E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Breast Neoplasms, Neoplasm Metastasis |
Neoplasia al seno, metastasi neoplastiche |
|
E.1.1.1 | Medical condition in easily understood language |
Breast Cancer |
Carcinoma mammario |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
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 progression-free survival of imlunestrant (Arm A) to the standard comparator of Investigator’s Choice Endocrine Therapy of either fulvestrant or exemestane (Arm B) •To compare the progression-free survival of imlunestrant plus abemaciclib (Arm C) to imlunestrant (Arm A)
|
Paragonare la sopravvivenza libera da progressione della patologia associata a Imlunestrant (Braccio A) rispetto al comparatore standard (braccio B), una terapia endocrina a base di fulvestrant o exemestane a scelta dello sperimentatore
Paragonare la sopravvivenza libera da progressione della patologia associata a Imlunestrant in associazione con Abemaciclib (Braccio C) rispetto a Imlunestrant (Braccio A) |
|
E.2.2 | Secondary objectives of the trial |
•To compare OS of Arm A to Arm B, and Arm C to Arm A •To compare other efficacy objectives of Arm A to Arm B, and Arm C to Arm A •To assess the safety and tolerability of each treatment arm •To evaluate the effectiveness of Arm A compared to Arm B and Arm C compared to Arm A based on PROs of pain using the Worst Pain NRS •To assess the PK of imlunestrant (Arm A and Arm C) •To assess the PK of abemaciclib and its metabolites (Arm C) |
• Paragonare la sopravvivenza globale nel braccio A rispetto al braccio B e nel braccio C rispetto al braccio A • Paragonare altri parametri di efficacia nel braccio A rispetto al braccio B e nel braccio C rispetto al braccio A • Valutare l'efficacia e la sicurezza in ciascun braccio di trattamento • Valutare l'efficacia nel braccio A rispetto al braccio B e nel braccio C rispetto al braccio A basandosi sull'autovalutazione del dolore da parte dei pazienti attraverso una scala di valutazione numerica del dolore massimo • Valutare la farmacocinetica di imlunestrant (Braccio A e C) • Valutare la farmacocinetica di abemaciclib dei suoi metaboliti (Braccio C) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
· Have a diagnosis of ER+, HER2- locally advanced or metastatic breast cancer · Have disease that has demonstrated progression on or after an aromatase inhibitor alone or in combination with a CDK4/6 inhibitor. oPatients are expected to have received prior treatment with a CDK4/6 inhibitor if this treatment is approved and can be reimbursed · Must be deemed appropriate for treatment with endocrine therapy · If female, have a postmenopausal status by natural or surgical means or by ovarian function suppression · Have RECIST evaluable disease (measurable disease and/or nonmeasurable bone-only disease) · Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group scale (Oken et al. 1982) · Have adequate renal, hematologic, and hepatic organ function · Must be able to swallow capsules/tablets
|
• Diagnosi di carcinoma mammario metastatico o localmente avanzato ER+ e HER2- • Progressione della patologia durante o dopo il trattamento con un inibitore dell'aromatasi, da solo o in combinazione con un inibitore di CDK4/6 • Precedente trattamento con un inibitore CDK4/6 se questo trattamento è approvato e può essere rimborsato • Paziente adatto a ricevere una terapia endocrina • Se di sesso femminile, il paziente deve essere in post-menopausa, naturalmente o in seguito ad intervento chirurgico o per soppressione della funzione ovarica • Patologia valutabile secondo i criteri di valutazione della risposta per i tumori solidi "RECIST" (patologia misurabile e/o non misurabile solo nelle ossa) • Performance status uguale a 0 o 1 secondo la scala Eastern Cooperative Oncology Group (Oken et al. 1982) • Adeguata funzionalita' renale, ematologica ed epatica • Paziente in grado di assumere capsule/compresse |
|
E.4 | Principal exclusion criteria |
· Have received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, or any investigational-ER-directed therapy (including SERDs and non-SERDs), any PI3K-, mTOR- or AKT- inhibitor · Have visceral crisis, lymphangitic spread within the lung, or any evidence of leptomeningeal disease. · Have symptomatic or untreated brain metastasis. · Have serious preexisting medical conditions that, in the judgment of the investigator, would preclude participation in this study · Known allergic reaction against any of the components of the study treatment
|
• Precedente trattamento con chemioterappia (ad esclusione di chemioterapia adiuvante/neoadiuvante), fulvestrant o qualsiasi terapia sperimentale diretta sul recettore degli estrogeni (inclusi i degradattori selettivi e non-selettivi del recettore degli estrogeni), inibitori di PIK3, mTOR o AKT • Crisi viscerali, diffusione linfangitica polmonare o evidenza di malattia leptomeningea • Metastasi al cervello sintomatiche o non trattate • Condizione medica preesistente che, secondo lo sperimentatore, preclude la partecipazione allo studio • Allergia nota a uno qualsiasi dei componenti del trattamento sperimentale |
|
E.5 End points |
E.5.1 | Primary end point(s) |
1.Progression Free Survival (PFS) by investigator assessment |
1. Sopravvivenza libera da progressione della malattia valutata dallo sperimentatore |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years) |
1.Tempo che intercorre tra la randomizzazione e la prima documentata progressione della patologia o morte per qualsiasi causa (stimato fino a 3 anni) |
|
E.5.2 | Secondary end point(s) |
2. Overall Survival (OS) 3. Objective Response Rate (ORR): Percentage of Participants Who Achieve a Confirmed Best Overall Response of Complete Response (CR) or Partial Response (PR) 4. Duration of Response (DoR) 5. Clinical Benefit Rate (CBR): Percentage of Participants Who Achieve a Best Overall Response of CR, PR or Stable Disease for greater than or equal to (=) 24 weeks 6. PFS by Estrogen Receptor 1 Gene (ESR1) Mutation Status in Plasma Investigator-assessed PFS by ESR1 mutation status in plasma 7. Progression Free Survival (PFS) by blinded independent review 8. Patient Reported Outcomes (PRO): Time to Worsening of "Worst Pain" Measured by the Worst Pain Numeric Rating Scale (NRS). NRS is a single item, participant-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "pain as bad as you can imagine." 9. Pharmacokinetics (PK): Steady State Plasma Concentrations of Imlunestrant 10.Pharmacokinetics (PK): Steady State Plasma Concentrations of Imlunestrant and Abemaciclib
|
2. Sopravvivenza globale 3. Tasso di risposte obiettive: percentuale di partecipanti che ottengono una confermata risposta completa o parziale 4. Durata della risposta 5. Tasso di beneficio clinico: percentuale di pazienti con risposta completa o risposta parziale o malattia stabile per un periodo = 24 settimane 6. Sopravvivenza libera da progressione (PFS) valutata come stato di mutazione del Recettore degli Estrogeni Gene 1 (ESR1) rilevato nel plasma 7. Sopravvivenza libera da progressione (PFS) valutata con una revisione indipendente condotta in cieco 8. Esiti riferiti dal paziente (PRO): momento in cui si assiste ad un peggioramento del "Dolore Massimo" 9. Farmacocinetica: concentrazione plasmatica di Imlunestrant allo stato stazionario 10. Farmacocinetica: concentrazione plasmatica di Abemaciclib allo stato stazionario |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
2. Randomization until death from any cause (estimated as up to 5 years) 3. Randomization until measured progressive disease (estimated as up to 1 year) 4. Date of CR or PR to date of disease progression or death due to any cause (estimated up to 3 years) 5. Randomization until measured progressive disease (estimated as up to 1 year) 6. Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years) 7. Randomization to the date of first documented progression of disease or death from any cause (estimated as up to 3 years) 8. Screening through follow-up (estimated as up to 3 years) 9. Cycle 2 to Cycle 4 (cycle = 28 days) 10. Cycle 2 to Cycle 4 (cycle = 28 days)
|
2 Tempo tra la randomizzazione e la morte per qualsiasi causa (fino a 5 anni) 3 Tempo tra la randomizzazione e una rilevata progressione (fino a 1 anno) 4 Tempo tra la data della risposta completa o parziale e la data della progressione o della morte per qualsiasi causa (fino a 3 anni) 5 Tempo tra la randomizzazione e una rilevata progressione della patologia (fino a 1 anno) 6 Tempo tra la randomizzazione e la data di prima documentazione della progressione o di morte per qualsiasi causa (fino a 3 anni) 7 Tempo tra la randomizzazione e la data di prima documentazione della progressione o di morte per qualsiasi causa (fino a 3 anni) 8 Dallo screenig al follow-up (fino a 3 anni) 9 Dal ciclo 2 al ciclo 4 (ciclo = 28 giorni) 10 Dal ciclo 2 al ciclo 4 (ciclo = 28 giorni) |
|
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 | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
terapia endocrina scelta dallo sperimentatore |
Investigator’s Choice of Endocrine Therapy |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 63 |
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 |
Australia |
Brazil |
China |
India |
Japan |
Korea, Republic of |
Mexico |
Taiwan |
United States |
Austria |
France |
Netherlands |
Spain |
Czechia |
Germany |
Greece |
Italy |
Belgium |
Russian Federation |
Turkey |
Ukraine |
|
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
|
LVLS in the study or last scheduled procedure for the last participant in the trial globally |
Ultima visita dell'ultimo paziente dello studio a livello globale o ultima procedura programmata per l'ultimo partecipante allo studio a livello globale |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |