| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Estrogen receptor (ER)-positive, HER2-negative locally advanced or metastatic breast cancer |
| Tumore mammario positivo per il recettore degli estrogeni e HER2 negativo, localmente avanzato o metastatico |
|
| E.1.1.1 | Medical condition in easily understood language |
| Breast cancer begins when abnormal cancerous cells in the breast grow and multiply to create a tumor. This tumor can be ER-positive, HER2-negative |
| Il cancro al seno inizia quando le cellule cancerose anormali nel seno crescono e si moltiplicano per creare un tumore. Questo tumore può essere ER-positivo, HER2-negativo |
|
| 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 | 23.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10070575 |
| E.1.2 | Term | Estrogen receptor positive breast cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 23.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10070577 |
| E.1.2 | Term | Oestrogen receptor positive breast cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
|
| 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 evaluate the efficacy of GDC-9545 combined with palbociclib compared with letrozole combined with palbociclib on the basis of progression-free survival |
| -Valutare l’efficacia di GDC-9545 in associazione a palbociclib rispetto a letrozolo in associazione a palbociclib sulla base della sopravvivenza libera da progressione |
|
| E.2.2 | Secondary objectives of the trial |
-To evaluate the efficacy of GDC-9545 combined with palbociclib compared with letrozole combined with palbociclib on the basis of overall survival, objective response rate, duration of response, clinical benefit rate, time to deterioration, time to deterioration in pain presence and interference, time to deterioration in physical functioning, time to deterioration in role functioning, time to deterioration in global health status
-To evaluate the safety of GDC-9545 combined with palbociclib compared with letrozole combined with palbociclib
-To characterize the GDC-9545 pharmacokinetics profile when given in combination with palbociclib
-To characterize the palbociclib pharmacokinetics profile when given in combination with GDC-9545 or in combination with letrozole
|
-Valutare l’efficacia di GDC-9545 in associazione a palbociclib rispetto a letrozolo in associazione a palbociclib sulla base della sopravvivenza globale, tasso di risposta obiettiva, durata della risposta, Tasso di beneficio clinico, tempo al peggioramento, tempo al peggioramento della presenza e dell’interferenza del dolore, tempo al peggioramento dell’attività fisica, tempo al peggioramento del funzionamento nel ruolo, tempo al peggioramento delle condizioni generali di salute
-Valutare la sicurezza di GDC-9545 in associazione a palbociclib rispetto a letrozolo in associazione a palbociclib
-Caratterizzare il profilo PK di GDC-9545 somministrato in associazione a palbociclib
-Caratterizzare il profilo PK di palbociclib somministrato in associazione a GDC 9545 o in associazione a letrozolo |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
–Age >= 18 years at time of signing Informed Consent Form
–For women who are premenopausal or perimenopausal or men: treatment with approved LHRH agonist therapy for the duration of study treatment
–Locally advanced (recurrent or progressed) or metastatic adenocarcinoma of the breast, not amenable to treatment with curative intent
–Documented ER-positive tumor and HER2-negative tumor, assessed locally
–No history of systemic anti-cancer therapy for locally advanced (recurrent or progressed) or metastatic disease
–Measurable disease as defined per RECIST v.1.1
–Eastern Cooperative Oncology Group Performance Status 0-1
–Adequate organ function |
- Età >=18 anni al momento della sottoscrizione del modulo di consenso informato
- Per le donne in stato postmenopausale o premenopausale o uomini: trattamento con una terapia a base di agonista dell’LHRH approvata per l’intera durata del trattamento in studio
- Adenocarcinoma mammario localmente avanzato (recidivante o andato incontro a progressione) o metastatico non candidabile a trattamento con intento curativo
- Tumore ER-positivo documentato e tumore HER2-negativo valutato localmente
- Nessuna terapia antitumorale sistemica pregressa per malattia localmente avanzata (recidivante o andata incontro a progressione) o metastatica.
- Malattia misurabile secondo i criteri RECIST v.1.1.
- Performance status secondo l’Eastern Cooperative Oncology Group pari a 0-1.
- Adeguata funzionalità d’organo |
|
| E.4 | Principal exclusion criteria |
–Disease recurrence during or within 12 months of completing prior neoadjuvant or adjuvant treatment with an AI
–Disease recurrence during or within 12 months of completing prior neoadjuvant or adjuvant treatment with any CDK4/6 inhibitor
–Prior treatment with a SERD
–Prior treatment with tamoxifen is permitted, provided the patient did not experience disease recurrence within the first 24 months of treatment with tamoxifen
–Treatment with any investigational therapy within 28 days prior to study treatment
–Advanced, symptomatic, visceral spread that is at risk of life-threatening complications
–Known active uncontrolled or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
–Active cardiac disease or history of cardiac dysfunction
–Pregnant or breastfeeding |
-Recidiva della malattia durante o entro 12 mesi dal completamento del precedente trattamento neoadiuvante o adiuvante con un inibitore dell’aromatasi
- Recidiva della malattia durante o entro 12 mesi dal completamento del precedente trattamento neoadiuvante o adiuvante con qualsiasi inibitore delle chinasi ciclina-dipendente 4/6
- Precedente trattamento con un degradatore selettivo dei recettori degli estrogeni
- È ammesso il precedente trattamento con tamoxifene, a condizione che il paziente non abbia manifestato recidiva della malattia entro i primi 24 mesi del trattamento con tamoxifene
- Trattamento con qualsiasi terapia sperimentale nei 28 giorni precedenti il trattamento in studio
- Diffusione viscerale sintomatica avanzata a rischio di complicanze potenzialmente letali
- Metastasi attive note non controllate o sintomatiche a carico del sistema nervoso centrale
- Malattia cardiaca attiva o anamnesi positiva per disfunzione cardiaca
- Gravidanza o allattamento |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 1. Progression-free survival as determined by the investigator |
| 1. Sopravvivenza libera da progressione determinata dallo sperimentatore |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| 1. Approximately 82 months |
| 1. Circa 82 mesi |
|
| E.5.2 | Secondary end point(s) |
Efficacy
1. Overall survival
2. Objective response rate as determined by the investigator
3. Duration of response as determined by the investigator
4. Clinical benefit rate as determined by the investigator
5. Time to deterioration in pain level
6. Time to deterioration in pain presence and interference, in physical functioning, in role functioning, and in global health status
7. Incidence and severity of adverse events, with severity determined according to NCI CTCAE v5.0
8. Change from baseline in targeted vital signs
9. Plasma concentration of GDC-9545 at specified timepoints
10. Plasma concentration of palbociclib at specified timepoints |
Efficacia
1. Sopravvivenza globale
2. Tasso di risposta obiettiva secondo quanto stabilito dallo sperimentatore
3. Durata della risposta secondo quanto stabilito dallo sperimentatore
4. Tasso di beneficio clinic secondo quanto stabilito dallo sperimentatore
5. Tempo al peggioramento del livello di dolore
6. Tempo al peggioramento della presenza e dell’interferenza del dolore dell’attività fisica, del funzionamento nel ruolo e delle condizioni generali di salute
7. Incidenza e severità degli eventi avversi, con severità stabilita in base ai criteri comuni di terminologia per gli eventi avversi del National Cancer Institute (NCI), versione 5.0 (CTCAE v5.0)
8. Variazione dei parametri vitali di interesse rispetto al basale
9. Concentrazione plasmatica di GDC-9545 a specifici timepoint
10. Concentrazione plasmatica di palbociclib a specifici timepoint |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-7. Approximately 82 months
8. From baseline (Day-28 to -1) to 82 months
9. Day 1 and 15 of Cycle 1, Day 1 of Cycle 2, 4, 8, and 16 and at treatment discontinuation
10. Day 1 and 15 of Cycle 1 |
1-7. Circa 82 mesi
8. Dal basale (giorno -28 al -1) a 82 mesi
9. Giorno 1 e 15 del ciclo 1, giorno 1 del ciclo 2, 4, 8, e 16 e ad interruzione del trattamento
10. Giorno 1 e 15 del ciclo 1 |
|
| 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 | No |
| 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 | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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 | 12 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 118 |
| 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 |
| Australia |
| Brazil |
| Canada |
| China |
| Hong Kong |
| Korea, Republic of |
| Mexico |
| New Zealand |
| Peru |
| South Africa |
| Turkey |
| Ukraine |
| United States |
| Belgium |
| Denmark |
| France |
| Germany |
| Hungary |
| Italy |
| Poland |
| Portugal |
| Spain |
| Switzerland |
| United Kingdom |
| Argentina |
| Greece |
|
| 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
|
| The end of this study (global phase and China extension phase) is defined as the date when the last patient, last visit occurs or the date at which the last data point required for statistical analysis or overall survival follow-up is received from the last patient, whichever occurs later. The end of the study is expected to occur at least 60 months after the last patient is enrolled. In addition, the Sponsor may decide to terminate the study at any time. |
| La fine dello studio (fase globale e fase di estensione cinese) coinciderà con la data in cui si terrà l’ultima visita dell’ultimo paziente o con la data di ricezione dell’ultima osservazione relativa all’ultimo paziente necessaria per l’analisi statistica o il follow up per la sopravvivenza globale. Lo studio dovrebbe terminare almeno 60 mesi dopo l’arruolamento dell’ultimo paziente. Il promotore potrà inoltre decidere di interrompere lo studio in qualsiasi momento. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 0 |
| E.8.9.1 | In the Member State concerned months | 82 |
| E.8.9.1 | In the Member State concerned days | 0 |
| E.8.9.2 | In all countries concerned by the trial years | 0 |
| E.8.9.2 | In all countries concerned by the trial months | 82 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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