E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Estrogen Receptor-Positive, HER2-Negative Advanced Breast Cancer |
carcinoma mammario in stadio avanzato positivo ai recettori degli estrogeni (ER) e negativo ai recettori del fattore di crescita dell’epidermide umano 2 (HER2) |
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E.1.1.1 | Medical condition in easily understood language |
Advanced breast cancer |
carcinoma mammario in stadio avanzato |
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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 | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10072737 |
E.1.2 | Term | Advanced 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 demonstrate superiority of AZD9833 plus palbociclib relative to anastrozole plus palbociclib by assessment of PFS |
Dimostrare la superiorità di AZD9833 più palbociclib rispetto ad anastrozolo più palbociclib mediante la valutazione della PFS |
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E.2.2 | Secondary objectives of the trial |
To demonstrate superiority of AZD9833 plus palbociclib relative to anastrozole plus palbociclib by assessment of OS and second progression free survival. To estimate the effectiveness of AZD9833 plus palbociclib relative to anastrozole plus palbociclib by assessment of ORR, DoR, clinical benefit rate at 24 weeks, time to chemotherapy, time to first subsequent therapy or death and time to second subsequent therapy or death. To assess the steady state PK of AZD9833 in combination with palbociclib in all participants who receive at least one dose of AZD9833 per the protocol, for whom there are at least one reportable PK concentration. To assess symptoms, functioning, and health-related quality of life in participants treated with AZD9833 plus palbociclib compared with anastrozole plus palbociclib using the EORTC QLQ-C30 and EORTC QLQBR45 questionnaires. |
Dimostrare la superiorità di AZD9833 più palbociclib rispetto ad anastrozolo più palbociclib mediante la valutazione della OS e della PFS2. Valutare l’efficacia di AZD9833 più palbociclib rispetto ad anastrozolo più palbociclib mediante la valutazione del tasso di risposta obiettiva (ORR), durata della risposta (DoR), del tasso di beneficio clinico a 24 settimane, del tempo alla chemioterapia, del tempo alla prima terapia successiva o al decesso e tempo alla seconda terapia successiva o al decesso. Valutare la PK allo stato stazionario di AZD9833 in combinazione con palbociclib in tutti i partecipanti che ricevono almeno una dose di AZD9833 secondo il protocollo, per i quali vi è almeno una concentrazione PK segnalabile. Valutare sintomi, funzionalità e qualità della vita correlata alla salute nelle/nei partecipanti trattate/i con AZD9833 più palbociclib rispetto ad anastrozolo più palbociclib mediante i questionari EORTC QLQ-C30 ed EORTC QLQ-BR45. |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Other types of substudies Specify title, date and version of each substudy with relative objectives: Qualitative Participant Interviews
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Altre tipologie di sottostudi specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Interviste qualitative ai partecipanti
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E.3 | Principal inclusion criteria |
- Pre-/peri-menopausal women or men can be enrolled if amenable to be treated with concomitant, approved LHRH agonists for the duration of the study treatment. - De novo Stage 4 disease, or recurrence from early stage disease after standard adjuvant endocrine therapy meeting either one of the following criteria: (a) Received at least 24 months of AI treatment as part of their adjuvant therapy without disease progression and disease free interval since the last adjuvant treatment must be greater than 12 months (b) Received at least 24 months of tamoxifen treatment as part of their adjuvant endocrine therapy - Histologically or cytologically documented diagnosis of ER+, HER2-negative breast cancer based on local laboratory results. - Previously untreated with any systemic anti-cancer therapy for their locoregionally recurrent or metastatic ER+ disease. - Measurable disease as defined per RECIST v.1.1 OR at least one lytic or mixed (lytic + sclerotic) bone lesion that can be assessed by CT or MRI. - Eastern Cooperative Oncology Group performance status of 0 or 1. - Adequate organ and marrow function. - Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. |
- Donne o uomini in pre- / peri-menopausa possono essere arruolati se idonei al trattamento con agonisti dell'LHRH concomitanti e approvati per la durata del trattamento in studio - Malattia allo stadio 4 de novo o recidiva dalla malattia allo stadio iniziale dopo la terapia endocrina adiuvante standard che soddisfa uno dei seguenti criteri: (a) Hanno ricevuto almeno 24 mesi di trattamento con AI come parte della loro terapia adiuvante senza progressione della malattia e l’intervallo libero da malattia dall'ultimo trattamento adiuvante deve essere superiore a 12 mesi (b) Hanno ricevuto almeno 24 mesi di trattamento con tamoxifene come parte della loro terapia endocrina adiuvante - Diagnosi istologicamente o citologicamente documentata di carcinoma mammario ER+, HER2- sulla base dei risultati di laboratorio locale. - Non trattati in precedenza con alcuna terapia antitumorale sistemica per loro malattia ER+ locoregionalmente ricorrente o metastatica. - Malattia misurabile come definita secondo RECIST v.1.1 O almeno una lesione ossea litica o mista (litica + sclerotica) che può essere valutata mediante TC o RM - Performance status dell'Eastern Cooperative Oncology Group pari a 0 o 1. - Adeguata funzione degli organi e del midollo. - Disponibilità e capacità di rispettare le visite programmate, il piano di trattamento, i test di laboratorio e altre procedure di studio. |
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E.4 | Principal exclusion criteria |
- Previous neoadjuvant or adjuvant treatment with an AI treatment +/- CDK4/6 inhibitor with disease recurrence while on or within 12 months of completing treatment. - Previous treatment with AZD9833. - Participation in another clinical study with a study treatment or investigational medicinal device administered in the last 4 weeks prior to randomization or concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study. - Advanced, symptomatic, visceral spread, that are at risk of lifethreatening complications in the short term. - Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease. - Any clinically important and symptomatic heart disease. - Currently pregnant (confirmed with positive pregnancy test) or breastfeeding - As judged by the investigator, any evidence of diseases (such as severe or uncontrolled systemic diseases, renal transplant and active bleeding diseases) which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize compliance with the protocol. - Any concurrent anti-cancer treatment. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial. |
- Precedente trattamento neoadiuvante o adiuvante con un trattamento AI +/- inibitore CDK4 / 6 con recidiva della malattia durante o entro 12 mesi dal completamento del trattamento. - Precedente trattamento con AZD9833. - Partecipazione a un altro studio clinico con un trattamento in studio o un dispositivo medicinale sperimentale somministrato nelle ultime 4 settimane prima della randomizzazione o l'arruolamento simultaneo in un altro studio clinico, a meno che non si tratti di uno studio clinico osservazionale (non interventistico) o durante il periodo di follow-up di uno studio interventistico. - Diffusione avanzata, sintomatica, viscerale, a rischio di complicazioni potenzialmente letali a breve termine. - Metastasi del SNC attive note, non controllate o sintomatiche, meningite carcinomatosa o malattia leptomeningea. - Qualsiasi malattia cardiaca clinicamente importante e sintomatica. - Attualmente incinta (confermata con test di gravidanza positivo) o in allattamento. - Come giudicato dallo sperimentatore, qualsiasi evidenza di malattie (come malattie sistemiche gravi o non controllate, trapianto renale e malattie emorragiche attive) che, a parere dello sperimentatore, renda indesiderabile la partecipazione del partecipante allo studio o che comprometterebbe la compliance con il protocollo. - Qualsiasi trattamento antitumorale concomitante Le informazioni sopra riportate non includono tutte gli aspetti rilevanti per la potenziale partecipazione di un paziente a una sperimentazione clinica. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) assessed by the Investigator as defined by response evaluation criteria in solid tumors (RECIST) version 1.1. |
Sopravvivenza libera da progressione (PFS) valutata dallo sperimentatore come definita in base ai criteri di valutazione della risposta nei tumori solidi (RECIST) versione 1.1. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization until progression per RECIST 1.1 as assessed by the investigator at local site or death due to any cause (up to 5 years). |
Dalla randomizzazione fino alla progressione secondo RECIST 1.1 come valutato dallo sperimentatore presso il centro locale o morte per qualsiasi causa (fino a 5 anni). |
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E.5.2 | Secondary end point(s) |
1. Overall survival (OS) 2. Progression-free survival 2 (PFS2) 3. Objective response rate (ORR) assessed by the Investigator as defined by RECIST version 1.1 4. Duration of response (DoR) assessed by the Investigator as defined by RECIST version 1.1 5. Time to second subsequent therapy (TSST) 6. Time to chemotherapy (TTC) 7. Time to first subsequent anti-cancer therapy (TFST) 8. Clinical benefit rate at 24 weeks (CBR24) 9. Plasma concentration of AZD9833 at specified timepoints 10. Change from baseline in EORTC QLQ-C30 and EORTC QLQ-BR45 Scales |
1. sopravvivenza globale (OS) 2. sopravvivenza libera da progressione 2 (PFS2) 3. tasso di risposta obiettiva (ORR), valutato dallo sperimentatore secondo i criteri RECIST 1.1 4. durata della risposta (DoR) valutata dallo sperimentatore secondo i criteri RECIST 1.1 5. tempo alla seconda terapia successiva (TSST) 6. tempo alla chemioterapia (TTC) 7. tempo alla prima terapia anti-tumorale successiva (TFST) 8. tasso di beneficio clinico a 24 settimane (CBR24) 9. concentrazione plasmatica di AZD9833 a specifici punti temporali 10. Cambiamento dal basale nei questionari EORTC QLQ-C30 e EORTC QLQ-BR45 |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. Up to approximately 8 years 2-7. Up to approximately 5 years 8. At Week 24 9. On Day 15 10. Up to approximately 5 years |
1. fino a circa 8 anni 2-7. fino a circa 5 anni 8. alla settimana 24 9. al giorno 15 10. . fino a circa 5 anni |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
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 | No |
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 | 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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 102 |
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 |
Canada |
China |
India |
Japan |
Russian Federation |
Taiwan |
Turkey |
United States |
Austria |
Belgium |
Bulgaria |
Finland |
France |
Germany |
Hungary |
Italy |
Norway |
Poland |
Portugal |
Slovakia |
Switzerland |
United Kingdom |
Czechia |
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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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The end of the study is defined as the date of the last visit/contact of the last participant in the study or last scheduled procedure for the last participant in the study globally. |
La fine dello studio è definita come la data dell'ultima visita / contatto dell'ultimo partecipante allo studio o dell'ultima procedura programmata per l'ultimo partecipante allo studio a livello globale. |
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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 | 8 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 8 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |