E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
HR+, HER2-, Advanced or Metastatic Breast Cancer |
tumore mammario localmente avanzato o metastatico, HR positivo, HER2 negativo. |
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E.1.1.1 | Medical condition in easily understood language |
Breast Cancer |
Tumore mammario |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10027475 |
E.1.2 | Term | Metastatic breast cancer |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the efficacy of fulvestrant with or without abemaciclib. |
Confrontare l'efficacia di fulvestrant con o senza abemaciclib. |
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E.2.2 | Secondary objectives of the trial |
To further compare the efficacy of fulvestrant with or without abemaciclib To further characterize the safety profile of abemaciclib in combination with fulvestrant To compare PRO measures of fulvestrant with or without abemaciclib To characterize the pharmacokinetics (PK) of abemaciclib in combination with fulvestrant |
Confrontare ulteriormente l'efficacia di fulvestrant con o senza abemaciclib Caratterizzare ulteriormente il profilo di sicurezza di abemaciclib in combinazione con fulvestrant Per confrontare le misure PRO di fulvestrant con o senza abemaciclib Caratterizzare la farmacocinetica (PK) di abemaciclib in combinazione con fulvestrant |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Have a diagnosis of HR+, HER2- breast cancer -Have either advanced disease not amenable to curative surgical treatment or metastatic disease. -Have radiologic evidence of disease progression or recurrence either On treatment with a CDK4 & 6 inhibitor (palbociclib, ribociclib, or abemaciclib) plus AI as initial therapy for advanced disease, or plus ET administered as adjuvant therapy for early-stage breast cancer -Have either measurable disease or non-measurable but evaluable disease. -Have a performance status (PS) of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale (Oken et al. 1982). -Must be deemed appropriate for treatment with ET. -Have discontinued previous treatments and recovered from the acute effects of therapy to at least Grade 1, except for residual alopecia and peripheral neuropathy. -Have adequate organ function. -Males and females may participate. Male participants must agree to use hormone suppression with a gonadotropin-releasing hormone agonist such as goserelin or leuprolide. Female participants must have postmenopausal status due to either surgical/natural menopause or ovarian suppression with a gonadotropin-releasing hormone agonist, such as goserelin or leuprolide. - Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Women of childbearing potential (WOCBP) must test negative for pregnancy prior to initiation of treatment. WOCBP must agree to use 2 forms of effective contraception where at least one form must be highly effective to prevent pregnancy while receiving study treatment, and for 2 years after the last dose of fulvestrant (or according to local approved fulvestrant label). -L'uso della contraccezione dovrebbe essere coerente con le norme locali relative ai metodi di contraccezione per coloro che partecipano a studi clinici. Le donne con potenziale di gravidanza (WOCBP) devono risultare negative alla gravidanza prima dell'inizio del trattamento. WOCBP deve accettare di utilizzare 2 forme di contraccezione efficace in cui almeno una forma deve essere altamente efficace per prevenire la gravidanza durante il trattamento di studio, e per 2 anni dopo l'ultima dose di fulvestrant (o secondo l'etichetta fulvestrant locale approvato). |
-Avere una diagnosi di tumore mammario HR positivo, HER2 negativo -Avere o una malattia avanzata non trattabile chirurgcamente o malattia mtastatica. -Avere evidenza radiologica di progressione della malattia o recidiva o sul trattamento con un inibitore CDK4 & 6 (palbociclib, ribociclib, o abemaciclib) più AI come terapia iniziale per la malattia avanzata, o più ET somministrato come terapia adiuvante per il cancro al seno in fase precoce. -Avere una malattia misurabile o non misurabile, ma valutabile. - Avere uno stato di prestazione (PS) di 0 o 1 su scala Eastern Cooperative Oncology Group (ECOG) (Oken et al. 1982). -Deve essere considerato appropriato per il trattamento con ET. -Aver interrotto i trattamenti precedenti e recuperato dagli effetti acuti della terapia ad almeno Grado 1, fatta eccezione per l'alopecia residua e neuropatia periferica. -Avere una funzione degli organi adeguata -Possono partecipare maschi e femmine. I partecipanti di sesso maschile devono accettare di utilizzare la soppressione degli ormoni con un agonista ormonale che rilascia la gonadotropina, come goserelina o leucprolide. I partecipanti di sesso femminile devono avere uno stato postmenopausale a causa di menopausa chirurgica/naturale o soppressione ovarica con un agonista ormonale che rilascia gonadotropina, come goserelina o leucprolide. - - |
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E.4 | Principal exclusion criteria |
-Have visceral crisis, lymphangitic spread or leptomeningeal carcinomatosis -Have symptomatic or untreated central nervous system (CNS) metastasis. -Have a history within the last 12 months 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. -Have serious preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study - Have a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years -Have a known active systemic infection -Have received any intervening line of systemic therapy between disease recurrence/progression and study screening or more than 1 line of therapy for advanced or metastatic disease.
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-Avere crisi viscerale, diffusione linfangica o carcinomatosi leptomeningeale -Avere metastasi del sistema nervoso centrale sintomatica o non trattata (SNC) -Avere una storia negli ultimi 12 mesi di una delle seguenti condizioni: sincope di eziologia cardiovascolare, aritmia ventricolare di origine patologica (tra cui, ma non limitato a, tachicardia ventricolare e fibrillazione ventricolare), o arresto cardiaco improvviso. -Avere una (o più) patologie gravi preesistenti che, a giudizio del ricercatore, ostacolerebbero la partecipazione a questo studio -Avere una storia di qualsiasi altro cancro (tranne il cancro della pelle nonmelanoma o carcinoma in situ della cervice), a meno che in completa remissione senza terapia per un minimo di 3 anni -Avere un'infezione sistemica attiva nota -Aver ricevuto qualsiasi linea di terapia sistemica tra la malattia recidiva/pogressiva e screening di studio o più di 1 linea di terapia per malattia avanzata o metastatica. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To compare PFS of fulvestrant with or without abemaciclib as determined by investigator assessment using RECIST 1.1 |
Confrontare PFS di fulvestrant con o senza abemaciclib come determinato dalla valutazione del ricercatore utilizzando RECIST 1.1 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
first occurrence of documented disease progression per RECIST 1.1, or death from any cause in the absence of documented progressive disease. |
Prima comparsa della progressione documentata della malattia per RECIST 1.1 o morte per qualsiasi causa in assenza di malattia progressiva documentata. |
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E.5.2 | Secondary end point(s) |
Efficacy endpoints: overall survival (OS), progression-free survival (PFS) by BICR, objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), duration of response (DoR) Safety endpoint: including but not limited to TEAEs, SAEs, deaths and clinical laboratory abnormalities Time to worsening in worst pain via the mBPISF worst pain item Time to deterioration in physical function via the EORTC IL-19 Concentrations of abemaciclib
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Endpoint di efficacia: sopravvivenza globale (OS), sopravvivenza senza progressione (PFS) per BICR, tasso di risposta obiettivo (ORR), tasso di beneficio clinico (CBR), tasso di controllo della malattia (DCR), durata della risposta (Dor) Endpoint di sicurezza: inclusi ma non limitati a TEAEs, SAE, decessi e anomalie cliniche di laboratorio Tempo di peggioramento del dolore peggiore tramite l'elemento mBPISF dolore peggiore Tempo di deterioramento della funzione fisica attraverso l'EORTC IL-19 Concentrazioni di abemaciclib |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
First occurrence of documented disease progression per RECIST 1.1, or death from any cause in the absence of documented progressive disease. At the end of the trial |
Prima comparsa della progressione documentata della malattia per RECIST 1.1 o morte per qualsiasi causa in assenza di malattia progressiva documentata. Alla fine dello studio. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Taiwan |
Australia |
Belgium |
China |
Czechia |
Denmark |
France |
Greece |
Hungary |
Israel |
Italy |
Korea, Republic of |
Mexico |
Poland |
Russian Federation |
Spain |
Sweden |
Turkey |
United States |
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E.8.7 | Trial 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
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 10 |
E.8.9.1 | In the Member State concerned days | 8 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 10 |
E.8.9.2 | In all countries concerned by the trial days | 8 |