Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   41449   clinical trials with a EudraCT protocol, of which   6808   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).


    Phase 1 trials conducted solely in adults and that are not part of an agreed PIP are not public in the EU CTR (refer to European Guidance 2008/C 168/02   Art. 3 par. 2 and   Commission Guideline 2012/C 302/03,   Art. 5) .
     
    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:2020-001648-24
    Sponsor's Protocol Code Number:MedOPP321_ABIGAIL
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-06-04
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2020-001648-24
    A.3Full title of the trial
    randomized, 2-arm, open-label, phase II study of abemaciclib combined with
    endocrine therapy (letrozole or fulvestrant) with or without a short course of
    induction chemotherapy with paclitaxel as first-line therapy in patients with
    unresectable locally advanced or metastatic HR-positive/HER2-negative breast
    cancer with aggressive disease criteria. (ABIGAIL)
    Studio randomizzato, a doppio braccio, in aperto, di fase II di abemaciclib combinato con terapia endocrina (letrozolo o fulvestrant), con o senza un breve ciclo di chemioterapia di induzione con paclitaxel come terapia di prima linea, in pazienti con carcinoma mammario HR-positivo/HER2-negativo non resecabile localmente avanzato o metastatico con criteri patologici aggressivi (ABIGAIL)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study of abemaciclib combined with endocrine therapy (letrozole or fulvestrant)
    with or without a short course of chemotherapy with paclitaxel in patients with
    unresectable locally advanced or metastatic breast cancer with aggressive disease criteria.
    Uno studio di abemaciclib combinato con la terapia endocrina (letrozolo o fulvestrante) con o senza un breve ciclo di chemioterapia con paclitaxel in pazienti con tumore al seno non resecabile localmente avanzato o metastatico con criteri di malattia aggressivi.
    A.3.2Name or abbreviated title of the trial where available
    ABemaciclib, ET ± paclItaxel in aGgressive HR+/HER2- MBC trIaL: ABIGAIL
    Studio sperimentale di Abemaciclib, TE ± paclitaxel in MBC aggressivo HR+/HER2: (ABIGAIL)
    A.4.1Sponsor's protocol code numberMedOPP321_ABIGAIL
    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 SponsorMEDICA SCIENTIA INNOVATION RESEARCH S.L.
    B.1.3.4CountrySpain
    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 supportLilly S. A. U.
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMedica Scientia Innovation Research (MedSIR)
    B.5.2Functional name of contact pointCarla Rioja
    B.5.3 Address:
    B.5.3.1Street AddressTorre Glòries. Av. Diagonal, 211, Planta 27
    B.5.3.2Town/ cityBarcellona
    B.5.3.3Post code08018
    B.5.3.4CountrySpain
    B.5.4Telephone number0034932214135
    B.5.5Fax number0034932992382
    B.5.6E-mailcarla.rioja@medsir.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 Paclitaxel Teva
    D.2.1.1.2Name of the Marketing Authorisation holderTeva Italia S.r.l.
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePaclitaxel
    D.3.2Product code [L01C D01]
    D.3.4Pharmaceutical form Concentrate for solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPaclitaxel
    D.3.9.1CAS number 33069-62-4
    D.3.9.2Current sponsor codePaclitaxel
    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 number30
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Paclitaxel Teva
    D.2.1.1.2Name of the Marketing Authorisation holderTeva Italia S.r.l.
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product namePaclitaxel
    D.3.2Product code [Paclitaxel]
    D.3.4Pharmaceutical form Concentrate for solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNPaclitaxel
    D.3.9.1CAS number 33069-62-4
    D.3.9.2Current sponsor codepaclitaxel
    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 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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 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 Verzenios
    D.2.1.1.2Name of the Marketing Authorisation holderEli Lilly Nederland B.V.
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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 nameAbemaciclib
    D.3.2Product code [L01XE50]
    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 INNAbemaciclib
    D.3.9.2Current sponsor codeAbemaciclib
    D.3.9.4EV Substance CodeSUB171907
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Previously untreated unresectable locally advanced or metastatic hormone receptor (HR)-positive/ human epidermal growth factor receptor 2 (HER2)-negative breast cancer with aggressive disease criteria.
    Carcinoma mammario non resecabile localmente avanzato o metastatico con criteri di malattia aggressiva, non trattato precedentemente, positivo al recettore ormonale (HR)/negativo al recettore del fattore di crescita epidermico umano 2 (HER2).
    E.1.1.1Medical condition in easily understood language
    Advanced or metastatic breast cancer.
    carcinoma mammario avanzato o metastatico
    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 10072740
    E.1.2Term Locally advanced breast cancer
    E.1.2System Organ Class 100000004864
    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 the efficacy, as measured by 12-week overall response rate (ORR), of abemaciclib combined with endocrine therapy (ET) (letrozole or fulvestrant) versus paclitaxel in patients with unresectable locally advanced or metastatic
    HR-positive/HER2- negative breast cancer with aggressive disease criteria.
    Comparare l'efficacia, misurata in base al tasso di risposta globale (ORR) a 12 settimane, di abemaciclib combinato con terapia endocrina (ET) (letrozolo o fulvestrant) rispetto a paclitaxel in pazienti con carcinoma mammario HR-positivo/HER2-negativo non resecabile localmente avanzato o metastatico con criteri di malattia aggressiva.
    E.2.2Secondary objectives of the trial
    To compare the efficacy –as measured by ORR, clinical benefit rate (CBR),
    12-week progression-free survival (PFS) rate, PFS, time to response (TTR),
    duration of response (DoR), overall survival (OS), maximum tumor shrinkage
    (MTS), time to first subsequent therapy (TFST), time to second subsequent therapy (TSST), and time to first chemotherapy (TFC) for patients included in Arm A– safety and tolerability, and the patient-reported global quality of life (QoL), functioning, and symptoms of abemaciclib combined with ET (letrozole or fulvestrant) versus paclitaxel. Exploratory objectives • To evaluate predictive and/or prognostic and/or pharmacodynamic biomarkers associated with disease activity status or response to study treatments on archival and/or fresh tumor tissue and blood samples.
    Comparare l'efficacia - misurata sulla base di ORR, tasso di beneficio clinico (CBR), tasso di sopravvivenza libera da progressione a 12 settimane (PFS), PFS, tempo di risposta (TTR), durata della risposta (DoR), sopravvivenza complessiva (OS), massima riduzione del tumore (MTS), tempo alla prima successiva terapia (TFST), tempo alla seconda successiva terapia (TSST), e tempo alla prima chemioterapia (TFC) per pazienti inclusi nel Braccio A – nonché la sicurezza e la tollerabilità, e la qualità della vita complessiva riferita dal paziente (QoL), il funzionamento, e i sintomi di abemaciclib combinato con ET (letrozolo o fulvestrant) rispetto a paclitaxel.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Signed ICF prior participation in any study-related activities
    2.Male/female patients#18y time signed ICF
    3.ECOG performance status of 0/1
    4.Life expectancy at least 24weeks
    5.Pre-menopausal/peri-menopausal women who are being treated w/ a luteinizing hormone-releasing hormone analog for at least 28d prior to study entry(if shorter,post-menopausal levels of serum estradiol/follicle-stimulating hormone [FSH]must be confirmed analytically)/post-menopausal women as defined by any of following criteria:
    a.Documented bilateral oophorectomy
    b.Age#60y
    c.Age<60y & cessation of regular menses for#12m consecutive w/ no alternative pathological/physiological cause;serum estradiol &/or FSH level within laboratory’s reference range for post-menopausal females
    6.Unresectable locally advanced/MBC not amenable to resection w/ curative intent
    7.At least 1of following aggressive disease criteria:
    a.Presence of visceral disease
    b.Either radiological as per RECIST v1.1 /Clinical evidence of progressive disease (PD)on /within 36m of completing adjuvant ET
    c.High histological grade &/or PgR-negative status on primary tumor
    d.LDH >1.5×ULN
    8.Histologically confirmed ERs- &/or PGR(PgR)-positive & HER2-negative breast cancer based on local testing on the most recent analyzed biopsy
    9.Measurable disease as per RECIST v1.1 w/ at least 1site of disease amenable to biopsy.Patients w/ bone lesions as only sites of metastatic disease are not eligible,except for patients w/ identifiable soft tissue components,evaluable by cross sectional imaging techniques such as CT /MRI,and that meet the definition of measurability according RECIST v1.1
    10.Willingness & ability to provide tumor biopsy from metastatic site /primary breast tumor at time of inclusion to perform exploratory studies If not feasible,patient eligibility should be evaluated by Sponsor
    11.Willingness to provide blood samples for exploratory studies at
    baseline,after 2w treatment & at progression (or treatment termination prior to start alternative anti-cancer therapy)
    12.Patients relapsing on a CDK 4/6 inhibitor-based regimen in the neoadjuvant /adjuvant setting will be suitable for the study if disease progression is confirmed after at least 12m following CDK4/6 treatment completion
    13.No prior systemic therapy for unresectable locally advanced /metastatic disease
    14.Radiation therapy for metastatic disease permitted,patient must have fully recovered from the acute effects & at least 14d must have elapsed b/w the last dose & randomization
    15.Resolution of all acute toxic effects of prior anti-cancer therapy to
    Grade#1 as determined by NCI-CTCAE v5.0 (except for Grade#2 neuropathy,alopecia,toxicities not considered a safety risk at investigator's discretion) within at least 14d prior to D1
    16.Adequate hematologic & organ function within 14d before the 1st treatment on D1C1,defined by:
    a.WBC>3.0×109/L;ANC#1.5×109/L(w/t GCSF support within 2w prior D1C1)Platelet count#100×109/L(w/t transfusion within 2w prior D1C1);Hemoglobin>9.0g/dL (w/t transfusion within 2w prior D1C1)
    b.Serum albumin#3g/dL,Total bilirubin#1.5×ULN(#2×ULN in Gilbert’s disease)AST/ALT#3.0×ULN(in liver metastases #5×ULN)ALP#2.5×ULN(in liver and/or bone metastases #5×ULN)
    c.Serum creatinine<1.5×ULN /creatinine clearance #30mL/min based on Cockcroft#Gault eGFR
    d.PTT(or aPTT and INR#1.5×ULN
    17.For women of childbearing potential:agreement to remain abstinent (refrain from heterosexual intercourse) /use highly effective contraceptive methods/ 2effective contraceptive methods,as per protocol.Women of childbearing potential must have a neg serum pregnancy test within 7d before treatment initiation
    18.Male patients should have their partners who are women of childbearing potential use highly effective contraceptive methods/ 2 effective contraceptive methods,as per protocol
    19.Able to swallow oral medication
    20.Patients who are reliable,willing to be available for the duration of study and are willing to follow study procedures
    1.Firmare CI prima della partecipazione allo studio
    2.Pazienti maschi/femmine=18aa al momento della firma
    3.Performance Status ECOG 0/1
    4.Aspettativa di vita=24 sett
    5.Donne pre-menopausa/peri-menopausa in terapia con analogo ormone di rilascio ormone luteinizzante x almeno 28gg prima inizio(se - tempo,livelli di estradiolo sierico/ormone FSH confermati analiticamente)o donne post-menopausa:
    a.Ovariectomia bilaterale documentata
    b.Età=60aa
    c.Età<60aa e cessazione regolari mestruazioni x=12mm consecutivi senza causa patologica o fisiologica alternativa;e livelli sierici estradiolo e/o FSH entro intervallo di riferimento di laboratorio
    6.Carcinoma non resecabile localmente avanzato/MBC non suscettibile di resezione con intento curativo
    7.Almeno 1 criteri malattia aggressiva:
    a.Presenza patologia viscerale
    b.Conferma radiologica x RECIST v1.1 /clinica,PD al momento del/entro 36mm dopo completamento adiuvante ET
    c.Alto grado istologico e/o status PGR- sul tumore primario
    d.LDH>1.5×ULN
    8.Carcinoma confermato istologicamente con test locali sulla +recente biopsia analizzata con ERs e/o PGR(con=1%cellule colorate+ secondo linee guida NCC e ASCO) HER2- (0/1+ x immunoistochimica o 2+ a - x test ISH)
    9.Malattia misurabile x RECIST v 1.1 con almeno 1sito malattia suscettibile biopsia.No pazienti con lesioni ossee come unici siti di malattia metastatica,- pazienti con componenti identificabili tessuti molli,valutabili mediante TC/MRI e conformi misurabilità x RECIST v1.1
    10.Disponibilità e capacità fornire biopsia tumorale da sito metastatico/tumore mammario primario nell'inclusione x studi esplorativi.altrimenti,ammissibilità paziente valutata da personale qualificato
    11.Disponibilità x campioni di sangue x studi esplorativi al basale,dopo 2sett trattamento e progressione(o al termine del trattamento in studio prima di iniziare una terapia antitumorale alternativa)
    12.I pazienti recidivanti in regime basato sull’inibitore CDK4/6 in ambito neoadiuvante o adiuvante saranno ammessi lo studio se la progressione della malattia è confermata dopo almeno 12mm dal completamento del trattamento con CDK4/6
    13.Nessuna precedente terapia sistemica x malattia localmente avanzata o metastatica non resecabile
    14.È consentita radioterapia x malattia metastatica,il paziente deve essersi completamente ripreso dagli effetti acuti e devono essere trascorsi almeno 14gg tra ultima dose e randomizzazione
    15.Risoluzione fino grado=1 almeno 14gg prima del G1 di tutti gli effetti tossici acuti della precedente terapia antitumorale determinata mediante NCI-CTCAE v.5.0(eccez. neuropatia periferica grado=2,alopecia o altre non considerate rischio x il paziente)
    16.Adeguata funzione ematologica e organica nei 14gg precedenti il primo trattamento nel G1C1:
    a.WBC>3.0×109/L;ANC=1,5x109/L(no fattori GCSF 2sett prima del G1C1); Piastrine totali=100x109/L (no trasfusioni 2sett prima del G1C1);Emoglobina>9.0g/dL(no trasfusioni 2sett prima del G1C1)
    b. Albumina sierica=3g/dL;Bilirubina totale=1,5×ULN(=2×ULN patologia Gilbert); AST/ALT=3,0×ULN(=5×ULN in metastasi epatiche);ALP=2,5×ULN(=5×ULN in metastasi epatiche e/o ossee).
    c.Creatinina sierica<1,5×ULN o clearance creatinina=30mL/min in base eGFR Cockcroft-Gault.
    d.PTT(o taPTT e INR=1,5×ULN
    17.x donne in età fertile:accettare astinenza rapporti eterosessuali o utilizzare metodi contraccettivi altamente efficaci, o 2 metodi contraccettivi efficaci come protocollo, durante trattamento e x almeno 3sett dopo ultima dose,e evitare donare ovuli durante stesso periodo. è necessario un test gravidanza sierico neg entro 7gg prima inizio studio
    18.Anche i pazienti di sesso maschile devono far usare alle loro partner in età fertile metodi contraccettivi altamente efficaci,o 2 metodi contraccettivi efficaci come protocollo,durante trattamento e x almeno 3sett dopo ultima dose, astenersi dal donare sperma
    19.Capacità di deglutire farmaci orali
    20. Affidabilità,disponibilità ad impegnarsi x la durata dello studio e a seguire le procedure
    E.4Principal exclusion criteria
    1. Known hypersensitivity to abemaciclib, letrozole, fulvestrant, paclitaxel, and/or any of their excipients.
    2. Are currently receiving an investigational drug in a clinical study or participating in any other type of medical research judged not to be scientifically or medically compatible with this study.
    Note: For patients who stopped receiving an investigational drug in another clinical study, a washout period of 21 days or 5- half-lives (whichever is shorter) must be observed before entering the trial.
    3. Formal contraindication to ET defined as visceral crisis and rapidly or symptomatic progressive visceral disease.
    4. Known concurrent malignancy or malignancy within 5 years of study enrollment except for carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the medical monitor is required.
    5. Known active brain metastases and/or carcinomatous meningitis. Participants with previously treated brain
    metastases may participate provided they are radiologically stable for =4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable, and without requirement of steroid treatment for =14 days prior to first dose of study treatment.
    6. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
    7. Major surgical procedure within 14 days prior to treatment initiation or anticipation of the need for a major surgical procedure during the course of the study other than for diagnosis.
    Note: Placement of central venous access catheter(s) (e.g., port or similar) is not considered a major surgical procedure and is therefore permitted.
    8. Active bleeding diathesis, previous history of bleeding diathesis, or chronic anti-coagulation treatment (the use of low molecular weight heparin is allowed if used prophylactically).
    9. Serious and/or uncontrolled pre-existing medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g., estimated creatinine clearance <30 ml/min], history of major surgical resection involving the stomach or small bowel, or pre-existing Crohn’s disease or ulcerative colitis or a pre-existing chronic condition resulting in baseline Grade 2 or higher diarrhea).
    10. Current known infection with HIV, hepatitis B virus (HBV), or hepatitis C virus (HCV). Patients with past HBV infection or resolved HBV infection (defined as having a negative hepatitis B surface antibody [HBsAg] test and a positive hepatitis B core antibody [HBcAb] test, accompanied by a negative HBV DNA test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
    11. Active bacterial or fungal infection at the time of enrolment (requiring antibiotics or antifungal agents at time of initiating study treatment).
    12. History of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
    13. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through at least 3 weeks after the last dose of study treatment.
    1. Ipersensibilità nota ad abemaciclib, letrozolo, fulvestrant, paclitaxel e/o ad uno qualsiasi dei loro eccipienti.
    2. Se attualmente assume un farmaco sperimentale in uno studio clinico o partecipa a qualsiasi altro tipo di ricerca medica giudicata non scientificamente o clinicamente compatibile con questo studio.
    Nota: Per pazienti che abbiano terminato l’assunzione di un farmaco sperimentale in un altro studio clinico, deve essere osservato un periodo di washout di 21 giorni o 5 emivite (a seconda di quale sia più breve) prima di iniziare lo studio.
    3. Controindicazione convenzionale alla ET, definita come crisi viscerale e patologia viscerale rapidamente o sintomaticamente progressiva.
    4. Neoplasie concomitanti o neoplasie insorte entro 5 anni prima dell'arruolamento allo studio, ad eccezione di carcinoma in situ della cervice, carcinoma cutaneo non-melanoma o cancro uterino allo stadio I. Per altri tumori considerati a basso rischio di recidiva è necessario discutere con l’osservatore medico.
    5. Note metastasi cerebrali attive e/o meningite carcinomatosa. I partecipanti con metastasi cerebrali precedentemente trattate possono partecipare a condizione che siano radiologicamente stabili per =4 settimane come da imaging ripetuto (si noti che l'imaging ripetuto deve essere eseguito durante lo screening dello studio), clinicamente stabili e non necessitino trattamento steroideo nei =14 giorni precedenti la prima dose di trattamento dello studio.
    6. Noti disturbi psichiatrici o abuso di sostanze che potrebbero interferire con la cooperazione con i requisiti della sperimentazione.
    7. Interventi chirurgici importanti nei 14 giorni precedenti l'inizio del trattamento o previsione della necessità di un intervento chirurgico importante non diagnostico durante il corso dello studio.
    Nota: Il posizionamento di cateteri di accesso venoso centrale (ad esempio, port o simili) non è considerato una procedura chirurgica importante ed è pertanto consentito.
    8. Diatesi emorragica attiva, precedente anamnesi di diatesi emorragica o trattamento anticoagulante cronico (l'uso di eparina a basso peso molecolare è consentito se usato come profilassi).
    9. Patologie preesistenti gravi e/o incontrollate che, a giudizio dello sperimentatore, precludano la partecipazione a questo studio (per esempio, malattia polmonare interstiziale, dispnea a riposo grave o che richieda ossigenoterapia, insufficienza renale grave [ad esempio, stima della clearance della creatinina <30 ml/min], anamnesi di resezioni chirurgiche importanti allo stomaco o al piccolo intestino, o preesistente malattia di Crohn o colite ulcerosa, o una condizione cronica preesistente che dia luogo a diarrea di grado 2 o superiore al basale).
    10. Presenza di infezione da HIV, virus dell'epatite B (HBV) o virus dell'epatite C (HCV). Sono ammessi i pazienti con passata infezione da HBV o infezione da HBV risolta (definita come negatività al test dell'anticorpo di superficie per l'epatite B [HBsAg] e positività al test per l'anticorpo centrale per l'epatite B [HBcAb], accompagnato da negatività al test per L'HBV DNA). I pazienti positivi per l'anticorpo HCV sono ammessi solo se la reazione a catena della polimerasi (PCR) è negativa per L'HCV RNA.
    11. Infezione batterica o micotica attiva al momento dell'arruolamento (se necessita di antibiotici o agenti antimicotici al momento dell'inizio del trattamento in studio).
    12. Anamnesi di una qualsiasi delle seguenti condizioni: sincope di eziologia cardiovascolare, aritmia ventricolare di origine patologica (inclusi, a titolo esemplificativo, tachicardia ventricolare e fibrillazione ventricolare), o arresto cardiaco improvviso.
    13. Gravidanza o allattamento, o aspettativa di concepire o generare figli entro la durata prevista dello studio, a partire dalla visita di screening fino a 3 settimane dopo l'ultima dose del trattamento in studio.
    E.5 End points
    E.5.1Primary end point(s)
    12-week ORR, defined as complete response (CR) or partial response (PR), during the first 12 weeks of treatment as per blinded independent central review, using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1.
    ORR a 12 settimane, definito come risposta completa (CR) o risposta parziale (PR), durante le prime 12 settimane di trattamento, come da revisione centrale indipendente in cieco, utilizzando i criteri di valutazione della risposta nei tumori solidi (RECIST) versione (v) 1.1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    12 weeks
    12 settimane
    E.5.2Secondary end point(s)
    • ORR, defined as the best overall response of CR or PR, as per investigator assessment and per blinded independent central review, using RECIST v 1.1;
    • CBR, defined as an objective response (CR or PR), or stable disease for at least 24 weeks, as per investigator assessment and blinded independent central review using RECIST v 1.1;
    • 12-week PFS rate, defined as the proportion of patients with disease progression or death from any cause, whichever occurs first during the first 12 weeks from randomization, as per investigator assessment and blinded independent central review using RECIST v 1.1;
    • PFS, defined as the period of time from randomization to the first occurrence of disease progression or death from any cause, whichever occurs first, as per investigator assessment and blinded independent central review using RECIST v 1.1;
    • TTR, defined as the time from randomization to time of the first objective tumor response (tumor shrinkage of =30%) observed in patients who achieved a CR or PR, as per investigator assessment and blinded independent central review using RECIST v 1.1;
    • DoR, defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first, as per investigator assessment and per blinded independent central review using RECIST v 1.1;
    • OS, defined as the time from randomization to death from any cause, as per investigator assessment and blinded independent central review using RECIST v 1.1;
    • MTS from baseline in the size of target tumor lesions, defined as the biggest decrease, or smallest increase if no decrease will be observed, as per investigator assessment and blinded independent central review using RECIST v 1.1;
    • TFST, defined as the time from randomization to the time a patient starts his/her first-line treatment (first subsequent therapy);
    • TSST, defined as the time from randomization to the time a patient starts his/her second-line treatment (second subsequent therapy);
    • TFC, defined as the time from randomization to the time a patient included in Arm A starts his/her first-line chemotherapy;
    • Incidence of adverse events (AEs) as assessed by the investigator, with severity determined through the use of USA National Cancer Institute’s Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v 5.0); Overall change from baseline in patient-reported global QoL, general health status, functioning and symptoms; time to deterioration in global QoL; and time to deterioration in pain.
    • ORR, definita come la migliore risposta complessiva di CR o PR, secondo la valutazione dello sperimentatore e come da revisione centrale indipendente in cieco, utilizzando RECIST v 1.1;
    • CBR, definita come risposta oggettiva (CR o PR), o malattia stabile per almeno 24 settimane, secondo la valutazione dello sperimentatore e come da revisione centrale indipendente in cieco utilizzando RECIST v 1.1;
    • Tasso di PFS a 12 settimane, definito come percentuale di pazienti con progressione della malattia o morte per qualsiasi causa, a seconda di quale si verifichi prima, durante le prime 12 settimane dalla randomizzazione, secondo la valutazione dello sperimentatore e come da revisione centrale indipendente in cieco utilizzando RECIST v 1.1;
    • PFS, definito come il periodo di tempo dalla randomizzazione alla prima comparsa di progressione della malattia o morte per qualsiasi causa, a seconda di quale si verifichi prima, secondo la valutazione dello sperimentatore e come da revisione centrale indipendente in cieco utilizzando RECIST v 1.1;
    • TTR, definito come il periodo di tempo dalla randomizzazione alla prima risposta oggettiva del tumore (riduzione della massa del tumore=30%) osservato in pazienti che hanno esitato una CR o PR, secondo la valutazione dello sperimentatore e come da revisione centrale indipendente in cieco utilizzando RECIST v 1.1;
    • DoR, definito come il periodo di tempo dalla prima insorgenza di una risposta oggettiva documentata fino alla progressione della malattia o morte per qualsiasi causa, a seconda di quale si verifichi prima, determinata localmente dallo sperimentatore e come da revisione centrale indipendente in cieco utilizzando RECIST 1,1;
    • OS, definito come il periodo di tempo dalla randomizzazione alla morte per qualsiasi causa, secondo la valutazione dello sperimentatore e come da revisione centrale indipendente in cieco utilizzando RECIST v 1.1;
    • MTS dal basale nella dimensione delle lesioni tumorali mirate, definita come maggiore riduzione, o minore incremento qualora non si osservi alcuna riduzione, secondo la valutazione dello sperimentatore e come da revisione centrale indipendente in cieco utilizzando RECIST v 1.1;
    • TFST, definito come il periodo di tempo dalla randomizzazione all’inizio del trattamento di prima linea del paziente (prima terapia successiva);
    • TSST, definito come il periodo di tempo dalla randomizzazione all’inizio del trattamento di seconda linea del paziente (seconda terapia successiva);
    • TFC, definito come il periodo di tempo dalla randomizzazione all’inizio della chemioterapia di prima linea per un paziente incluso nel Braccio A;
    • Incidenza di eventi avversi (AE) valutata dallo sperimentatore, con gravità determinata in base ai criteri terminologici comuni per gli eventi avversi del National Cancer Institute USA versione 5.0 (NCI-CTCAE v 5.0);
    • Variazione complessiva rispetto al basale di QoL, stato di salute generale, efficacia e sintomi riferiti dal paziente; periodo di tempo al peggioramento di Qol complessiva; e periodo di tempo al peggioramento del dolore.
    E.5.2.1Timepoint(s) of evaluation of this end point
    12 weeks
    12 settimane
    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) 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 Yes
    E.8.1.6Cross over Yes
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA32
    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 Information not present in EudraCT
    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
    The end of study is defined as the last patient's last visit at the end of the follow-up period. The EoS will occur at 18 months after last patient is randomized, unless study is terminated prematurely.
    La fine dello studio è definita come l'ultima visita dell'ultimo paziente al termine del periodo di follow-up. La fine dello studio avverrà 18 mesi dopo che l'ultimo paziente è stato randomizzato, a meno che lo studio non si concluda prematuramente
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months9
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months9
    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: 160
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 160
    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 state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 160
    F.4.2.2In the whole clinical trial 160
    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)
    none
    nessuno
    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 Decision2021-06-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-03-24
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, visit the EMA Service Desk , log in using your EMA account and open a ticket specifying "EU CTR" in your request.
    If you do not have an account, please visit the EMA Account management page page click on "Create an EMA account" and follow the instructions.
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2022 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA