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    The EU Clinical Trials Register currently displays   37989   clinical trials with a EudraCT protocol, of which   6231   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2018-002553-30
    Sponsor's Protocol Code Number:EORTC-1745-ETF-BCG
    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:2019-07-26
    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 number2018-002553-30
    A.3Full title of the trial
    A Phase II study of Adjuvant PALbociclib as an Alternative to CHemotherapy in Elderly patientS with high-risk ER+/HER2- early breast cancer (APPALACHES)
    Estudio fase II de terapia adyuvante con palbociclib como alternativa a la quimioterapia en pacientes de edad avanzada con cáncer de mama temprano, ER+/HER2- de alto riesgo (APPALACHES)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Phase II study of post-operative palbociclib as an alternative to chemotherapy in older patients with localized breast cancer at high risk of relapse
    Un estudio de fase II de palbociclib postoperatorio como alternativa a la quimioterapia en pacientes mayores con cáncer de mama localizado con alto riesgo de recaída.
    A.4.1Sponsor's protocol code numberEORTC-1745-ETF-BCG
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03609047
    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 SponsorEuropean Organisation for research and treatment of Cancer
    B.1.3.4CountryBelgium
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportEuropean Organisation for the Research and Treatment of cancer
    B.4.2CountryBelgium
    B.4.1Name of organisation providing supportPfizer
    B.4.2CountryBelgium
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationEuropean Organisation for research and treatment of Cancer
    B.5.2Functional name of contact pointClinical Operations Department
    B.5.3 Address:
    B.5.3.1Street Address83/11 Avenue E. Mounnier
    B.5.3.2Town/ cityBrussels
    B.5.3.3Post code1200
    B.5.3.4CountryBelgium
    B.5.4Telephone number003227741013
    B.5.5Fax number003227727063
    B.5.6E-mailregulatory@eortc.org
    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 Ibrance
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Europe MA EEIG
    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 namePalbociclib
    D.3.2Product code PD-0332991
    D.3.4Pharmaceutical form Capsule, hard
    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 INNPALBOCICLIB
    D.3.9.1CAS number 571190-30-2
    D.3.9.2Current sponsor codePalbociclib
    D.3.9.4EV Substance CodeSUB177204
    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: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The 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 nameDocetaxel
    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 INNDOCETAXEL
    D.3.9.2Current sponsor codedocetaxel
    D.3.9.4EV Substance CodeSUB12492MIG
    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: 3
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The 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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPACLITAXEL
    D.3.9.1CAS number 33069-62-4
    D.3.9.4EV Substance CodeSUB09583MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameDoxorubicin
    D.3.2Product code L01DB01
    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
    D.3.9.1CAS number 23214-92-8
    D.3.9.4EV Substance CodeSUB06391MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameEpirubicin
    D.3.4Pharmaceutical 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 INNEPIRUBICIN HYDROCHLORIDE
    D.3.9.1CAS number 56390-09-1
    D.3.9.4EV Substance CodeSUB01915MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 6
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.5The 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.3.4Pharmaceutical 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.3.9.4EV 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 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 Yes
    D.2.1.1.1Trade name Ibrance
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Europe MA EEIG
    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 namePalbociclib
    D.3.2Product code PD-0332991
    D.3.4Pharmaceutical form Capsule, hard
    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 INNPALBOCICLIB
    D.3.9.1CAS number 571190-30-2
    D.3.9.2Current sponsor codePalbociclib
    D.3.9.4EV Substance CodeSUB177204
    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: 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 Ibrance
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Europe MA EEIG
    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 namePalbociclib
    D.3.2Product code PD-0332991
    D.3.4Pharmaceutical form Capsule, hard
    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 INNPALBOCICLIB
    D.3.9.1CAS number 571190-30-2
    D.3.9.2Current sponsor codePalbociclib
    D.3.9.4EV Substance CodeSUB177204
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number125
    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
    Localized ER+ breast cancer
    Cáncer de mama ER+ localizado
    E.1.1.1Medical condition in easily understood language
    Localized breast cancer that is also found to be sensitive to anti-hormonal therapy. Before inclusion in the study; tumor should have been recently and completely removed surgically.
    Cáncer de mama localizado que también es sensible a la terapia antihormonal. Antes de la inclusión en el estudio, el tumor debe haber sido extirpado quirúrgicamente de forma reciente y completa.
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level LLT
    E.1.2Classification code 10070575
    E.1.2Term Estrogen receptor positive breast cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10070577
    E.1.2Term Oestrogen receptor positive breast cancer
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLT
    E.1.2Classification code 10006290
    E.1.2Term Breast and nipple neoplasms malignant
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLGT
    E.1.2Classification code 10006291
    E.1.2Term Breast neoplasms malignant and unspecified (incl nipple)
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level SOC
    E.1.2Classification code 10029104
    E.1.2Term Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    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
    The primary objective of this trial is to assess the efficacy of the combination of at least 5 year endocrine therapy and 2 year-palbociclib as adjuvant systemic treatment instead of adjuvant chemotherapy followed by endocrine therapy in older patients with stage II-III ER+/HER2- early breast cancer.
    El objetivo principal de este ensayo es evaluar la eficacia de la combinación de hormonoterapia durante al menos 5 años y palbociclib durante 2 años como tratamiento sistémico complementario en lugar de quimioterapia complementaria seguida de hormonoterapia en pacientes de edad avanzada con cáncer de mama temprano RE+/HER2- en estadio II-III.
    E.2.2Secondary objectives of the trial
    - To evaluate the efficacy with respect to different time-to-event endpoints (distant recurrence-free interval (DRFI), breast cancer specific survival (BCSS), OS) at 3, 6 and 10 years in both arms
    - To evaluate toxicity in both arms
    - To evaluate the treatment discontinuation and dose reduction rates in both arms
    - To assess the reasons for treatment discontinuation
    - To evaluate completion of oral therapy in the experimental arm
    - To assess the evolution of Health-Related Quality of Life (HRQoL) in both arms
    - To assess the evolution, prognostic and predictive effects of geriatric assessment in both arms
    - Evaluar la eficacia con respecto a los distintos criterios de valoración de tiempo transcurrido hasta el acontecimiento (intervalo sin recurrencia a distancia [ISRD], supervivencia específica para el cáncer de mama [SECM], SG) a los 3, 6 y 10 años en ambos grupos.
    - Evaluar la toxicidad en ambos grupos.
    - Evaluar las tasas de interrupción del tratamiento y de reducción de la dosis en ambos grupos.
    - Evaluar los motivos de la interrupción del tratamiento.
    - Evaluar la conclusión del tratamiento por vía oral en el grupo experimental.
    - Evaluar la evolución de la calidad de vida relacionada con la salud (CdVRS) en ambos grupos.
    - Evaluar la evolución y los efectos pronóstico y predictivo de la evaluación geriátrica en ambos grupos.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Women or men with stage II or stage III, early invasive breast cancer according to the UICC 8th edition for TNM classification
    - Histologically confirmed ER+ , HER-2 negative, early invasive breast cancer based on results of local pathology. Testing may be performed on
    diagnostic core biopsy or resection specimen.
    - In patients with multicentric, multifocal and/or bilateral breast cancer, all histopathologically examined invasive tumors must meet pathologic
    criteria regarding ER and HER2-status described above.
    - Adjuvant chemotherapy indicated and feasible according to treating physician and patient, based on standard clinicopathological parameters
    (tumor size, lymph node involvement, general health status, proliferation marker, patient wish) and gene expression profile if available.
    - Adjuvant chemotherapy with both anthracycline and taxanes (in combination or in sequence) considered not indicated or not feasible according to treating physician.
    - Age ≥70 years
    - WHO Performance status 0-2
    - Completed G8 geriatric assessment within 3 weeks of randomization.
    - Participation in translational research is mandatory and therefore patient must consent for it. Patient should allow sequential sampling of blood during the course of the trial
    - Patient must have undergone breast +/- axillary surgery with curative intent for the current malignancy ≤8 weeks before randomization. The
    final primary tumor surgical specimen must have R0 margins free from tumor.
    - Patients must have sufficient resolution of any surgical side effects from the last surgery per physician assessment, with no active wound
    healing complications at the time of randomization.
    - Incentive to undergo adjuvant radiation therapy when indicated per local institutional guidelines.
    Note: For patients in the palbociclib arm, radiation therapy when indicated has to start ≤9 weeks after last surgery. The endocrine therapy can be initiated during or after the radiation therapy but not later than 3 weeks after the last radiotherapy. Palbociclib has to start ≤3 weeks after the last radiotherapy. When radiation therapy is not indicated, endocrine
    therapy and palbociclib have to be initiated ≤9 weeks after last surgery.
    Note: For patients in the chemotherapy arm, chemotherapy has to be the first adjuvant treatment and has to start ≤9 weeks after the last surgery.
    When radiation therapy is indicated, this treatment has to start ≤6 weeks after the last chemotherapy administration. Adjuvant endocrine therapy can be initiated during or after the radiation therapy but not
    later than 3 weeks after the last radiotherapy. When radiation therapy is not indicated, endocrine therapy has to be initiated ≤6 weeks after last
    chemotherapy administration.
    - Adequate baseline organ function, evidenced by the following laboratory results within 3 weeks of randomization:
    - Hemoglobin ≥ 9 g/dL
    - Absolute neutrophil count (ANC) ≥ 1500/mm3
    - Platelet count ≥ 100,000/mm3
    - Total bilirubin ≤ 1.5 upper limit of normal (ULN), or total bilirubin ≤ 3.0 × ULN in patients with documented Gilbert's Syndrome.
    - Glomerular Filtration Rate (GFR) ≥ 30 ml/min according to MDRD formula or CKD-EPI formula or Cockcroft and Gault formula
    - SGOT (AST), SGPT (ALT) and alkaline phosphatase ≤ 2.5 × ULN
    - Patients must be able and willing to swallow and retain oral medication without a condition that would interfere with enteric absorption.
    - For men participating in the trial:
    • As fertility may be affected permanently with protocol treatment, we advise offering to patient sperm preservation prior to treatment.
    • Patient with partner of childbearing / reproductive potential should use two birth control methods, as defined by the investigator, from the time of signing the informed consent form , and throughout the entire study and for 6 months after the last dose of chemotherapies or 3 months and half (14 weeks) after last dose of palbociclib. Two (2) of the following barrier methods in combination are allowed during the study.
    It is strongly recommended that at least one of these two methods be highly effective. A highly effective contraceptive method is one that has a failure rate of less than 1% and does not interfere with the proposed investigations.
    Highly effective methods: Intra-uterine devices (IUD) or Hormonal (birth control pills/oral contraceptives, injectable contraceptives, contraceptive patches, or contraceptive implants)
    Other effective methods (barrier methods): Latex condom or Diaphragm with spermicide; Cervical cap; Sponge
    If one of the highly effective methods cannot be used, using two other effective methods at the same time is required.
    Birth control methods as directed above must be used unless patient completely avoid having heterosexual intercourse.
    Note: for sexual abstinence: occasional abstinence, the rhythm method and the withdrawal method are not acceptable methods of contraception.
    - Signed, written informed consent.
    - Mujeres u hombres con cáncer de mama invasivo temprano en estadio II o III conforme a la 8.ª edición de la clasificación TNM de la UICC.
    -Cáncer de mama invasivo temprano RE+ (al menos el 10 % de células con tinción positiva para RE) y HER2 negativo confirmado mediante histología con base en los resultados de anatomopatología local Las pruebas pueden realizarse en muestras obtenidas mediante biopsia diagnóstica con aguja gruesa o en muestras extirpadas.
    - En los pacientes con cáncer de mama multicéntrico, multifocal y/o bilateral, todos los tumores invasivos que se examinaron mediante histopatología deben cumplir los criterios anatomopatológicos en relación con el estado de RE y HER2 descrito antes.
    - Basándose en los parámetros clinicopatológicos estándar (tamaño del tumor, afectación de los ganglios linfáticos, estado de salud general, marcadores de proliferación, deseos del paciente) y el perfil de expresión génica, si está disponible, la quimioterapia complementaria está indicada y es viable de acuerdo con el médico responsable del tratamiento y el paciente.
    - La quimioterapia complementaria con antraciclinas y taxanos (en combinación o en secuencia) no se considera indicada o no es viable de acuerdo con el médico responsable del tratamiento.
    - Edad ≥ 70 años.
    - Estado general 0-2 según la OMS.
    - Haber completado la valoración geriátrica G8 en las 3 semanas anteriores a la aleatorización.
    - La participación en la investigación traslacional es obligatoria y, por lo tanto, el paciente debe dar su consentimiento para ello. El paciente debe permitir la obtención de muestras secuenciales de sangre durante el transcurso del ensayo.
    - El paciente debe haberse sometido a cirugía de mama +/- axilar con intención curativa para la neoplasia maligna actual ≤ 8 semanas antes de la aleatorización. La muestra quirúrgica del tumor primario final debe presentar bordes R0 sin afectación tumoral.
    - Los pacientes deben presentar, conforme a la valoración del médico, suficiente resolución de cualquier efecto secundario de la última intervención quirúrgica y carecer de complicaciones en la cicatrización de las heridas activas en el momento de la aleatorización.
    - Incentivo para recibir radioterapia complementaria cuando esté indicado por las directrices institucionales locales.
    - Nota: en el caso de los pacientes en el grupo de palbociclib, la radioterapia, cuando esté indicada, deberá empezar ≤ 9 semanas después de la última intervención quirúrgica. La hormonoterapia puede iniciarse durante o después de la radioterapia, pero como máximo 3 semanas después de la última administración de radioterapia. El palbociclib debe empezar ≤ 3 semanas después de la última administración de radioterapia. Cuando la radioterapia no está indicada, la hormonoterapia y el palbociclib deberán iniciarse ≤ 9 semanas después de la última intervención quirúrgica.
    - Nota: en el caso de los pacientes en el grupo de quimioterapia, esta debe ser el primer tratamiento complementario y debe empezar ≤ 9 semanas después de la última intervención quirúrgica. Cuando esté indicada la radioterapia, este tratamiento deberá comenzar ≤ 6 semanas después de la última administración de quimioterapia. La hormonoterapia complementaria puede iniciarse durante o después de la radioterapia, pero como máximo 3 semanas después de la última administración de radioterapia. Cuando no esté indicada la radioterapia, la hormonoterapia deberá comenzar ≤ 6 semanas después de la última administración de quimioterapia.
    - Función orgánica inicial adecuada, demostrada mediante los siguientes resultados analíticos en las 3 semanas anteriores a la aleatorización:
    - Hemoglobina ≥9 g/dl.
    - Recuento absoluto de neutrófilos (RAN) ≥ 1500/mm3.
    - Cantidad de plaquetas ≥100 000/mm3.
    - Bilirrubina total ≤ 1,5 veces el límite superior de la normalidad (LSN) o bilirrubina total ≤ 3,0 × LSN en pacientes con síndrome de Gilbert documentado.
    - Tasa de filtración glomerular (TFG) ≥ 30 ml/min de acuerdo con la fórmula MDRD, la fórmula CKD-EPI o la fórmula de Cockcroft y Gault
    - SGOT (ALT), SGPT (AST) y fosfatasa alcalina ≤ 2,5 × LSN.
    - Los pacientes deben ser capaces y estar dispuestos a tragar y retener medicamentos por vía oral y no presentar ninguna afección que pudiera interferir con la absorción intestinal.
    - Para los hombres que participan en el ensayo:
    • Dado que la fertilidad puede verse afectada de forma permanente, recomendamos conservación de esperma antes del tratamiento.
    • Los pacientes con pareja en edad fértil/con capacidad reproductiva deben utilizar dos métodos anticonceptivos, según los defina el investigador, Dos (2) de los siguientes métodos de barrera combinados están permitidos durante el estudio:
    Métodos altamente eficaces: Dispositivos intrauterinos o Hormonales.
    Otros métodos eficaces: Preservativo de látex o Diafragma con espermicida, capuchón cervicouterino, esponja.
    - Consentimiento informado por escrito firmado.
    E.4Principal exclusion criteria
    - Evidence of macroscopic distant metastases, investigated according to local institutional guidelines.
    - Previous history of invasive breast cancer
    - Patients who received treatment with live vaccines within 30 days prior the first dose of study medication.
    - Systemic anticancer therapy prior to the breast cancer surgery
    - Prior therapy with any CDK4/6 inhibitor
    - Concurrent investigational agent within 28 days of randomization
    - Concomitant anticancer treatment with the exception of bone
    antiresorptive agents or LHRH agonists in male patients treated with an aromatase-inhibitor
    - History of allergic reactions attributed to compounds of chemical or biological composition similar to palbociclib or to chemotherapy components
    - Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
    - Medications or substances that are potent inhibitors or inducers of CYP3A isoenzymes within 7 days of randomization
    - Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (including known HIV, active hepatitis B and/or hepatitis C infection), symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or uncontrolled diabetes.
    Note: For patients for whom doxorubicin or epirubicin is planned, an adequate baseline cardiac function (left ventricular ejection fraction ≥
    50%) should have been proven no more than 1 year before treatment start.
    - Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up
    schedule; those conditions should be discussed with the patient before registration in the trial
    - Other malignancy within the last 5 years except: adequately treated non-metastatic non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ of the breast.
    - Signos de metástasis macroscópicas a distancia, investigados de acuerdo con las directrices locales institucionales.
    - Antecedentes de cáncer de mama invasivo.
    - Pacientes que hayan recibido tratamiento con vacunas vivas en los 30 días anteriores a la administración de la primera dosis de la medicación del estudio.
    - Tratamiento antineoplásico sistémico antes de la intervención quirúrgica por cáncer de mama.
    - Tratamiento anterior con algún inhibidor de CDK4/6.
    - Administración concurrente de fármacos en investigación en los 28 días anteriores a la aleatorización.
    - Tratamiento antineoplásico concomitante a excepción de agentes anti-reabsorción ósea o agonistas de la LHRH en pacientes varones tratados con un inhibidor de la aromatasa.
    - Antecedentes de reacciones alérgicas atribuidas a compuestos de composición química o biológica similares a los de palbociclib o a componentes de la quimioterapia.
    - Pacientes con problemas hereditarios raros de intolerancia a la galactosa, deficiencia de lactasa Lapp o malabsorción de glucosa-galactosa.
    - Medicamentos o sustancias que sean inhibidores o inductores potentes de las isoenzimas de CYP3A en los 7 días anteriores a la aleatorización.
    - Enfermedades intercurrentes no controladas incluyendo, entre otras, infección activa o en curso (incluyendo infección conocida por VIH, hepatitis B y/o C activa), insuficiencia cardíaca congestiva sintomática, angina de pecho inestable, arritmia cardíaca no controlada o diabetes no controlada.
    - Nota: en el caso de los pacientes para los cuales se prevé utilizar doxorrubicina o epirrubicina, debe haberse demostrado una función cardíaca inicial adecuada (fracción de eyección del ventrículo izquierdo ≥ 50 %) como máximo 1 año antes del inicio del tratamiento.
    - Cualquier afección psicológica o situación familiar, sociológica o geográfica que pudiera potencialmente dificultar el cumplimiento del protocolo del estudio y el calendario de seguimiento; estas situaciones deben comentarse con el paciente antes del registro en el ensayo.
    - Otra neoplasia maligna en los 5 años anteriores, a excepción de: cáncer de piel no melanómico no metastásico que haya recibido tratamiento adecuado, cáncer cervicouterino in situ que se haya tratado con intención curativa, carcinoma ductal in situ de la mama.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint in this study is the 3-year distant recurrence-free interval rate in the experimental arm.
    El criterio de valoración principal de la eficacia: tasa de intervalo sin recurrencia a distancia (ISRD) a los 3 años en el grupo experimental.
    E.5.1.1Timepoint(s) of evaluation of this end point
    3 years (main analysis), 6 and 10 years (long-term analyses)
    3 años (análisis principal), 6 y 10 años (análisis a largo plazo)
    E.5.2Secondary end point(s)
    - Distant recurrence-free interval at 3 years in the control arm and at 6 and 10 years in both arms.
    - Breast cancer specific survival at 3, 6, and 10 years in both arms.
    - Overall survival at 3, 6 and 10 years in both arms.
    - Adverse events according to CTCAE v5.0 recorded at every patient visit in both arms.
    - Treatment discontinuation and dose reduction rates in both arms.
    - Reason for treatment discontinuation.
    - HRQoL questionnaires (modified QLQ-C30, ELD-14, and selected items from the BR45 module) at 3 months, 6 months, 1 year, 2 years, and 3 years in both arms.
    - Geriatric assessment tools (G8, iADL, ADL, Gait speed, CCI, social situation) at 3 months, 6 months, 1 year, 2 years, and 3 years in both arms.
    - Intervalo libre de recidivas a 3 años en el grupo de control y a 6 y 10 años en ambos grupos.
    - Supervivencia específica al cáncer de mama a los 3, 6 y 10 años en ambos grupos.
    - Supervivencia global a los 3, 6 y 10 años en ambos grupos.
    - Eventos adversos según CTCAE v5.0 registrados en cada visita del paciente en ambos grupos.
    - Interrupción del tratamiento y tasas de reducción de dosis en ambos grupos.
    - Motivo de la interrupción del tratamiento.
    - Cuestionarios de calidad de vida (QLQ-C30 modificada, ELD-14 y preguntas específicas de BR45) a los 3 meses, 6 meses, 1 año, 2 años y 3 años en ambos grupos.
    - Herramientas de evaluación geriátrica (G8, AVDi, AVD, velocidad de marcha, ICC, situación social) a los 3 meses, 6 meses, 1 año, 2 años y 3 años en ambos grupos.
    E.5.2.1Timepoint(s) of evaluation of this end point
    3 years (main analysis), 6 and 10 years (long-term analyses)
    3 años (análisis principal), 6 y 10 años (análisis a largo plazo)
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) 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 No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned14
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA80
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    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
    End of study occurs when all of the following criteria have been satisfied:
    1. Thirty days after all patients have stopped protocol treatment (palbociclib or chemotherapy)
    2. The trial is mature for the analysis of the primary endpoint as defined in the protocol
    3. The database has been fully cleaned and frozen for this analysis
    El final del estudio ocurre cuando todos los siguientes criterios han sido satisfechos:
    1. Treinta días después de que todos los pacientes hayan interrumpido el tratamiento de protocolo (palbociclib o quimioterapia)
    2. El ensayo está maduro para el análisis de la variable principal de evaluación según se define en el protocolo.
    3. La base de datos ha sido completamente limpiada y congelada para este análisis.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years12
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years12
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In 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) No
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 366
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 366
    F.4.2.2In the whole clinical trial 366
    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)
    The treatment will be left to the discretion of the treating physician.
    El tratamiento se dejará a la discreción del médico tratante.
    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 Decision2019-09-27
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-09-20
    P. End of Trial
    P.End of Trial StatusOngoing
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