E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with features associated with high-risk of recurrent CSCC disease, who have completed surgery and post-operative RT radiation therapy |
Pazienti con caratteristiche associate a un alto rischio di CSCC ricorrente che hanno completato un intervento chirurgico e una radioterapia (RT) post operatoria |
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E.1.1.1 | Medical condition in easily understood language |
Patients who have high-risk of recurrent CSCC after surgery and radiation therapy. |
Pazienti che hanno un alto rischio di CSCC ricorrente dopo intervento chirurgico e radioterapia. |
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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 | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10041823 |
E.1.2 | Term | Squamous cell carcinoma |
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 |
The primary objective of the study is to compare disease-free survival (DFS) of patients with high-risk cutaneous squamous cell carcinoma (CSCC) treated with adjuvant cemiplimab, versus those treated with (CSCC) treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and radiation therapy (RT) |
L’obiettivo primario dello studio è confrontare la sopravvivenza libera da malattia (DFS) dei pazienti con carcinoma cutaneo a cellule squamose (CSCC) ad alto rischio, trattati con cemiplimab adiuvante, rispetto a quelli trattati con placebo, dopo intervento chirurgico e radioterapia (RT) |
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E.2.2 | Secondary objectives of the trial |
-To compare the overall survival (OS) of high-risk CSCC patients treated with adjuvant cemiplimab, versus those treated with placebo, after surgery and RT - To compare the effect of adjuvant cemiplimab with that of placebo on patients' freedom from locoregional recurrence (FFLRR) after surgery and RT - To compare the effect of adjuvant cemiplimab with that of placebo on patients' freedom from distant recurrence (FFDR) after surgery and RT - To compare the effect of adjuvant cemiplimab with that of placebo on the cumulative incidence of second primary CSCC tumors (SPTs) after surgery and RT - To evaluate the safety of adjuvant cemiplimab and that of placebo in high-risk CSCC patients after surgery and RT |
- Confrontare la sopravvivenza totale (OS) di pazienti con CSCC ad alto rischio trattati con cemiplimab adiuvante, rispetto a quelli trattati con placebo, dopo intervento chirurgico e RT - Confrontare l’effetto di cemiplimab adiuvante con quello del placebo sulla libertà da ricorrenza loco-regionale (FFLRR) nei pazienti dopo intervento chirurgico e RT - Confrontare l’effetto di cemiplimab adiuvante con quello del placebo sulla libertà da ricorrenza a distanza (FFDR) nei pazienti dopo intervento chirurgico e RT - Confrontare l’effetto di cemiplimab adiuvante con quello del placebo sull’incidenza cumulativa di secondi tumori CSCC primari (SPT) dopo intervento chirurgico e RT - Valutare la sicurezza di cemiplimab adiuvante e quella del placebo in pazienti con CSCC ad alto rischio dopo intervento chirurgico e RT |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Men and women =18 years old - For Japan only, men and women =21 years old - Patient with resection of pathologically confirmed CSCC (primary CSCC lesion only, or primary CSCC with nodal involvement, or CSCC nodal metastasis with known primary CSCC lesion previously treated within the draining lymph node echelon), with macroscopic gross resection of all disease - High risk CSCC, as defined in the protocol - Completion of curative intent post-operative radiation therapy (RT) within 2 to 6 weeks of randomization - Eastern Cooperative Oncology Group performance status (ECOG PS) =1 - Adequate hepatic, renal, and bone marrow function as defined in the protocol |
- Uomini e donne con età =18 anni - Solo per il Giappone, uomini e donne con età =21 anni - Pazienti con resezione di CSCC confermato con referto istologico (solo lesione CSCC primaria, o CSCC primario con coinvolgimento nodale, o metastasi nodale di CSCC con lesione primaria nota di CSCC precedentemente trattata entro la matrice del linfonodo drenante), con resezione macroscopica evidente di tutta la malattia - CSCC ad alto rischio, come definito nel protocollo - Completamento di radioterapia (RT) post-operatoria con intento curativo entro 2-6 settimane dalla randomizzazione - Performance Status dell’Eastern Cooperative Oncology Group (ECOG) =1 - Adeguata funzione epatica, renale e del midollo osseo come definita nel protocollo |
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E.4 | Principal exclusion criteria |
- Squamous cell carcinomas (SCCs) arising in non-cutaneous sites as defined in the protocol - Concurrent malignancy other than localized CSCC and/or history of malignancy other than localized CSCC within 3 years of date of randomization as defined in the protocol - Patients with hematologic malignancies - Patients with hematologic malignancies (eg, chronic lymphocytic leukemia (CLL)) - Patients with history of distantly metastatic CSCC (visceral or distant nodal), unless the disease-free interval is at least 3 years (regional nodal involvement of disease in draining lymph node basin that was nodal involvement of disease in draining lymph node basin that was resected and radiated prior to enrollment will not be exclusionary - Ongoing or recent (within 5 years of randomization date) evidence of immunosuppressive treatments, which may suggest risk for immune related adverse events (irAEs). The following are not exclusionary: vitiligo, childhood asthma that has resolved, type 1 diabetes, residual hypothyroidism that required only hormone replacement, or psoriasis that does not require systemic treatment. - Has had prior systemic anti-cancer immunotherapy for CSCC |
- Carcinomi a cellule squamose (SCC) che si presentano in siti non cutanei come definito nel protocollo - Neoplasia maligna concomitante diversa da CSCC localizzato e/o anamnesi di neoplasia maligna diversa da CSCC localizzato entro 3 anni dalla data di randomizzazione come definita nel protocollo. - Pazienti con altre neoplasie maligne ematologiche ( ad es. leucemia linfatica cronica (LLC)) - Pazienti con storia clinica di CSCC metastatico distante (viscerale o nodale distante), salvo che l’intervallo libero da malattia sia almeno 3 anni (il coinvolgimento nodale regionale di malattia nel bacino del linfonodo drenante che sia stato resecato e irradiato prima dell’arruolamento, non sarà motivo di esclusione) - Evidenza in corso o recente (entro 5 anni dalla randomizzazione) di malattia autoimmune significativa che richiede trattamento con terapie immunosoppressive sistemiche, che potrebbe porre il rischio di eventi avversi immuno-correlati (irAE). I seguenti non sono motivi di esclusione: vitiligine, asma infantile che si è risolta, diabete di tipo 1, ipotiroidismo residuo che richiede solo la terapia sostitutiva ormonale, o psoriasi che non richiede trattamento sistemico. -Ha assunto una precedente immunoterapia sistemica antitumorale per CSCC |
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E.5 End points |
E.5.1 | Primary end point(s) |
DFS defined as time from randomization to the first documented disease recurrence (local, regional and/or distant); or death due to any cause. |
La DFS sarà definita come il tempo trascorso dalla randomizzazione alla prima ricorrenza documentata di malattia (locale, regionale e/o distante) o al decesso dovuto a qualsiasi causa |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to 54 months |
Fino a 54 mesi |
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E.5.2 | Secondary end point(s) |
-Overall survival (OS), defined as time from randomization to the date of death. A patient who has not died will be censored on the last known date as alive -FFLRR defined as time from randomization to the date of first locoregional recurrence (LRR). Patients who died without a preceding LRR will be censored on the date of death -Freedom from distant recurrence (FFDR), defined as time from randomization to the date of first distant recurrence (DR). Patients who died without a preceding DR will be censored on the date of death -Cumulative occurrence of second primary cutaneous squamous cell carcinoma tumor (SPTs) for each patient from randomization to occurrence of first primary endpoint event or end of study. -Safety, as measured by the incidence and severity of treatment emergent adverse events (TEAE), deaths, and laboratory abnormalities. |
-La OS verrà definita come il tempo compreso tra la data della randomizzazione e la data del decesso. Un/a paziente che non è deceduto/a sarà censito/a all'ultima data nota in cui era vivo/a -La FFLRR verrà definita come il tempo compreso tra la data della randomizzazione e la data della prima ricorrenza loco-regionale (LRR). I pazienti che sono deceduti senza un precedente LRR saranno censiti alla data del decesso -La libertà da ricorrenza a distanza (FFLDR) verrà definita come il tempo compreso tra la data della randomizzazione e la data della prima ricorrenza a distanza (DR). I pazienti che sono deceduti senza un precedente DR saranno censiti alla data del decesso -Evento cumulativo di secondi carcinomi primari cutanei a cellule squamose (SPT) per ciascun paziente dalla randomizzazione al verificarsi del primo evento di endpoint primario o alla fine dello studio. -Sicurezza, misurata dall’incidenza e dalla gravità degli eventi avversi emergenti dal trattamento (TEAE), decesso e anomalie di laboratorio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to 78 months for OS and Safety Up to 54 months for FFLRR, FFDR, Cumulative occurrence of SPT |
Fino a 78 mesi per OS e Sicurezza Fino a 54 mesi per FFLRR, FFDR, evento cumulativo di SPT |
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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 | Yes |
E.8.1.7.1 | Other trial design description |
Studio in 2 parti, parte 2 opzionale (in aperto) |
2 Part Study. Part 2 optional (unblinded) |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 60 |
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 |
Korea, Republic of |
Mexico |
New Zealand |
Russian Federation |
United States |
Belgium |
France |
Germany |
Greece |
Ireland |
Italy |
Poland |
Spain |
United Kingdom |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 1 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 1 |