Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

  • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).


    The EU Clinical Trials Register currently displays   43935   clinical trials with a EudraCT protocol, of which   7309   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2021-002027-38
    Sponsor's Protocol Code Number:SOLTI2101
    National Competent Authority:Portugal - INFARMED
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-06-29
    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 ConcernedPortugal - INFARMED
    A.2EudraCT number2021-002027-38
    A.3Full title of the trial
    A Phase III, multicenter, open-label study of ribociclib vs. palbociclib in patients with advanced hormone receptor-positive/HER2-negative/HER2-Enriched breast cancer - HARMONIA trial
    Estudo de Fase III, multicêntrico, aberto, de ribociclib em comparação com palbociclib em doentes com cancro da mama avançado positivo para o recetor hormonal/HER2-negativo/HER2-enriquecido - ensaio HARMONIA
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Comparative study of ribociclib and palbociclib in patients with advanced hormone receptor-positive/HER2-negative/HER2-Enriched breast cancer - HARMONIA trial
    Estudo comparativo de ribociclib e palbociclib em doentes com cancro da mama avançado com receptores hormonais positivos/HER2-negativo/HER2 enriquecido - ensaio HARMONIA
    A.3.2Name or abbreviated title of the trial where available
    HARMONIA
    A.4.1Sponsor's protocol code numberSOLTI2101
    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 SponsorSOLTI
    B.1.3.4CountrySpain
    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 supportNOVARTIS PHARMA AG
    B.4.2CountrySwitzerland
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSOLTI
    B.5.2Functional name of contact pointAREA DE INVESTIGACION CLINICA
    B.5.3 Address:
    B.5.3.1Street AddressBalmes, 89, 1st floor, modulo 2
    B.5.3.2Town/ cityBarcelona
    B.5.3.3Post code08008
    B.5.3.4CountrySpain
    B.5.4Telephone number34933436302
    B.5.6E-mailregsolti@gruposolti.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 KISQALI 200 MG
    D.2.1.1.2Name of the Marketing Authorisation holderNovartis Europharm Limited
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameRibociclib
    D.3.2Product code LEE011
    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 INNRibociclib
    D.3.9.1CAS number -
    D.3.9.2Current sponsor codeLEE011
    D.3.9.3Other descriptive nameRIBOCICLIB SUCCINATE
    D.3.9.4EV Substance CodeSUB184164
    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.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name IBRANCE 75 MG
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Europe MA EEIG
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 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 INNPalbociclib
    D.3.9.1CAS number -
    D.3.9.2Current sponsor codePD-0332991
    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: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name IBRANCE 100 MG
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Europe MA EEIG
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 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 INNPalbociclib
    D.3.9.1CAS number -
    D.3.9.2Current sponsor codePD-0332991
    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: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name IBRANCE 125 MG
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer Europe MA EEIG
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 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 INNPalbociclib
    D.3.9.1CAS number -
    D.3.9.2Current sponsor codePD-0332991
    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.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 nameTislelizumab
    D.3.2Product code BGB-A317
    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 INNTISLELIZUMAB
    D.3.9.1CAS number -
    D.3.9.3Other descriptive nameBGB-A317
    D.3.9.4EV Substance CodeSUB193656
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients with advanced hormone receptor-positive/HER2-negative/HER2-Enriched breast cancer
    Doentes com cancro da mama avançado com recetor hormonal positivo/HER2-negativo/ enriquecido com HER2
    E.1.1.1Medical condition in easily understood language
    Advanced hormone receptor-positive/HER2-negative/HER2-Enriched breast cancer
    Cancro da mama avançado com recetor hormonal positivo/HER2-negativo/ enriquecido com HER2
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare PFS of ribociclib plus endocrine therapy over palbociclib plus endocrine therapy with respect to PFS in patients with advanced hormone receptor-positive, HER2-negative and HER2-E breast cancer.
    Comparar a PFS do tratamento com ribociclib e terapêutica endócrina com a do tratamento com palbociclib e terapêutica endócrina em participantes com cancro da mama avançado positivo para o recetor hormonal, HER2-negativo, HER2-E.
    E.2.2Secondary objectives of the trial
    •To compare the two treatment arms with respect to Progression on next-line therapy (PFS2) in the HER2-E cohort
    •To compare the two treatment arms with respect to overall survival in the HER2-E cohort
    •To evaluate the two treatment arms with respect to overall response rate (ORR) and clinical benefit rate (CBR) in the HER2-E cohort.
    •To describe time to response and duration of response in each treatment arm in the HER2-E cohort.
    •To evaluate the safety and tolerability of ribociclib and palbociclib in combination with endocrine therapy in the HER2-E cohort
    •To evaluate patient reported outcomes for health-related quality of life in the two treatment arms of the HER2-E cohort.
    * Comparar a PFS2 nos dois braços de tratamento na coorte HER2-E.
    * Comparar a sobrevivência global nos dois braços de tratamento na coorte HER2-E.
    * Avaliar a taxa de resposta global (ORR) e a taxa de benefício clínico (CBR) nos dois braços de tratamento em participantes com HER2-E.
    * Descrever o tempo até à resposta e a duração da resposta em cada braço de tratamento na coorte HER2-E.
    * Avaliar a segurança e tolerância do ribociclib e palbociclib em combinação com a terapêutica endócrina na coorte HER2-E.
    * Avaliar os resultados comunicados pelos participantes em termos de qualidade de vida relacionada com a saúde nos dois braços de tratamento na coorte HER2-E.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Signed informed consent must be obtained prior to any trial-specific screening procedure. Signed informed molecular pre-screening consent must be obtained prior to PAM50 test.
    2. Male/female patients ≥18 years of age
    3. HR-positive and HER2-negative breast cancer by local testing
    4. ECOG performance status of 0 to 1.
    5. Prior radiation therapy for metastatic disease is permitted. Patients must have recovered from radiotherapy toxicities prior to inclusion.
    6. Patient has advanced (loco regionally recurrent not amenable to curative therapy or metastatic) breast cancer.
    7. Availability of FFPE tumor block for biomarker analysis, obtained during metastatic period.
    8. HER2-E or Basal-like subtype as per central PAM50 analysis.
    9. Measurable disease or non-measurable (but evaluable), as defined by RECIST v1.1.
    10. Adequate hematologic and end-organ function
    11. Patient must be willing and able to comply with scheduled visits, treatment plans, laboratory tests, and other trial procedures.
    12. Women of childbearing potential must have confirmed negative serum pregnancy test.
    13. Women of CBP must be willing to use highly effective methods of contraception.
    14. Postmenopausal OR Pre/perimenopausal status as defined in protocol
    15. Patients must have the ability to swallow oral medication.
    16. Patient must have a 6-lead or 12-lead ECG at screening
    For Basal-like cohort only:
    17.Non-sterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of tislelizumab
    - A sterile male is defined as one for whom azoospermia has been previously demonstrated in a semen sample examination as definitive evidence of infertility.
    - Males with known "low sperm counts" (consistent with "sub-fertility") are not to be considered sterile for purposes of this study.
    1. Deve ser obtido o consentimento informado assinado antes de qualquer procedimento de seleção específico do ensaio. Deve ser obtido o consentimento informado assinado para testes moleculares de seleção antes da realização do teste PAM50.
    2. Os participantes de ambos os géneros terão de ter, no mínimo, 18 anos de idade no dia de assinatura do consentimento informado.
    3. Cancro da mama HR-positivo e HER2-negativo documentado histologicamente com testes a nível local.
    4. Ter um valor na escala de desempenho do Eastern Cooperative Oncology Group (ECOG) de 0 a 1.
    5. É permitida a inclusão de participantes que tenham feito radioterapia prévia para doença metastática. É necessário que os participantes tenham recuperado das toxicidades da radioterapia antes da inclusão.
    6. O participante apresenta cancro da mama avançado (com recidiva locorregional, não passível de terapêutica curativa ou metastático).
    7. Disponibilidade de bloco tumoral FFPE para análise de biomarcadores, colhido durante o período metastático.
    8. Subtipo HER2-E ou basal por análise central PAM50.
    9. Ter doença mensurável ou doença não mensurável (mas avaliável), conforme definido pelos RECIST, vs 1.1.
    10. Ter função hematológica e de órgãos vitais adequada.
    11. O participante deve estar disposto a realizar e ser capaz de cumprir as visitas agendadas, planos de tratamento, análises laboratoriais e outros procedimentos do ensaio.
    12. As mulheres férteis devem ter um teste de gravidez serológico negativo.
    13. As mulheres férteis devem estar dispostas a utilizar métodos contracetivos extremamente eficazes.
    14. Pós-menopausa OU estado pré/perimenopausa, tal como definido no protocolo.
    15. Os participantes devem ter a capacidade de engolir a medicação tomada por via oral.
    16.O participante deve ter um ECG de 6 derivações ou de 12 derivações.
    Apenas para a coorte Basal-Like:
    17. Homens não estéreis devem estar dispostos a usar um método anticoncepcional altamente eficaz durante o estudo e por ≥ 120 dias após a última dose de tislelizumab
    o Um homem estéril é definido como aquele para quem a azoospermia foi previamente demonstrada em um exame de amostra de sémen como evidência definitiva de infertilidade.
    o Homens com “baixa contagem de esperma” conhecida (consistente com “subfertilidade”) não devem ser considerados estéreis para os propósitos deste estudo.


    E.4Principal exclusion criteria
    1. Prior therapy with any CDK4/6 inhibitors.
    2. Patient has received prior treatment with chemotherapy for advanced / metastatic breast cancer (neoadjuvant/ adjuvant chemotherapy for early breast cancer is allowed).
    3. Patient has received extended-field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to enrollment and has not recovered to grade 1 or better from related side effects of such therapy. Patients in whom ≥ 25% of the bone marrow has been previously irradiated are also excluded.
    4. Any ongoing acute toxic effects of prior anti-cancer therapy or major surgical procedures to NCI CTCAE version 4.03 Grade ≤ 1 at day of inclusion.
    5. Uncontrolled pleural effusion, pericardial effusion, or ascites.
    6. Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
    7. Known active central nervous system metastases and/or carcinomatous meningitis.
    8. Known history of Human Immunodeficiency Virus (HIV).
    9. Patient has known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
    10. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality
    11. Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator’s judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol or limit life expectancy to ≤6 months.
    12. Participation in other studies involving investigational drug(s) within 30 days prior to randomization or within 5 half-lives of the investigational drug(s)
    13. Pregnant or breast-feeding women or women who plan to become pregnant or breast-feed during the trial.
    14. Not able to understand and to comply with study instructions and requirements according to investigator criteria.
    15.Patient is currently receiving or has received systemic corticosteroids (>10 mg daily of prednisone or equivalent) ≤ 2 weeks prior to starting trial treatment, or has not fully recovered from side effects of such treatment.

    For HER2-E cohort only:
    16. Patient with a known hypersensitivity to any of the excipients of ribociclib, palbociclib and/or endocrine therapy
    17. Patient is currently receiving any protocol-prohibited substances within 7 days before randomization
    18. Patient has impairment of GI function or GI disease that may significantly alter the absorption of the oral trial treatments
    For Basal-like cohort only:
    19. History of hypersensitivity reactions to paclitaxel or other drugs formulated in the same solvent as paclitaxel (polyoxyethylated castor oil).
    20.A history of severe hypersensitivity reactions to other monoclonal antibodies.
    21.Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways.
    22.Active autoimmune diseases or history of autoimmune diseases that may relapse. (refer to Appendix 3 for a list of conditions).
    23.History of interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases, etc. Patients with significantly impaired pulmonary function, or who require supplemental oxygen at baseline must undergo an assessment of pulmonary function at screening.
    24. Infection (including tuberculosis infection, etc.) requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to first dose of study drugs.
    25.Prior allogeneic stem cell transplantation or organ transplantation.
    26.Was administered a live vaccine ≤ 28 days before first dose of study drug.
    1. Terapêutica prévia com quaisquer inibidores da CDK4/6.
    2. Participantes que realizaram tratamento prévio de quimioterapia para cancro da mama avançado/metastático (permitida quimioterapia neoadjuvante/adjuvante para cancro da mama em fase precoce).
    3. Participantes que realizaram radioterapia com irradiação de campos extensos durante ≤4 semanas ou com irradiação de campos limitados durante ≤2 semanas antes da inclusão e que não recuperaram dos efeitos secundários relacionados com a radioterapia para grau 1 ou inferior (exceto alopecia ou outras toxicidades que não sejam consideradas um risco de segurança para o participante a critério do investigador). Os participantes com irradiação prévia de ≥25% da medula óssea também estão excluídos.
    4. Participantes com toxicidades não resolvidas de terapia anticancerígena anterior ou de grandes procedimentos cirúrgicos prévios, que não estejam resolvidos com pelo menos grau ≤1 de acordo com os CTCAE do NCI, versão 4.03, no dia da inclusão.
    5. Ter derrame pleural não controlado, derrame pericárdico ou ascite.
    6. Ter uma doença maligna adicional conhecida que esteja a progredir ou tenha exigido tratamento ativo nos últimos 3 anos.
    7. Metástases ativas conhecidas ao nível do sistema nervoso central e/ou meningite carcinomatosa.
    8. Historial conhecido de infeção pelo vírus da imunodeficiência humana (VIH).
    9. O participante apresenta uma infeção conhecida ativa pelo vírus da hepatite B (VHB) ou pelo vírus da hepatite C (VHC).
    10. Doença cardíaca não controlada clinicamente significativa e/ou anomalia a nível da repolarização cardíaca.
    11. O participante apresenta qualquer outra doença grave e/ou não controlada concomitante que poderia, a critério do Investigador, causar riscos de segurança inaceitáveis, contraindicar a participação do participante no ensaio clínico ou comprometer a adesão ao protocolo (por exemplo, pancreatite crónica, hepatite crónica ativa, cirrose hepática ou qualquer outra doença hepática significativa, infeções fúngicas, bacterianas ou virais não tratadas ou não controladas ativas, infeção ativa que exija terapêutica antibacteriana sistémica, etc.) ou limitar a esperança de vida a ≤6 meses.
    12. Participação em outros estudos que envolvam medicamento(s) experimental(ais) até 30 dias antes da aleatorização ou até 5 semividas do(s) medicamento(s) experimental(ais).
    13. Mulheres grávidas ou a amamentar ou mulheres que planeiam engravidar ou amamentar durante o ensaio.
    14. Não ser capaz de compreender e cumprir as instruções e requisitos do estudo, a critério do investigador.
    15. Participante que está atualmente a receber ou que recebeu corticosteroides sistémicos (>10 mg diários de prednisona ou equivalente) ≤ 2 semanas antes do início do tratamento experimental ou não se recuperou totalmente dos efeitos adversos desse tratamento.
    Apenas para a coorte HER2-E:
    16. Participante com hipersensibilidade conhecida a qualquer um dos excipientes do ribociclib, palbociclib e/ou terapêutica endócrina.
    17. O participante estar atualmente a receber qualquer uma das seguintes substâncias até 7 dias antes da aleatorização.
    18. O participante apresentar uma insuficiência da função GI ou uma doença GI que possa alterar significativamente a absorção dos tratamentos administrados por via oral do ensaio.
    Apenas para a coorte basal:
    19. Historial de reações de hipersensibilidade ao paclitaxel ou a outros medicamentos cuja formulação inclui o mesmo solvente que o paclitaxel (óleo de rícino polioxietilado).
    20. História de reações graves de hipersensibilidade a outros anticorpos monoclonais.
    21. Terapia prévia com um anti-PD-1, anti-PD-L1, anti-PD-L2 ou qualquer outro anticorpo ou medicamento direcionado especificamente à co-estimulação de células T ou vias de checkpoint.
    22. Doenças autoimunes ativas ou história de doenças autoimunes que podem recidivar.(consulte o Apêndice 3 para consultar a lista de condições).
    23. História de doença pulmonar intersticial, pneumonite não infecciosa ou doenças pulmonares não controladas, incluindo fibrose pulmonar, doenças pulmonares agudas, etc. Participantes com função pulmonar significativamente comprometida ou que necessitam de oxigênio suplementar no início do estudo devem ser submetidos a uma avaliação da função pulmonar no screening.
    24. Infecção (incluindo infecção por tuberculose, etc.) que requer terapia antibacteriana, antifúngica ou antiviral sistêmica dentro de 14 dias antes da primeira dose dos medicamentos do estudo.
    25. Transplante alogênico prévio de células-tronco ou transplante de órgãos
    26. Participantes que receberam a administração de uma vacina viva ≤ 28 dias antes da primeira dose do medicamento do estudo.
    E.5 End points
    E.5.1Primary end point(s)
    Progression-free survival using RECIST 1.1 criteria, as assessed by local radiologists/investigators
    Sobrevivência livre de progressão utilizando os critérios RECIST 1.1, conforme avaliado por radiologistas/investigadores locais
    E.5.1.1Timepoint(s) of evaluation of this end point
    Image testing will be done mandatory, every 8 weeks (+/- 7 days) for the first 12 months, then every 12 weeks (+/- 7 days)
    Os testes de imagem serão efectuados obrigatoriamente, de 8 em 8 semanas (+/- 7 dias) durante os primeiros 12 meses, e depois de 12 em 12 semanas (+/- 7 dias)
    E.5.2Secondary end point(s)
    PFS2, defined as the time from randomization to first documented progression on next-line therapy or death, whichever occurs first
    OS
    Overall response and clinical benefit as defined by RECIST 1.1.
    Time to response and duration of response per RECIST 1.1
    Occurrence /severity of AEs, laboratory abnormalities, discontinuation rates, dose reductions/interruptions

    Time to 10% deterioration in the global health status/QOL scale score of the EORTC QLQ-C30
    Change from baseline in the global health status/QOL scale score of the EORTC QLQ-C30
    Change from baseline in the fatigue scale score of the FACT-G score of FACIT Fatigue Scale (Version 4)
    E.5.2.1Timepoint(s) of evaluation of this end point
    1.Follow up for PFS2 and OS will be every 6 months
    2.Image testing will be done mandatory, every 8 weeks (+/- 7 days) for the first 12 months, then every 12 weeks (+/- 7 days)
    3.Safety (incidence of AEs) will be monitored continuously, until 30 days after discontinuation
    4.Patient reported outcomes will be done every two cycles for the first 12 months, then every three cycles
    1. o acompanhamento para PFS2 e OS será efectuado de 6 em 6 meses
    2. os testes de imagem serão efectuados obrigatoriamente, de 8 em 8 semanas (+/- 7 dias) durante os primeiros 12 meses, e depois de 12 em 12 semanas (+/- 7 dias)
    3. a segurança (incidência de EAs) será monitorizada continuamente, até 30 dias após a descontinuação
    4. os resultados relatados pelos pacientes serão efectuados de dois em dois ciclos durante os primeiros 12 meses, e depois de três em três ciclos.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    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) No
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA60
    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
    United States
    Portugal
    Spain
    E.8.7Trial has a data monitoring committee No
    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
    Last Subject Last Visit (LSLV)
    Último sujeito Última visita (LSLV)
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    E.8.9.1In the Member State concerned months3
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years6
    E.8.9.2In all countries concerned by the trial months3
    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: 350
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 16
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Patients can give consent through impartial witness and/or legal representative
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state100
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 135
    F.4.2.2In the whole clinical trial 306
    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 as Standard of Care
    Tratamento como padrão de cuidados
    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 Decision2023-01-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-09-16
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA