
    HER2-positive early breast cancer (EBC) in the PD-L1-positive (IC 1/2/3) and the ITT populations on basis of pathological complete response (pCR) (ypT0/is ypN0)
    - Valutare l’efficacia di atezolizumab + ddAC PacHP rispetto a placebo + ddAC PacHP nel contesto del tumore mammario in fase iniziale (EBC)nella popolazione PD-L1-positiva (IC 1/2/3) e nella popolazione
    intent-to-treat (ITT), sulla base della risposta patologica completa
    E.2.2Secondary objectives of the trial
    • To evaluate the efficacy of atezolizumab + ddAC-PacHP compared with
    placebo + ddAC-PacHP in HER2-positive EBC on basis of pCR based upon hormone receptor status, pCR in the PD L1 negative (IC 0) population, and on the basis of event-free survival (EFS), disease-free survival
    (DFS), and overall survival (OS)
    • To evaluate patient-reported outcomes (PROs) of function and health-related quality of life (HRQoL) associated with atezolizumab + ddACPacHP compared with placebo + ddAC-PacHP, as measured by the
    European Organisation for Research and Treatment of Cancer (EORTC)
    Quality of Life Questionnaire-Core 30 (QLQ-C30)• To evaluate the safety of atezolizumab + ddAC-PacHP compared with placebo + ddAC-PacHP• To characterize the pharmacokinetic profile of atezolizumab, pertuzumab, trastuzumab, and trastuzumab emtansine
    • To evaluate the immune response to atezolizumab, trastuzumab, pertuzumab, and trastuzumab emtansine
    • To evaluate pCR, EFS, DFS, and OS based upon PIK3CA mutation status
    - Valutare l’efficacia di atezolizumab + ddAC PacHP rispetto a placebo + ddAC PacHP nel contesto dell’EBC sulla base di ­pCR (ypT0/is ypN0) in base allo stato dei recettori ormonali, ­pCR (ypT0/is ypN0), nella popolazione PD-L1-
    negativa (IC 0), sopravvivenza libera da eventi (EFS), ­sopravvivenza libera da malattia (DFS), ­sopravvivenza globale (OS).
    - Valutare gli outcome riferiti dai pazienti (PRO) relativi alla funzionalità e alla qualità di vita correlata alla salute (HRQoL) associati ad atezolizumab + ddAC PacHP rispetto ai soli ddAC PacHP secondo il Quality of Life Questionnaire-Core 30 (QLQ-C30) della European Organisation for Research and Treatment of Cancer (EORTC)
    - Valutare la sicurezza di atezolizumab + ddAC PacHP rispetto a placebo + ddAC-PacHP nel contesto dell’EBC
    - Caratterizzare il profilo farmacocinetico di atezolizumab, pertuzumab e trastuzumab somministrati in associazione
    - Valutare la risposta immunitaria ad atezolizumab, trastuzumab e pertuzumab
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    • Age >= 18 years
    • Ability to comply with the study protocol, in the investigator's judgment
    • Confirmed diagnosis of HER2-positive breast cancer, and hormone receptor and programmed death-ligand 1 (PD-L1) status, as documented through central testing of a representative tumor tissue specimen, is required
    • Primary breast tumor size of > 2 cm by radiographic measurement
    • Stage at presentation: T2-T4, N1-N3, M0 as determined by American Joint Committee on Cancer staging system, 8th edition
    • patients with hormone receptor-positive disease will be excluded once approximately 227 patients with hormone receptor-positive disease have been enrolled
    • Pathologic confirmation of nodal involvement with malignancy must be determined by fine-needle aspiration or core-needle biopsy. Surgical excision of lymph nodes is not permitted
    • • Patients with multifocal tumors are eligible provided at least one focus is sampled and centrally confirmed as HER2-positive
    • Patients with multicentric tumors are eligible provided all discrete lesions are sampled and centrally confirmed as HER2-positive
    • In patients with multifocal or multicentric breast cancer, the largest lesion should be measured to determine T stage
    • Patients with synchronous bilateral invasive disease are eligible so long as both lesions are HER2-positive
    • In case of bilateral cancer, the investigator has to decide prospectively which side will be evaluated for the primary endpoint
    • Patient agreement to undergo appropriate surgical management, including axillary lymph node surgery and partial or total mastectomy, after completion of neoadjuvant treatment
    • Eastern Cooperative Oncology Group Performance Status of 0 or 1
    • Baseline left ventricular ejection fraction >= 55% measured by echocardiogram or multiple-gated acquisition scans
    • Adequate hematologic and end-organ function
    • Negative HIV test at screening
    • Negative hepatitis B surface antigen (HBsAg) and negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening
    • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
    • • For women of childbearing potential: agreement to remain abstinent oruse contraceptive methods, and agreement to refrain from donating eggs, Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 5 months after the final dose of atezolizumab/placebo, 6 months after the final dose of doxorubicin, 12 months after the final dose of cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of trastuzumab, pertuzumab, or trastuzumab emtansine, whichever occurs last
    • For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm, men who are not surgically sterile must remain abstinent or use a condom plus an additional contraceptive method that together result in a failure rate of < 1% per year during the treatment period and for 6 months after the final dose of doxorubicin and/or cyclophosphamide, 6 months after the final dose of paclitaxel, and 7 months after the final dose of
    trastuzumab, pertuzumab or trastuzumab emtansine, whichever occurs last
    • For patients enrolled in the extended China enrollment phase: current resident of mainland China and of Chinese ancestry
    patients witch current grade >=2 peripheral neuropathy
    • Età >= 18 anni
    • Capacità di rispettare il protocollo dello studio secondo il giudizio dello sperimentatore
    • Stadio alla presentazione: T2-T4, N1-N3, M0 secondo il sistema di stadiazione AJCC, 8° edizione
    • I pazienti con malattia positiva per i recettori ormonali (positiva per i recettori degli estrogeni e/o del progesterone) verranno esclusi dopo che saranno stati arruolati circa 227 pazienti (il 50% della dimensione campionaria totale prefissata) con malattia positiva per i recettori ormonali.•La conferma patologica dell’interessamento linfonodale da parte della neoplasia maligna dovrà essere determinata mediante aspirazione con ago sottile o biopsia con ago a scatto. L’escissione chirurgica dei linfonodi non è ammessa.•I pazienti con tumori multifocali o multicentrici saranno ritenuti idonei a condizione che tutte le lesioni distinte vengano campionate e confermate come HER2-positive a livello centrale.•Per determinare lo stadio T nei pazienti con tumore mammario multifocale o multicentrico dovrà essere misurata la lesione maggiore.•I pazienti con malattia invasiva bilaterale sincrona saranno ritenuti idonei purché entrambe le lesioni siano HER2-positive.
    • In caso di tumore bilaterale, lo sperimentatore dovrà decidere prospetticamente quale lato valutare per l’endpoint primario.
    • Consenso del paziente a sottoporsi ad adeguate procedure chirurgiche, compresa l’asportazione dei linfonodi ascellari e la mastectomia parziale o totale, dopo aver completato il trattamento neoadiuvante.
    • Performance status secondo l’Eastern Cooperative Oncology Group pari a 0 o 1.
    • Frazione di eiezione del ventricolo sinistro (LVEF) basale >= 55% misurata mediante ecocardiogramma (ECO) o angiocardioscintigrafia (MUGA).
    • Adeguata funzionalità ematologica, epatica e renale,
    • Test di screening negativo per il virus dell’HIV
    - Test di screening negativo per l’antigene di superficie dell’epatite B (HBsAg), per gli anticorpi totali diretti contro l’antigene core dell’epatite B (HBcAb) o test di screening positivo per gli HBcAb totali seguito da un test di screening negativo per il DNA del virus dell’epatite B (HBV)
    - Test di screening negativo per gli anticorpi diretti contro il virus dell’epatite C (HCV) o test di screening positivo per gli anticorpi anti-HCV seguito da un test di screening negativo per l’HCV-RNA
    -Nelle donne in età fertile: consenso a praticare l’astinenza dai rapporti eterosessuali o a far uso di metodi contraccettivi, nonché consenso ad astenersi dalla donazione degli ovuli. Le donne dovranno praticare l’astinenza dai rapporti sessuali o far uso di metodi contraccettivi con tasso di insuccesso < 1% all’anno durante il periodo di trattamento e per 5 mesi dopo l’ultima dose di atezolizumab/placebo, 6 mesi dopo l’ultima dose di doxorubicina, 12 mesi dopo l’ultima dose di ciclofosfamide, 6 mesi dopo l’ultima dose di paclitaxel e 7 mesi dopo l’ultima dose di trastuzumab e/o pertuzumab, a seconda della dose somministrata per ultima. -Per gli uomini: consenso a praticare l’astinenza dai rapporti eterosessuali o a far uso di metodi contraccettivi, nonché consenso ad astenersi dalla donazione del seme, Gli uomini non vasectomizzati con partner di sesso femminile in età fertile non in gravidanza dovranno praticare l’astinenza dai rapporti sessuali o usare il preservativo insieme a un altro metodo contraccettivo che, in associazione al profilattico, garantisca un tasso di insuccesso < 1% all’anno durante il periodo di trattamento e per 6 mesi dopo l’ultima dose di doxorubicina e/o ciclofosfamide, 6 mesi dopo l’ultima dose di paclitaxel e 7 mesi dopo l’ultima dose di trastuzumab e/o pertuzumab, a seconda della dose somministrata per ultima.
    Per i pz arruolati nella fase estesa di arruolamento cinese: attuale residenza nella
    Cina continentale e origine cinese. La sottopopolazione cinese sarà costituita da pz di origine cinese arruolati presso centri situati nella Cina continentale e a Taiwan.•Neuropatia periferica di grado >=2 in atto.
    E.4Principal exclusion criteria
    • Prior history of invasive breast cancer
    • Stage IV (metastatic) breast cancer
    • Prior systemic therapy for treatment of breast cancer
    • Previous therapy with anthracyclines or taxanes for any malignancy
    • Ulcerating breast cancer
    • Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
    • Sentinel lymph node procedure or axillary lymph node dissection prior to initiation of neoadjuvant therapy
    • History of other malignancy within 5 years prior to screening, with the exception of those who patients have a negligible risk of metastasis or death, such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer
    • Cardiopulmonary dysfunction
    • Dyspnea at rest
    • Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis
    • History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography scan
    • Active tuberculosis
    • 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 study
    • Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
    • Treatment with therapeutic antibiotics within 2 weeks (IV antibiotics) or 5 days (oral antibiotics) prior to initiation of study treatment
    • Prior allogeneic stem cell or solid organ transplantation
    • Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug and may affect the interpretation of the results, or may render the patient at high risk from treatment complications
    • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab/placebo treatment or within 5 months after the final dose of atezolizumab/placebo
    • Treatment with investigational therapy within 28 days prior to initiation of study treatment
    • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-cytotoxic T lymphocyte-associated protein-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
    • Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
    • Treatment with systemic immunosuppressive medication within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment
    • History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
    • Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
    • Known allergy or hypersensitivity to the components of the paclitaxel, cyclophosphamide, or doxorubicin formulations
    • Known allergy or hypersensitivity to trastuzumab or pertuzumab formulations
    • Pregnancy or breastfeeding (for details see the protocol)
    - Anamnesi positiva per tumore mammario invasivo
    - Tumore mammario in stadio IV (metastatico)
    - Precedente terapia sistemica per il trattamento del tumore mammario
    - Precedente terapia con antracicline o taxani per qualsiasi neoplasia maligna
    • Tumore mammario ulcerato
    • Biopsia incisionale e/o escissionale del tumore prim e/o dei linfonodi ascellari
    • Procedura del linfonodo sentinella o dissezione dei linfonodi ascellari prima dell’inizio della terapia neoadiuvante
    • Anamnesi positiva per altra neoplasia maligna nei 5 anni precedenti lo screening, ad eccezione di quelle in cui i pazienti sono esposti a un rischio trascurabile di metastasi o decesso, quali forme adeguatamente trattate di carcinoma in situ della cervice, carcinoma cutaneo non melanomatoso, tumore localizzato della prostata, carcinoma duttale in situ o tumore uterino in stadio I
    • Disfunzione cardiopolmonare
    • Dispnea a riposo
    • Presenza attiva di anamnesi positiva per malattia autoimmune o immunodeficienza, ivi inclusi, a mero titolo esemplificativo, miastenia grave, miosite, epatite autoimmune, lupus eritematoso sistemico, artrite reumatoide, malattia infiammatoria intestinale, sindrome da anticorpi antifosfolipidi, granulomatosi di Wegener, sindrome di Sjögren, sindrome di Guillain-Barré o sclerosi multipla
    - Anamnesi positiva per fibrosi polmonare idiopatica, polmonite in organizzazione (per es. bronchiolite obliterante), polmonite indotta da farmaci o polmonite idiopatica, oppure evidenza di polmonite attiva alla tomografia computerizzata (TC) del torace allo screening
    - Tubercolosi attiva
    • Procedura chirurgica maggiore, per ragioni diverse dalla diagnosi, nelle 4 settimane precedenti l’inizio del trattamento in studio o necessità prevista di una procedura chirurgica maggiore durante lo studio
    • Infezione severa nelle 4 settimane precedenti l’inizio del trattamento in studio, ivi inclusi, a mero titolo esemplificativo, ricoveri ospedalieri per complicanze dell’infezione, batteriemia o polmonite severa
    • Trattamento con antibiotici terapeutici nelle 2 settimane (antibiotici per via e.v.) o nei 5 g (antibiotici orali) precedenti l’inizio del trattamento
    • Precedente trapianto allogenico di cellule staminali o di organi solidi
    • Qualsiasi altra malattia, disfunzione metabolica, obiettività o referto di laboratorio che rappresenti una controindicazione all’uso di un farmaco sperimentale e che possa interferire con l’interpretazione dei risultati o che esponga il paziente ad alto rischio di complicanze correlate al trattamento
    • Trattamento con un vaccino vivo attenuato nelle 4 settimane precedenti l’inizio del trattamento o necessità prevista di somministrare un tale vaccino durante il trattamento con atezo/placebo o nei 5 mesi successivi l’ultima dose di atezo/placebo
    • Trattamento con terapia sperimentale nei 28 g precedenti l’inizio del trattamento
    • Precedente trattamento con agonisti di CD137 o terapie che bloccano i checkpoint immunitari
    • Trattamento con immunostimolanti sistemici nelle 4 settimane o nelle 5 emivite del farmaco (qualora queste ultime abbiano durata superiore) precedenti l’inizio del trattamento
    • Trattamento con immunosoppressori sistemici nelle 2 settimane precedenti l’inizio del trattamento in studio o necessità prevista di immunosoppressori sistemici durante il trattamento
    • Anamnesi positiva per reazioni allergiche anafilattiche severe agli anticorpi chimerici o umanizzati, o alle proteine di fusione
    • Ipersensibilità nota ai prodotti contenenti cellule ovariche di criceto cinese o a qualsiasi componente della formulazione di atezo; delle formulazioni di paclitaxel, ciclofosfamide o doxorubicina, e delle formulazioni di trastuzumab o pertuzumab
    • Gravidanza o allattamento secondo quanto riportato nel protocollo
    E.5 End points
    E.5.1Primary end point(s)
    1. pCR in the PD-L1-positive and ITT populations
    1. pCR nella popolazione PD-L1-positiva e ITT
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Up to 54 months
    1. fino a 54 mesi
    E.5.2Secondary end point(s)
    1. pCR (ypT0/is ypN0) based upon hormone receptor status
    2. pCR (ypT0/is ypN0) in the PD L1 negative (IC 0) population
    3. EFS in all patients and based upon hormone receptor status (ER/PgR positive or ER/PgR negative) and PD-L1 status (IC 0; IC 1/2/3)
    4. DFS in all patients who undergo surgery and based upon hormone receptor status (ER/PgR positive or ER/PgR negative) and PD-L1 status (IC 0; IC 1/2/3)
    5. OS in all patients and based upon hormone receptor status (ER/PgR positive or ER/PgR negative) and PD-L1 status (IC 0; IC 1/2/3)
    6. 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
    7. Incidence and severity of adverse events, with severity determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0
    8. Change from baseline in targeted vital signs
    9. Change from baseline in targeted clinical laboratory test results
    10. Maximum serum concentration observed [Cmax] and minimum serum concentration under steady-state conditions within a dosing interval [Cmin]) of atezolizumab concentrations in serum at specified timepoints
    11. Cmin for pertuzumab, trastuzumab, and trastuzumab emtansinse in serum at specified timepoints
    12. Incidence of treatment-emergent anti-drug antibodies (ADAs) to atezolizumab, trastuzumab, pertuzumab, and trastuzumab emtansine
    13. pCR (ypT0/is ypN0) based upon PIK3CA mutation status
    14. EFS based upon PIK3CA mutation status
    15. DFS based upon PIK3CA mutation status
    16. OS based upon PIK3CA mutation status
    1. pCR (ypT0/is ypN0) in base allo stato dei recettori ormonali
    2. pCR (ypT0/is ypN0) in base allo stato di PD-L1 (IC 0; IC 1/2/3).3. EFS
    3. Sopravvivenza libera da eventi (EFS) in tutti pz e basato sullo stato ormone recettore (ER/PgR positive o ER/PgR negative) e lo stato PD-L1 (IC 0; IC 1/2/3)
    4. Sopravvivenza libera da malattia (DFS),n tutti i pazienti sottoposti a chirurgia e basati sullo stato del recettore ormonale (ER / PgR positivo o ER / PgR negativo) e sullo stato di PD-L1 (IC 0; IC 1/2/3)
    5. Sopravvivenza globale (OS) in tutti i pazienti e basato sullo stato del recettore ormonale (ER / PgR positivo o ER / PgR negativo) e sullo stato di PD-L1 (IC 0; IC 1/2/3)
    6. Media e variazione media rispetto al punteggio basale della funzionalità (nel ruolo, fisica) e delle condizioni generali di salute (GHS)/HRQoL in funzione del timepoint di valutazione e tra i bracci di trattamento secondo le scale funzionali e GHS/HRQoL del questionario EORTC QLQ-C30.
    7. Incidenza e severità degli eventi avversi, con severità stabilita in base ai criteri comuni di terminologia per gli eventi avversi del National Cancer Institute, versione 5.0 (NCI CTCAE v5.0).
    8. Variazione dei parametri vitali di interesse rispetto al basale
    9. Variazione dei risultati degli esami clinici di laboratorio di interesse rispetto al basale
    10. Concentrazioni di picco e di valle (massima concentrazione sierica osservata [Cmax] e minima concentrazione sierica in condizioni di stato stazionario entro un intervallo posologico [Cmin]) di atezolizumab nel siero a specifici timepoint
    11. Cmin per pertuzumab, trastuzumab e trastuzumab emtansinse nel siero a orari prestabiliti
    12. Incidenza di anticorpi anti-farmaco (ADA) emergenti dal trattamento con atezolizumab, trastuzumab, pertuzumab e trastuzumab emtansine
    13. pCR (ypT0 / is ypN0) basato sullo stato di mutazione PIK3CA
    14. EFS basato sullo stato di mutazione PIK3CA
    15. DFS basato sullo stato di mutazione PIK3CA
    16. Sistema operativo basato sullo stato di mutazione PIK3CA
    E.5.2.1Timepoint(s) of evaluation of this end point
    1-5. Up to 54 months
    6. Day 1 of Cycle 1-9, on Day 1 of every other cycle thereafter until Cycle 22; at the treatment discontinuation or early termination visit and follow up visit
    7. Up to 54 months
    8-9. Baseline (Day 1) to 54 months
    10. Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit 11. For pertuzumab, trastuzumab: Day 1 of Cycle 1, 8, 12, at treatment discontinuation visit; For trastuzumab emtansine: Day 1 of Cycle 9 and
    12; at treatment discontinuation visit
    12. For atezolizumab: Day 1 of Cycle 1, 2, 3, 4, 8, 12, 16, at treatment discontinuation visit; For pertuzumab, trastuzumab: Day 1 of Cycle 1, 8, 12, at treatment discontinuation visit; For trastuzumab emtansine: Day 1 of Cycle 9 and 12; at treatment discontinuation visit 13-16. Up to 54 months
    1-5. fino a 54 mesi 6. Giorno 1 dei Cicli 1-9, Giorno 1 di ogni altro Ciclo fino al Ciclo 22; ad interruzione del tratt o ad una visita di fine trattamento anticipato e alla visita di fu 7. Fino a 54 mesi 8-9. Baseline (giorno 1) a 54 mesi10. Giorno 1 del ciclo 1, 2, 3, 4, 8, 12, 16, alla visita di interruzione del tratt 11.Per peruz, trastuz: giorno 1 del ciclo 1, 8, 12, alla visita di sospensione del tratt; Per trastuz emtansine:1 ° giorno del ciclo 9 e12; alla visita di cessazione del tratt12. Per atezo: giorno 1 del ciclo 1, 2, 3, 4, 8, 12, 16, alla visita di interruzione del tratt; Per pertuz,trastuz: giorno 1 del ciclo 1, 8, 12, alla visita di interruzione del tratt; Per trastuz emtansine: giorno 1 del ciclo 9 e 12;alla visita di interruzione del trattamento13-16. Fino a 54 mesi
    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
    To evaluate the immune response
    Valutazione risposta immune
    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 No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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 Yes
    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 EEA40
    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 Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Brazil
    Canada
    China
    Japan
    Korea, Republic of
    Russian Federation
    Taiwan
    United States
    Germany
    Italy
    Poland
    Spain
    Czechia
    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
    LVLS, The end of the study is expected to occur approximately 36 months after the last patient is enrolled.
    LVLS, la fine dello studio coinciderà con la data in cui si terrà l’ultima visita dell’ultimo paziente. Lo studio dovrebbe terminare circa 36 mesi dopo l’arruolamento dell’ultimo paziente.
    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 months2
    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 months2
    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: 408
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 45
    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 state19
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 170
    F.4.2.2In the whole clinical trial 283
    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)
    Roche non prevede di fornire il farmaco dello studio o qualsiasi altro trattamento o di farsi carico di interventi dopo che Lei avrà terminato lo studio o se Lei interrompe il trattamento o viene interrotta la Sua partecipazione allo studio.Roche valuterà se continuare a fornire atezo,pertuzumab e trastuzumab in accordo alla Policy Globale di Roche sull'accesso ai medicinali sperimentali,disponibile al seguente sito:
    http://www.roche.com/policy_continued_access_to_investigational_medicines
    The Sponsor does not have any plans to provide Roche IMPs (atezolizumab, pertuzumab, and trastuzumab) or any other study treatments or interventions to patients who have completed the study. The Sponsor may evaluate whether to continue providing atezolizumab, pertuzumab, and trastuzumab in accordance with the Roche Global Policy on Continued Access to Investigational Medicinal Product, available at:
    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 Decision2018-11-09
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-10-17
    P. End of Trial
    P.End of Trial StatusOngoing
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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