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    The EU Clinical Trials Register currently displays   35495   clinical trials with a EudraCT protocol, of which   5837   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2017-002361-22
    Sponsor's Protocol Code Number:D5336C00001
    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:2017-12-13
    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 number2017-002361-22
    A.3Full title of the trial
    A Phase II, Open Label, Randomised, Multi-centre Study to Assess the Safety and Efficacy of Agents Targeting DNA Damage Repair in Combination with Olaparib versus Olaparib Monotherapy in the Treatment of Metastatic Triple Negative Breast Cancer Patients Stratified by Alterations in Homologous Recombinant Repair (HRR)-related Genes (including BRCA1/2) (VIOLETTE)
    Estudio de fase II, abierto, aleatorizado y multicéntrico, para evaluar la seguridad y la eficacia de agentes dirigidos frente a los mecanismos de reparación del ADN en combinación con olaparib, en comparación con olaparib en monoterapia, en el tratamiento de pacientes con cáncer de mama metastásico triple negativo con estratificación en función de sus alteraciones en los genes recombinantes de reparación homóloga (incluido BRCA1/2) (VIOLETTE)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase II, Open Label, Randomised, Multi-centre Study to Assess the Safety and Efficacy of Agents Targeting DNA Damage Repair in Combination with Olaparib versus Olaparib Monotherapy in the Treatment of Metastatic Triple Negative Breast Cancer Patients (VIOLETTE Study)
    Estudio de fase II, abierto, aleatorizado y multicéntrico, para evaluar la seguridad y la eficacia de agentes dirigidos frente a los mecanismos de reparación del ADN en combinación con olaparib, en comparación con olaparib en monoterapia, en el tratamiento de pacientes con cáncer de mama metastásico triple negativo (Estudio VIOLETTE)
    A.4.1Sponsor's protocol code numberD5336C00001
    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 SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    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 supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca AB
    B.5.2Functional name of contact pointInformation Center
    B.5.3 Address:
    B.5.3.1Street Addressnot applicable
    B.5.3.2Town/ citynot applicable
    B.5.3.3Post codenot applicable
    B.5.3.4CountryUnited States
    B.5.6E-mailinformation.center@astrazeneca.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 nameOlaparib
    D.3.2Product code AZD2281
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOlaparib
    D.3.9.1CAS number 763113-22-0
    D.3.9.2Current sponsor codeAZD2281
    D.3.9.4EV Substance CodeSUB32234
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 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 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 nameOlaparib
    D.3.2Product code AZD2281
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNOlaparib
    D.3.9.1CAS number 763113-22-0
    D.3.9.2Current sponsor codeAZD2281
    D.3.9.4EV Substance CodeSUB32234
    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 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 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 nameAZD6738
    D.3.2Product code AZD6738
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available
    D.3.9.1CAS number 1352226-88-0
    D.3.9.2Current sponsor codeAZD6738
    D.3.9.3Other descriptive nameAZ13386215
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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: 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 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 nameAZD6738
    D.3.2Product code AZD6738
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available
    D.3.9.1CAS number 1352226-88-0
    D.3.9.2Current sponsor codeAZD6738
    D.3.9.3Other descriptive nameAZ13386215
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number80
    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 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 nameAZD6738
    D.3.2Product code AZD6738
    D.3.4Pharmaceutical form Film-coated tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available
    D.3.9.1CAS number 1352226-88-0
    D.3.9.2Current sponsor codeAZD6738
    D.3.9.3Other descriptive nameAZ13386215
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 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 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 nameAZD1775
    D.3.2Product code AZD1775
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available
    D.3.9.1CAS number 1277170-60-1
    D.3.9.2Current sponsor codeAZD1775
    D.3.9.3Other descriptive nameMK-1775 hemihydrate; L001739996-008U
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number25
    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: 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 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 nameAZD1775
    D.3.2Product code AZD1775
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available
    D.3.9.1CAS number 1277170-60-1
    D.3.9.2Current sponsor codeAZD1775
    D.3.9.3Other descriptive nameMK-1775 hemihydrate; L001739996-008U
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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: 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 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 nameAZD1775
    D.3.2Product code AZD1775
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available
    D.3.9.1CAS number 1277170-60-1
    D.3.9.2Current sponsor codeAZD1775
    D.3.9.3Other descriptive nameMK-1775 hemihydrate; L001739996-008U
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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: 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 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 nameAZD1775
    D.3.2Product code AZD1775
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available
    D.3.9.1CAS number 1277170-60-1
    D.3.9.2Current sponsor codeAZD1775
    D.3.9.3Other descriptive nameMK-1775 hemihydrate; L001739996-008U
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 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 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 nameAZD1775
    D.3.2Product code AZD1775
    D.3.4Pharmaceutical form Capsule
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNnot available
    D.3.9.1CAS number 1277170-60-1
    D.3.9.2Current sponsor codeAZD1775
    D.3.9.3Other descriptive nameMK-1775 hemihydrate; L001739996-008U
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number200
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.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
    Cáncer de mama triple negativo
    E.1.1.1Medical condition in easily understood language
    Breast Cancer
    Cáncer de mama
    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 10075566
    E.1.2Term Triple negative 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
    For BRCAm, Non BRCAm HRRm, Non HRRm subject population

    - To assess the efficacy of the combination of AZD6738+olaparib and the combination of AZD1775+olaparib compared with olaparib monotherapy by assessment of PFS
    Para población de pacientes BRCAm, Non BRCAm HRRm, Non HRRm

    - Evaluar la eficacia de la combinación de AZD6738+olaparib y de la combinación de AZD1775+olaparib en comparación con olaparib en monoterapia en cuanto a la supervivencia sin progresión (progression free survival, PFS)
    E.2.2Secondary objectives of the trial
    -To assess the efficacy of combination of AZD6738+olaparib and combination of AZD1775+olaparib compared with olaparib monotherapy by assessment of PFS for HRRm and All subject populations
    -To assess the efficacy of combination of AZD6738+olaparib and combination of AZD1775+olaparib compared with olaparib monotherapy in terms of ORR, DOR, tumour change and OS
    - To compare the efficacy of combination of AZD6738+olaparib with combination of AZD1775+olaparib in terms of PFS, ORR, DOR, tumour change and OS
    -To explore the frequency of and describe the nature of tumour HRR (including BRCA) mutation(s) in tumour samples and to compare this with germline HRR (including BRCA) mutation status
    -To assess exposure to olaparib, AZD6738 and AZD1775 in all patients
    -To assess the safety and tolerability of combination of AZD6738+olaparib and combination of AZD1775+olaparib compared with olaparib monotherapy
    -Evaluar la eficacia de la combinación de AZD6738+olaparib y de AZD1775+olaparib en comparación con olaparib en monoterapia en cuanto a la PFS para la población de pacientes HRRm y Total
    -Evaluar la eficacia de la combinación de AZD6738+olaparib y de AZD1775+olaparib en comparación con olaparib en monoterapia en cuanto a la tasa de respuesta objetiva(ORR), duración de respuesta(DoR), cambios en el tumor y supervivencia global(OS)
    -Comparar la eficacia de la combinación de AZD6738+olaparib y de AZD1775+olaparib en cuanto a PFS, ORR, DOR, cambios en el tumor y OS
    -Explorar la frecuencia y describir la naturaleza de la(s) mutación(es) en la HRR (incluido BRCA) en muestras de tumor y compararlas con el estado de mutación en HRR de la línea germinal (incluida BRCA)
    -Evaluar la exposición al olaparib, a AZD6738 y a AZD1775 en todos los pacientes
    -Evaluar la seguridad y la tolerabilidad de la combinación de AZD6738+olaparib y de AZD1775+olaparib en comparación con olaparib en monoterapia
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Provision of informed consent prior to any study specific procedures
    2. Patients must be male or female ≥18 years of age
    3. Progressive cancer at the time of study entry
    4. Histologically or cytologically confirmed TNBC with evidence of metastatic disease (defined as ER and PgR negative [IHC nuclear staining <1% positive] and HER2 negative [IHC 0, 1+ or IHC 2+ with corresponding ISH non-amplified of ratio less than 2.0 or ISH non-amplified ratio less than 2.0]
    5. Patients must have received at least 1 and no more than 2 prior lines of treatment for metastatic disease with an anthracycline (doxorubicin, epirubicin) and/or a taxane (eg, paclitaxel, docetaxel) unless contraindicated, in either the neo-adjuvant, adjuvant or metastatic setting
    Patients who have received platinum (cisplatin or carboplatin, either as monotherapy or in combination) for advanced breast cancer are eligible to enter the study provided there has been no evidence of disease progression during the platinum chemotherapy
    Patients who have received prior platinum based chemotherapy are eligible if platinum was given either as potentially curative treatment for a prior non breast cancer (ovarian cancer) with no evidence of disease for ≥5 years prior to study entry or as adjuvant/neoadjuvant treatment for breast cancer provided at least 12 months have elapsed between the last dose of platinum-based treatment and randomisation
    6. Confirmed presence of qualifying HRR mutation or absence of any HRR mutation in tumour tissue by the Lynparza HRR assay
    - FFPE tumour tissue blocks are required for each patient, but if not available, tissue sections are accepted. At least twenty (thirty preferable) unstained sections without cover slips must be submitted to ensure sufficient material for the prospective Lynparza HRR testing to determine study eligibility and research that will aid understanding of the patient population relative to treatment with DDR and other cancer agents
    - If a patient has a previously known qualifying BRCA1/2 mutation (in blood or tumour tissue), then the patient can be invited to consent to the full study. The patient will need to consent to provide an archival tumour block or tissue sections for central assessment of the HRR mutation status
    - If patients have a mutation in one of the other non BRCA HRR genes based on prior breast cancer tissue specimen testing by the commercially available FoundationOne® assay, they must have the mutation confirmed as a qualifying mutation by FMI. If patients have no detected mutation in any of the HRR genes based on prior breast cancer tissue specimen testing by the FoundationOne® assay, they must have the lack of HRR mutation confirmed by FMI. The patient will need to consent to provide an archival tumour sample (tissue block or sections) and a blood sample
    7. At least one measurable lesion that can be accurately assessed at baseline by computed tomography (CT) (magnetic resonance imaging [MRI] where CT is contraindicated) and is suitable for repeated assessment as per RECIST 1.1
    8. Patients must have normal organ and bone marrow function measured within 28 days prior to randomisation as defined below:
    a) Haemoglobin ≥10.0 g/dL with no blood transfusions (packed red blood cells) in the past 28 days
    b) Absolute neutrophil count ≥ 1.5 x 109 /L
    c) Platelet count ≥100 x 109 /L with no platelet transfusions in the past 28 days
    d) Total bilirubin ≤1.5 x institutional upper limit of normal unless the patient has documented Gilbert’s Syndrome
    e) Aspartate aminotransferase /alanine aminotransferase ≤2.5 x institutional ULN unless liver metastases are present in which case they must be ≤5 x ULN
    f) Patients must have creatinine clearance estimated using the Cockcroft-Gault equation of ≥51 mL/min:
    Estimated CrCl = (140-age [years]) x weight (kg) (x F) / serum creatinine (mg/dL) x 72
    where F=0.85 for females and F=1 for males
    9. ECOG PS 0-1 within 28 days of randomisation
    10. Postmenopausal or evidence of non childbearing status for women of childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and confirmed prior to treatment on Day 1
    Postmenopausal is defined as:
    - Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments
    - Luteinizing hormone and Follicle stimulating hormone levels in the postmenopausal range for women under 50
    - radiation-induced oophorectomy with last menses >1 year ago
    - chemotherapy-induced menopause with >1 year interval since last menses
    - surgical sterilisation (bilateral oophorectomy or hysterectomy)
    11. Women of childbearing potential and their partners, who are sexually active, must agree to the use of 2 highly effective forms of contraception in combination from the signing of the informed consent, throughout the period of taking study treatment and for at least 1 month after last dose of study drug(s)
    Please see protocol for further details
    1. Obtención del consentimiento informado antes de cualquier procedimiento específico del estudio
    2. Paciente hombre o mujer de edad ≥18 años
    3. Cáncer en progresión en el momento de entrada en el estudio
    4. Cáncer de mama triple negativo (TNBC), confirmado histológica o citológicamente, con evidencia de enfermedad metastásica (se define como negatividad de ER y PgR [tinción nuclear por IHC con positividad <1%] y negatividad del HER2 [IHC 0, 1+ o IHC 2+junto con un cociente <a 2.0 por ISH no amplificada o un cociente <a 2.0 por ISH no amplificada]
    5. Deberán haber recibido un mínimo de 1 y un máximo de 2 líneas previas de tratamiento por enfermedad metastásica con una antraciclina (doxorrubicina, epirrubicina) y/o un taxano (eg, paclitaxel, docetaxel), salvo en caso de contraindicación, en el ámbito neoadyuvante, adyuvante o metastásico
    Pacientes que hayan recibido platino (cisplatino o carboplatino, ya sea en monoterapia o en combinación) por cáncer de mama avanzado, a condición de que no se haya producido progresión de su enfermedad durante la quimioterapia con platino.
    Pacientes que hayan recibido anteriormente quimioterapia con platino como tratamiento potencialmente curativo por un cáncer previo distinto del cáncer de mama (cáncer de ovario) si se han mantenido sin evidencia de enfermedad durante ≥5 años anteriores a la entrada en el estudio, o como tratamiento adyuvante/neoadyuvante por cáncer de mama, a condición de que hayan transcurrido como mínimo 12 meses entre la última dosis del tratamiento basado en el platino y la aleatorización
    6. Confirmación de la presencia de la mutación de HRR cualificadora para el estudio o ausencia de una mutación de HRR en el tejido tumoral mediante el Lynparza HRR assay
    - Deberá disponerse de una muestra de tejido tumoral fijado en FFPE, pero, si no se dispone de ella, se aceptan cortes de tejido. Deberán presentarse como mínimo 20 (preferiblemente, 30) cortes sin teñir, sin cubreobjetos, para asegurar un material suficiente para la prueba prospectiva mediante el Lynparza HRR assay para determinar la elegibilidad para el estudio y para la investigación que pueda ayudar a definir la población de pacientes en cuanto al tratamiento con DDR y otros agentes antineoplásicos
    - Si se conociera que previamente ha presentado una mutación de BRCA1/2 cualificadora (en sangre o en tejido tumoral), podrá invitársele a que otorgue su consentimiento para el estudio completo. Deberá otorgar también su consentimiento para proporcionar un bloque de tumor de archivo o cortes de tejido para estudio central del estado de mutación de HRR
    - Si presenta una mutación en uno de los otros genes de HRR distintos de BRCA en el estudio de una muestra previa de tejido de cáncer de mama mediante el FoundationOne® assay comercializado, deberá confirmarse la mutación como mutación cualificadora para el estudio mediante FMI. Si no se detecta mutación en ninguno de los genes de la HRR en el estudio de la muestra previa de tejido de cáncer de mama mediante el FoundationOne® assay, deberá confirmarse por FMI la ausencia de mutación de HRR. El paciente deberá otorgar su consentimiento para la obtención de una muestra de tumor de archivo (bloque o cortes de tejido) y una muestra de sangre
    7. Como mínimo una lesión medible que pueda evaluarse con precisión en el momento basal por tomografía computerizada (CT) (resonancia magnética [MRI] si CT estuviera contraindicada) y adecuada para su evaluación repetida mediante RECIST 1.1
    8. Funciones orgánicas y de médula ósea normales en su medición en el plazo de los 28 días anteriores a la aleatorización. Se define como normalidad lo siguiente:
    a) Hemoglobina ≥10,0g/dL sin transfusiones (concentrados de hematíes) en los 28 últimos días
    b) Recuento absoluto de neutrófilos ≥1,5x109/L
    c) Recuento de plaquetas ≥100x109/L sin transfusiones de plaquetas en los 28 últimos días
    d) Bilirrubina total ≤1,5 x límite superior de la normalidad del centro (ULN), salvo en caso de síndrome de Gilbert documentado
    e) Aspartato aminotransferasa /alanina aminotransferasa ≤2,5xULN del centro, salvo en presencia de metástasis hepáticas, en cuyo caso deberán ser ≤5xULN
    f) Aclaramiento de creatinina estimado mediante la ecuación de Cockcroft-Gault ≥51 mL/min:
    CrCl estimado =(140-edad[años]) x peso(kg) (x F)/creatinina sérica (mg/dL) x72
    F=0,85 en la mujer y F=1 en el varón
    9. ECOG 0-1 en los 28 días anteriores a la aleatorización
    10. En mujeres potencialmente fértiles, en posmenopausia o evidencia de ausencia de embarazo: prueba de embarazo en orina o suero negativa en los 28 días anteriores al inicio del tratamiento y confirmada antes del tratamiento el Día 1
    (...)
    Para una mayor información, véase el protocolo
    E.4Principal exclusion criteria
    1. Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and/or staff at the study site)
    2. Cytotoxic chemotherapy, hormonal or non hormonal targeted therapy within 21 days of Cycle 1 Day 1 is not permitted. Palliative radiotherapy must have been completed 21 or more days before Cycle 1 Day 1. The patient can receive a stable dose of bisphosphonates or denosumab for bone metastases, before and during the study as long as these were started at least 5 days prior to study treatment
    3. More than 2 prior lines of cytotoxic chemotherapy for metastatic disease
    - Prior treatments with hormonal therapy and non hormonal targeted therapy are allowed and not counted as a prior line of cytotoxic chemotherapy
    - For the purposes of this protocol, the combination of an aromatase inhibitor and everolimus is not considered cytotoxic chemotherapy
    - Treatment with biologics will not be considered as prior line of therapy
    4. Previous randomisation in the present study
    5. Previous treatment with a PARP inhibitor (including olaparib) or other DDR inhibitor (unless treatment was for less than 3 weeks duration and at least 12 months have elapsed between the last dose and randomisation. Patients that did not tolerate prior treatment are excluded)
    6. Exposure to a small molecule IP within 30 days or 5 half-lives (whichever is longer) prior to randomisation. The minimum washout period for immunotherapy shall be 42 days
    7. Patients with MDS/AML or with features suggestive of MDS/AML
    8. Patients with second primary cancer, EXCEPTIONS: adequately treated non melanoma skin cancer, curatively treated in-situ cancer of the cervix, Ductal Carcinoma in Situ (DCIS), stage 1 grade 1 endometrial carcinoma, or other solid tumours curatively treated with no evidence of disease for ≥ 5 years prior to study entry (including lymphomas [without bone marrow involvement])
    9. Mean resting corrected QTc interval using the Fridericia formula (QTcF) >470 msec/female patients and >450 msec for male patients (as calculated per institutional standards) obtained from 3 ECGs performed 2-5 minutes apart at study entry, or congenital long QT syndrome AZD1775 should not be given to patients who have a history of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected. AZD1775 has not been studied in patients with ventricular arrhythmias or recent myocardial infarction
    10. Any of the following cardiac diseases currently or within the last 6 months defined by New York Heart Association (NYHA) ≥ Class 2:
    - Unstable angina pectoris
    - Congestive heart failure
    - Acute myocardial infarction
    - Conduction abnormality not controlled with pacemaker or medication
    - Significant ventricular or supraventricular arrhythmias (patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible)
    11. Concomitant use of known strong cytochrome P (CYP) 3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks
    Patient has had prescription or non-prescription drugs or other products known to be sensitive CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks prior to Day 1 of dosing and withheld throughout the study until 2 weeks after the last dose of study drug
    Transporter studies (in vitro) have shown that AZD1775 is an inhibitor of breast cancer resistance protein (BCRP) Patients should stop using herbal medications 7 days prior to first dose of study treatment
    12. Concomitant use of known strong (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John’s Wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
    13. Persistent toxicities (≥ CTCAE grade 2) caused by previous cancer therapy, excluding alopecia and CTCAE grade 2 peripheral neuropathy
    14. Major surgery within 2 weeks of starting study treatment: patients must have recovered from any effects of any major surgery
    15. Immunocompromised patients, eg, patients who are known to be serologically positive for human immunodeficiency virus (HIV)
    16. Patients with known active hepatitis (ie, hepatitis B or C)
    Please see protocol for further details
    1. Participación en la planificación y/o desarrollo del estudio (aplicable al personal de AstraZeneca y/o del centro del estudio)
    2. No se permiten la quimioterapia citotóxica, el tratamiento hormonal o el tratamiento dirigido no hormonal en el plazo de los 21 días anteriores al Día 1 Ciclo 1. En caso de radioterapia paliativa, deberá haber finalizado 21 o más días antes del Día 1 Ciclo 1. El paciente podrá recibir una dosis estable de bisfosfonatos o denosumab por metástasis hepáticas antes y durante el estudio, a condición de que dicho fármaco se haya iniciado como mínimo 5 días antes del tratamiento del estudio
    3. Más de dos líneas previas de quimioterapia citotóxica por enfermedad metastásica
    - Se permiten el tratamiento hormonal previo y el tratamiento dirigido no hormonal previo, que no se contarán como una línea previa de quimioterapia citotóxica
    - A los fines de este protocolo, la combinación de un inhibidor de la aromatasa y el everolimus no se considerará como quimioterapia citotóxica
    - El tratamiento con agentes biológicos no se considerará como línea previa de tratamiento
    4. Aleatorización anterior en el presente estudio
    5. Tratamiento previo con un inhibidor de PARP (incluido el olaparib) u otro inhibidor de DDR (salvo si dicho tratamiento hubiera tenido menos de 3 semanas de duración y hubieran transcurrido como mínimo 12 meses entre la última dosis y la aleatorización. No podrán participar los pacientes que no hubiesen tolerado el mencionado tratamiento previo)
    6. Exposición a un fármaco en investigación de pequeña molécula en el plazo de los 30 días o de 5 semividas (eligiéndose mayor de estos períodos) antes de la aleatorización. En el caso de la inmunoterapia, el periodo mínimo de lavado deberá ser de 42 días
    7. Pacientes con síndrome mielodisplásico/leucemia mieloide aguda o con signos sugerentes de estas enfermedades
    8. Pacientes con un segundo cáncer primario, con las siguientes EXCEPCIONES: cáncer cutáneo de tipo no melanoma tratado adecuadamente, cáncer in situ de cuello uterino tratado con intención curativa, carcinoma ductal in situ (DCIS), carcinoma de endometrio en estadio 1 Grado 1, u otros tumores sólidos tratados con intención curativa y sin evidencia de enfermedad durante ≥ 5 años antes de entrar en el estudio (incluidos los linfomas [sin afectación de médula ósea])
    9. Valor medio del intervalo QTc corregido mediante la fórmula de Fridericia (QTcF) >470 mseg en mujeres y >450 mseg en hombres (en su cálculo de acuerdo a la práctica del centro) medido en 3 ECG practicados con 2-5 minutos de separación a la entrada en el estudio, o síndrome de QT largo congénito. AZD1775 no debe administrarse a pacientes con antecedentes de Torsades de pointes, a menos que se hayan corregido todos los factores de riesgo que contribuyeron a dicho cuadro. AZD1775 no se ha estudio en pacientes con las arritmias ventriculares o con infarto de miocardio reciente
    10. Cualquiera de las siguientes enfermedades cardíacas, ya sea actualmente o en el plazo de los 6 meses anteriores, de Clase ≥ 2 de la New York Heart Association (NYHA):
    - Angina pectoris inestable
    - Insuficiencia cardiaca congestiva
    - Infarto agudo de miocardio
    - Trastorno de la conducción no controlado con marcapasos o medicación
    - Arritmias ventriculares o supraventriculares importantes (podrán participar los pacientes con fibrilación auricular crónica de frecuencia controlada que no presenten otras anomalías cardiacas)
    11. Empleo concomitante de productos conocidos como inhibidores potentes del citocromo P (CYP) 3A (por ejemplo, itraconazol, telitromicina, claritromicina, inhibidores de la proteasa potenciados con ritonavir o cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) o inhibidores moderados del CYP3A (por ejemplo, ciprofloxacino, eritromicina, diltiazem, fluconazol, verapamilo). Se precisa un periodo de lavado de 2 semanas antes de comenzar con el tratamiento del estudio.
    Paciente que ha recibido tratamiento con fármacos, a obtener con receta o de venta libre en farmacia, o con otros productos conocidos como sustratos sensibles de CYP3A4 o como sustratos de CYP3A4 con índice terapéutico estrecho, o que son inhibidores/inductores potentes de CYP3A4 que no puede suspender en el plazo de 2 semanas antes del Día 1 de tratamiento y mantener así durante el estudio y hasta 2 semanas después de la última dosis del fármaco del estudio.
    Los estudios de transportadores (in vitro) han mostrado que AZD1775 es un inhibidor de la proteína de resistencia al cáncer de mama (BCRP). Los pacientes deben suspender la toma de productos de herbolario 7 días antes de la primera dosis del tratamiento del estudio.
    (...)
    Para una mayor información, véase el protocolo
    E.5 End points
    E.5.1Primary end point(s)
    Study end points are defined for the following patient populations: BRCAm, Non BRCAm HRRm, Non HRRm

    - PFS using BICR according to RECIST 1.1
    - Sensitivity analysis of PFS using Investigator assessments according to RECIST 1.1
    Las variables de evaluación del estudio vienen definidas por las siguientes poblaciones de pacientes: BRCAm, Non BRCAm HRRm, Non HRRm

    - La PFS según la revisión central por un comité independiente desconocedor del tratamiento (Blinded Independent Central Review, BICR) mediante los Response Evaluation Criteria in Solid Tumours (RECIST 1.1)
    - Análisis de sensibilidad de la PFS mediante las evaluaciones del Investigador según RECIST 1.1
    E.5.1.1Timepoint(s) of evaluation of this end point
    Throughout the study
    A lo largo del estudio
    E.5.2Secondary end point(s)
    Study end points are defined per the patient populations

    - PFS and objective response using BICR according to RECIST 1.1
    - Sensitivity analysis of PFS and objective response using Investigator assessments according to RECIST 1.1
    - DoR and tumour change using BICR according to RECIST 1.1
    - Sensitivity analysis of DoR, and tumour change using Investigator assessments according to RECIST 1.1
    - Time to death for any cause
    - Mutation status of HRR pathway genes
    - Cmin ss

    Safety
    - AEs (severity graded by CTCAE v4)
    - laboratory tests (clinical chemistry, haematology and urinalysis)
    - vital signs (pulse and BP)
    - ECG data
    - ECOG PS
    Las variables de evaluación del estudio vienen definidas según las poblaciones de pacientes

    - PFS y Respuesta objetiva según la BICR mediante RECIST 1.1
    - Análisis de sensibilidad de la PFS y de la respuesta objetiva mediante las evaluaciones del Investigador según RECIST 1.1
    - DoR y cambios en el tumor según la BICR mediante RECIST 1.1
    - Análisis de sensibilidad de la DoR y de los cambios del tumor mediante las evaluaciones del Investigador según RECIST 1.1
    - Tiempo hasta la muerte (por cualquier causa)
    - Estado de mutación de los genes de la vía HRR
    - Concentración mínima en estado de equilibrio (Cmin ss)

    Seguridad
    - Acontecimientos adversos (Adverse events, AEs) (clasificados por severidad según los Common Terminology Criteria for Adverse Events [CTCAE] v4)
    - Analítica (bioquímica sérica, hematología y orina)
    - Constantes vitales (pulso y presión arterial (blood pressure [BP])
    - Datos del electrocardiograma (ECG)
    - Estado funcional del Eastern Cooperative Oncology Group (ECOG PS)
    E.5.2.1Timepoint(s) of evaluation of this end point
    Throughout the study
    A lo largo del estudio
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    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) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 EEA90
    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
    Belgium
    Canada
    Czech Republic
    Denmark
    France
    Germany
    Ireland
    Italy
    Korea, Republic of
    Netherlands
    Poland
    Portugal
    Spain
    Taiwan
    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
    LVLS
    última visita del último paciente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months1
    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: 1067
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 33
    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 state84
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 695
    F.4.2.2In the whole clinical trial 1100
    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)
    Treatment at the discretion of the Investigator
    Terapéutica según criterio del Investigador
    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 Decision2018-03-16
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-03-08
    P. End of Trial
    P.End of Trial StatusOngoing
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