E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Breast cancer |
Carcinoma mammario |
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E.1.1.1 | Medical condition in easily understood language |
Breast cancer |
Carcinoma 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 | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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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 determine whether amcenestrant once a day (QD) improves the invasive breast cancer-free survival (IBCFS) when compared to tamoxifen QD in patients with early breast cancer as adjuvant treatment |
Determinare se amcenestrant assunto una volta al giorno (QD) migliora la sopravvivenza libera da carcinoma mammario invasivo (IBCFS) rispetto a tamoxifene QD utilizzato come trattamento adiuvante in pazienti con carcinoma mammario allo stadio iniziale |
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E.2.2 | Secondary objectives of the trial |
-To determine whether amcenestrant once a day (QD) improves the invasive disease-free survival (IDFS) when compared to tamoxifen QD in patients with early breast cancer as adjuvant treatment -To evaluate the distant recurrence-free survival (DRFS) in both treatment arms -To evaluate the locoregional recurrences-free survival (LRRFS) in both treatment arms -To evaluate the overall survival (OS) in both treatment arms -To evaluate the breast cancer-specific survival (BCSS) in both treatment arms -To evaluate patient-reported overall treatment-related side effect bother, treatment-related symptoms, and quality of life in both treatment arms -To evaluate safety in both treatment arms -To characterize the pharmacokinetics (PK) of amcenestrant |
- Determinare se amcenestrant assunto una volta al giorno (QD) migliora la sopravvivenza libera da malattia invasiva (IDFS) rispetto a tamoxifene QD utilizzato come trattamento adiuvante in pazienti con carcinoma mammario allo stadio iniziale. - Valutare la sopravvivenza libera da recidiva a distanza (DRFS) in entrambi i bracci di trattamento - Valutare la sopravvivenza libera da recidive locoregionali (LRRFS) in entrambi i bracci di trattamento - Valutare la sopravvivenza globale (OS) in entrambi i bracci di trattamento - Valutare la sopravvivenza specifica per il carcinoma mammario (BCSS) in entrambi i bracci di trattamento - Valutare in entrambi i bracci di trattamento il fastidio complessivo degli effetti collaterali correlati al trattamento, i sintomi correlati al trattamento e la qualità della vita, riportati dal/dalla paziente - Valutare la sicurezza in entrambi i bracci di trattamento - Caratterizzare la farmacocinetica (PK) di amcenestrant |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Adult participants with histologically confirmed diagnosis of adenocarcinoma of the breast with documentation of hormone receptor positive status, irrespective of human epidermal growth factor 2 (HER2) status NOTE: Participants with HER2-positive breast cancer are eligible only if they have completed their adjuvant anti-HER2 treatment and chemotherapy. -With Stage IIB or Stage III, early invasive breast cancer at diagnosis who have undergone breast surgery for the current malignancy. -Who have received prior aromatase inhibitors (AIs) (letrozole, anastrozole or exemestane or any sequence thereof) for at least 6 months and discontinued within 30 months from the initiation of the first AI administration due to AI treatment-related toxicity -Absence of advanced/metastatic disease -Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1 -Capable of giving signed informed consent |
- Partecipanti adulti con diagnosi istologicamente confermata di adenocarcinoma mammario con documentazione dello status del recettore ormonale positivo, indipendentemente dallo status di HER2 NOTA: Partecipanti con carcinoma mammario HER2-positivo sono eleggibili solo se hanno completato il trattamento adiuvante anti-HER2 e la chemioterapia - Partecipanti allo stadio IIB o III, carcinoma mammario invasivo precoce alla diagnosi che sono stati sottoposti a intervento chirurgico al seno per l’attuale tumore maligno. - Partecipanti che hanno ricevuto precedenti inibitori delle aromatasi (AI) (letrozolo, anastrozolo o exemestane o qualsiasi loro sequenza) per almeno 6 mesi e che hanno interrotto l’assunzione entro 30 mesi dall’inizio della prima somministrazione di AI a causa della tossicità correlata al trattamento -Assenza di malattia avanzata/metastatica - Stato di funzionalità 0-1 secondo l’Eastern Cooperative Oncology Group (ECOG) - In grado di fornire il consenso informato firmato |
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E.4 | Principal exclusion criteria |
-Medical history or ongoing gastrointestinal disorders potentially affecting the absorption of amcenestrant and/or tamoxifen. Participants unable to swallow normally and to take tablet and capsules. Predictable poor compliance to oral treatment. Active inflammatory bowel disease or chronic diarrhea, active hepatitis A/B/C, hepatic cirrhosis, short bowel syndrome, or any upper gastrointestinal surgery including gastric resection or banding procedures -Prior breast cancer for which they received an AI -Any other solid tumor or lymphoma diagnosis is not allowed except if the participant has been free from disease for >/=5 years -Pregnant or nursing women, or women of child-bearing potential without a negative pregnancy test prior to randomization -Participants with unrecovered acute toxic effects of prior AI therapy or surgical procedures -Uncontrolled intercurrent illness, including psychiatric conditions that would limit compliance with study requirements -Treatment with any another SERD, tamoxifen or toremifene are not allowed as prior adjuvant therapy but could have been used as neoadjuvant therapy for a total duration of 3 months. Participants who were treated with a SERD, tamoxifen or toremifene in the neoadjuvant setting and who experienced disease progression are not allowed - Participant is receiving concurrent HER2 directed therapy. Appropriate wash out between the last dose of HER2 directed therapy and randomization should be at least 4 weeks |
- Storia medica o disturbi gastrointestinali in corso che potenzialmente influenzano l‘assorbimento di amcenestrant e/o tamoxifene. Partecipanti incapaci di deglutire normalmente e di assumere capsule o compresse. Prevedibile scarsa aderenza al trattamento orale. Malattia infiammatoria intestinale attiva o diarrea cronica, epatite A/B/C attiva, cirrosi epatica, sindrome dell’intestino corto o qualsiasi intervento chirurgico del tratto gastrointestinale superiore, comprese resezione gastrica o procedure di bendaggio. - Precedente carcinoma mammario per il quale si è ricevuto un AI - Qualsiasi altra diagnosi di tumore solido o linfoma non è consentita, tranne nel caso in cui il/la partecipante sia libero/a da malattia da >/= 5 anni - Donne in gravidanza o in allattamento, o donne in età fertile senza un test di gravidanza negativo prima della randomizzazione - Partecipanti con effetti tossici acuti non risolti dalla precedente terapia con AI o da procedure chirurgiche - Malattia intercorrente non controllata, incluse condizioni psichiatriche che limiterebbero l’aderenza ai requisiti dello studio - Non è consentito come precedente terapia adiuvante il trattamento con qualsiasi altro SERD, tamoxifene o toremifene ma potrebbe essere stato usato come terapia neoadiuvante per una durata totale di 3 mesi. I/Le partecipanti che sono stati/e trattati/e con un SERD, tamoxifene o toremifene nel contesto neoadiuvante e che hanno manifestato progressione di malattia non sono ammessi/e - Il/La partecipante sta ricevendo una terapia concomitante diretta contro HER2. Il periodo di sospensione appropriato tra l’ultima dose della terapia mirata a HER2 e la randomizzazione deve essere di almeno 4 settimane |
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E.5 End points |
E.5.1 | Primary end point(s) |
Invasive breast cancer-free survival (IBCFS) |
Sopravvivenza libera da carcinoma mammario invasivo (IBCFS) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization up to approximately 10 years |
Dalla randomizzazione fino a circa 10 anni |
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E.5.2 | Secondary end point(s) |
1) Invasive disease-free survival (IDFS) 2) Distant recurrence-free survival (DRFS) 3) Locoregional recurrences-free survival (LRRFS) 4) Overall survival (OS) 5) Breast cancer-specific survival (BCSS) 6) Patient-reported overall treatment-related side effect bother as measured by the Functional Assessment of Cancer Therapy Item GP-5 (FACT-GP5) 7) Patient-reported treatment-related symptoms as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Breast cancer module (EORTC QLQ-B23) systemic therapy side effects scale 8) Patient-reported quality of life as measured by the EORTC Core Quality of Life Questionnaire (EORTC QLQ-C30) global health status/quality of life (GHQ) scale 9) Number of participants with treatment emergent adverse events (TEAEs) and serious adverse events (SAEs) 10) PK parameter: Plasma concentration of Amcenestrant |
1) Sopravvivenza libera da malattia invasiva (IDFS) 2) Sopravvivenza libera da ricorrenza lontana (DRFS) 3) Sopravvivenza libera da ricorrenza locoregionale (LRRFS) 4) Sopravvivenza globale (OS) 5) Sopravvivenza specifica per il carcinoma mammario (BCSS) 6) Disturbo globale riportato dal paziente correlato al trattamento come misurato dal Functional Assessment of Cancer Therapy Item GP-5 (FACT-GP5) 7) Sintomi riportati dal paziente correlati al trattamento come riportato dall’ European Organisation for Research and Treatment of Cancer (EORTC). Questionario sulla qualità della vita, modulo specifico per il carcinoma mammario (EORTC QLQ-B23) 8) Qualità della vita riportata dal paziente come misurato dal EORTC Core Quality of Life, modulo specifico per stato di salute globale/qualità della vita (GHQ) 9) Numero di partecipanti con eventi avversi emergenti dal trattamento (TEAEs) e eventi avversi seri (SAEs) 10) Parametri farmacocinetici: concentrazione plasmatica di amcenestrant |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1/2/3/4/5)From randomization up to approximately 10 years 6)From baseline up to 2 years after the end of treatment (up to approximately 7 years) 7)From baseline up to 2 years after the end of treatment (up to approximately 7 years) 8)From baseline up to 2 years after the end of treatment (up to approximately 7 years) 9)Up to 30 days after the end of treatment, approximately 5 years 10)Pre-administration day 1 of cycles 2, 7, 13 and 25 (each cycle is 28 days) |
1/2/3/4/5) Dalla randomizzazione fino a circa 10 anni 6) dal basale fino a 2 anni dopo la fine del trattamento (fino a circa 7 anni) 7) dal basale fino a 2 anni dopo la fine del trattamento (fino a circa 7 anni) 8) dal basale fino a 2 anni dopo la fine del trattamento (fino a circa 7 anni) 9) fino a 30 giorni dopo la fine del trattamento, approssimativamente 5 anni 10) giorno 1 di pre-somministrazione dei cicli 2,7,13 e 25 (ogni ciclo dura 28 giorni) |
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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 | 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 | 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 | 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 | 26 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 140 |
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 |
Canada |
Chile |
China |
Georgia |
India |
Japan |
Korea, Republic of |
Mexico |
New Zealand |
Russian Federation |
Taiwan |
Turkey |
Ukraine |
United States |
Austria |
Belgium |
Denmark |
Estonia |
France |
Germany |
Greece |
Hungary |
Ireland |
Italy |
Portugal |
Sweden |
United Kingdom |
Spain |
Switzerland |
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E.8.7 | Trial 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
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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 | 11 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 12 |
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 |