E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Node Positive, Early Stage, Hormone Receptor Positive, Human Epidermal Receptor 2 Negative, Breast Cancer |
Tumore della Mammella con Linfonodi Positivi, in Stadio Precoce, Positivo per i Recettori Ormonali, Negativo per il Recettore Epidermico Umano 2 |
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E.1.1.1 | Medical condition in easily understood language |
Breast Cancer |
Tumore della Mammella |
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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 | 10006199 |
E.1.2 | Term | Breast cancer stage I |
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 compare invasive disease free survival (IDFS) for patients receiving adjuvant endocrine therapy plus abemaciclib treatment versus adjuvant endocrine therapy alone in HR+, HER2- breast cancer (Cohort 1 only) |
Confrontare la sopravvivenza libera da malattia invasiva (invasive disease-free survival, IDFS) in pazienti con tumore della mammella HR+, HER2- trattati con abemaciclib pi¿ terapia endocrina adiuvante rispetto a quelli trattati solo con terapia endocrina adiuvante (solo Coorte 1) |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the efficacy, in terms of IDFS, for patients with Ki67 index =20% by central lab - To evaluate the efficacy in terms of distant relapse-free survival (DRFS) and overall survival (OS) - To assess the safety profile - To evaluate the relationship between abemaciclib exposure and clinical (efficacy and safety) outcomes - To evaluate health status, general oncology and breast cancer self-reported health related quality of life |
- Valutare l'efficacia, in termini di IDFS, per pazienti con indice Ki67 =20% (da laboratorio centrale) - Valutare l'efficacia in termini di sopravvivenza libera da recidiva a distanza (distant relapse-free survival, DRFS) e sopravvivenza complessiva (overall survival, OS) - Valutare il profilo di sicurezza - Valutare il rapporto tra l'esposizione ad abemaciclib e gli esiti clinici (efficacia e sicurezza) - Valutare lo stato di salute in termini di qualit¿ della vita correlata alla salute autoriferita per l¿oncologia generale e il tumore della mammella
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Female (regardless of menopausal status) or male =18 years of age •The patient has confirmed HR+, HER2-negative (HER2-), early stage resected invasive breast cancer without evidence of distant metastases. •The patient must have undergone definitive surgical treatment for the current malignancy. •The patient must have tumor tissue from breast (preferred) or lymph node for exploratory biomarker analysis available prior to randomization. •The patient must have high risk of disease recurrence based on nodal status, tumor size, or grade regardless of Ki67 status (Cohort 1), or eligible exclusively based on a Ki67 status (Cohort 2) •The patient must be randomized within within 16 months from the time of surgery •If the patient is currently receiving or initiating standard adjuvant endocrine therapy at time of study entry, she/he must not have received more than 12 weeks following his/her last non-endocrine therapy (surgery, chemotherapy, or radiation) •Women of reproductive potential must have a negative blood pregnancy and agree to use highly effective contraceptive methods •The patient has a ECOG performance status =1
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•Soggetti di sesso femminile (indipendentemente dallo stato menopausale) o maschile, di età =18 anni •Il paziente ha un carcinoma mammario invasivo resecato allo stadio precoce HR+, HER2- (HER2-negativo) confermato, senza evidenze di metastasi a distanza. •Il paziente deve essere stato sottoposto a trattamento chirurgico definitivo per la neoplasia maligna attuale. •Il paziente deve avere a disposizione prima della randomizzazione un tessuto tumorale dalla mammella (preferibilmente) o da linfonodo per l’analisi esploratoria sui biomarcatori. •Il paziente deve presentare un alto rischio di recidiva sulla base dello stato linfonodale, le dimensioni o il grado del tumore indipendentemente dallo stato Ki67 (Coorte 1) o essere eleggibile esclusivamente sulla base di uno stato Ki67 (Cooorte 2) •Il paziente deve essere randomizzato entro 16 settimane dall'intervento •Se sta assumendo o sta iniziando una terapia endocrina adiuvante standard al momento dell’ingresso nello studio, il/la paziente non deve averla assunta più di 12 settimane dall'ultima terapia non endocrina (chirurgia, chemioterapia, radioterapia) •Le donne in età fertile devono sottoporsi a un test di gravidanza da sangue, che deve risultare negativo, e acconsentire a utilizzare metodi contraccettivi ad alta efficacia •Il paziente ha un performance status ECOG =1 |
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E.4 | Principal exclusion criteria |
•The patient has Stage IV (M1), Stage IA, and lymph node-negative breast cancer •Patients with a history of previous breast cancer are excluded, with the exception of LCIS or DCIS treated by locoregional therapy alone =5 years ago. The patient has a history of any other cancer (except non-melanoma skin cancer or carcinoma in situ of the cervix), unless in complete remission with no therapy for a minimum of 5 years. •Females who are pregnant or lactating •The patient has previously received treatment with any CDK4 and CDK6 inhibitor. •The patient is receiving concurrent exogenous reproductive hormone therapy (for example, birth control pills or hormone replacement therapy). •The patient has previously received endocrine therapy for breast cancer prevention (tamoxifen or raloxifene or aromatase inhibitors).
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•Il paziente ha un carcinoma mammario di stadio IV (M1), stadio IA e linfonodo-negativo • Il paziente con un’anamnesi positiva per tumore della mammella sono esclusi, ad eccezione dei LCIS o DCIS trattai con terapia loco-regionale da sola più di 5 anni fa. Paziente che ha un’anamnesi positiva per qualsiasi altro tipo di cancro (a eccezione del tumore cutaneo non melanomatoso e del carcinoma in situ della cervice), salvo in caso di remissione completa senza terapia da almeno 5 anni. •Donne in gravidanza o allattamento •Il paziente ha ricevuto in precedenza un trattamento con un qualsiasi inibitore di CDK4 o CDK6. •Il paziente sta assumendo una terapia ormonale concomitante riproduttiva esogena (ad esempio, pillola contraccettiva o terapia ormonale sostitutiva). •Il paziente ha assunto in precedenza una terapia endocrina per la prevenzione del carcinoma mammario (tamoxifene o raloxifene o inibitori dell’aromatasi). |
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E.5 End points |
E.5.1 | Primary end point(s) |
o compare invasive disease free survival (IDFS) for patients receiving adjuvant endocrine therapy plus abemaciclib treatment versus adjuvant endocrine therapy alone in HR+, HER2- breast cancer (Cohort 1 only). |
Confrontare sopravvivenza libera da malattia invasiva (IDFS) per i pazienti che ricevono la terapia endocrina adiuvante più il trattamento con abemaciclib rispetto alla sola terapia endocrina adiuvante nel carcinoma mammario HR+, HER2- (solo la coorte 1) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After approximately 5 years when approximately 345 events have occured. |
Dopo all’incirca 5 anni, quando si sono verificati circa 345 eventi. |
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E.5.2 | Secondary end point(s) |
Efficacy endpoints: distant relapse-free survival (DRFS), overall survival (OS); Safety endpoints will include but are not limited to the following: TEAEs, SAEs, and hospitalizations Clinical laboratory tests, vital signs, and physical examinations; Steady-state trough abemaciclib concentration (Cmin,ss), hazard ratio for IDFS, DRFS, OS, other efficacy and safety endpoints; Composite and single-item endpoints will be evaluated to examine differentiating effects of abemaciclib across study arms. Measurement will be undertaken using the FACT-B questionnaire for general oncology and breast cancer health-related quality of life; the FACT-ES subscale and additional FACIT-sourced items for cognitive and bladder endocrine therapy symptoms; and the FACIT-F subscale to characterize this symptom know to be associated with oncology, endocrine therapy, and abemaciclib treatment.; The EQ-5D-5L health state profile (the index score and the single-item health status measure) will be used to inform decision modeling for economic evaluations and this questionnaire will be coadministered with and after first completing the FACT/FACIT questionnaire, subscales, and additional items.; Invasive disease-free survival (IDFS) for patients with Ki67 index =20% (both Cohort 1 and Cohort 2 by central lab) |
Endpoint di efficacia: sopravvivenza libera da recidiva a distanza (DRFS), sopravvivenza globale (OS); Gli endpoint di sicurezza includeranno, tra gli altri: TEAE, SAE e ricoveri Test clinici di laboratorio, segni vitali ed esami obiettivi ; Concentrazione minima allo stadio stazionario di abemaciclib (Cmin,ss), hazard ratio per IDFS, DRFS, OS, altri endpoint di efficacia e sicurezza; Saranno valutati endpoint compositi e a elementi singoli per esaminare gli effetti di differenziazione di abemaciclib tra i bracci dello studio. Le misurazioni saranno eseguite utilizzando il questionario FACT-B per oncologia generale e qualit¿ della vita correlata alla salute nel carcinoma mammario; la sottoscala FACT-ES e ulteriori elementi del FACIT per i sintomi cognitivi e della vescica con la terapia endocrina; e la sottoscala FACIT-F per caratterizzare tale sintomo noto per essere associato con oncologia, terapia endocrina e trattamento con abemaciclib.; Il profilo dello stato di salute EQ-5D-5L (il punteggio secondo l¿indice e la misura dello stato di salute per singolo elemento) sar¿ utilizzato fornire informazioni per la modellistica decisionale alla base delle valutazioni economiche e questo questionario sar¿ co-somministrato in concomitanza con e dopo il primo completamento del questionario FACT/FACIT, le sottoscale e gli elementi aggiuntivi.; Sopravvivenza libera da malattia invasiva (IDFS) per pazienti con Ki-67 index =20% (entrambe le coorti 1 e 2 da laboratorio centralizzato) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After approximately 5 years when approximately 345 events have occured. At the end of trial.; After approximately 5 years when approximately 345 events have occured. At the end of trial.; After approximately 5 years when approximately 345 events have occured. At the end of trial.; After approximately 5 years when approximately 345 events have occured. At the end of trial.; After approximately 5 years when approximately 345 events have occured. At the end of trial.; After approximately 5 years when approximately 345 events have occured. At the end of trial. |
Dopo all¿incirca 5 anni, quando si sono verificati circa 345 eventi. Al termine dello studio clinico. ; Dopo all¿incirca 5 anni, quando si sono verificati circa 345 eventi. Al termine dello studio clinico. ; Dopo all¿incirca 5 anni, quando si sono verificati circa 345 eventi. Al termine dello studio clinico. ; Dopo all¿incirca 5 anni, quando si sono verificati circa 345 eventi. Al termine dello studio clinico. ; Dopo all¿incirca 5 anni, quando si sono verificati circa 345 eventi. Al termine dello studio clinico. ; Dopo all¿incirca 5 anni, quando si sono verificati circa 345 eventi. Al termine dello studio clinico.
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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 | 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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | No |
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 | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 181 |
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 |
Chile |
China |
Hong Kong |
India |
Israel |
Japan |
Korea, Republic of |
Mexico |
New Zealand |
Russian Federation |
Saudi Arabia |
South Africa |
Taiwan |
Turkey |
Ukraine |
United States |
Austria |
Belgium |
Denmark |
Finland |
France |
Germany |
Greece |
Hungary |
Italy |
Netherlands |
Poland |
Portugal |
Romania |
Spain |
Sweden |
United Kingdom |
Czechia |
Argentina |
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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 | 10 |
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 | 10 |
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 |