E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
High risk, completely resected Stage IIIb/c and IV melanoma subjects |
Soggetti con melanoma di stadio IIIb/c o stadio IV completamente resecato e ad alto richio di ricomparsa di malattia |
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E.1.1.1 | Medical condition in easily understood language |
Subjects with completely resected melanoma who are at high risk for recurrence
|
Soggetti con melanoma complatamente resecato e ad alto richio di ricomparsa di malattia |
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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 | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053571 |
E.1.2 | Term | Melanoma |
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 compare the efficacy, as measured by recurrence free survival (RFS), provided by nivolumab versus ipilimumab in subjects with completely resected Stage IIIb/c or Stage IV NED melanoma who are at high-risk for recurrence |
Paragonare l’efficacia, misurata come la sopravvivenza libera da recidiva (RFS), a seguito del trattamento con nivolumab verso ipilimumab in soggetti con melanoma di stadio IIIb/c o stadio IV NED completamente resecato e che sono ad alto rischio di recidiva di malattia |
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E.2.2 | Secondary objectives of the trial |
To compare the overall survival of nivolumab vs ipilimumab in subjects with completely resected Stage IIIb/c or Stage IV NED melanoma who are at high risk for recurrence; - To assess the overall safety and tolerability of nivolumab and ipilimumab in subjects with completely resected Stage IIIb/c or Stage IV NED melanoma who are at high risk for recurrence; - To evaluate whether PD-L1 expression is a predictive biomarker for RFS; - To evaluate the Health Related Quality of Life (HRQoL) as assessed by European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 |
Paragonare la sovravviveza complessiva (OS) di nivolumab verso ipilimumab in soggetti con melanoma di stadio IIIb/c o stadio IV NED completamente resecato e che sono ad alto rischio di recidiva di malattia; Valutare la sicurezza e tollerabilità complessiva di nivolumab verso ipilimumab in soggetti con melanoma di stadio IIIb/c o stadio IV NED completamente resecato e che sono ad alto rischio di recidiva di malattia; Valutare se l’espressione di PD-L1 è un biomarker predittivo per la RFS; Valutare la qualità di vita rispetto allo stato di salute (Health Related Quality of Life - HRQoL) in base all’ European Organisation for Research and Treatment of Care (EORTC) QLQ-C30 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Man and woman, 15 years or older (in some countries, only subjects aged 18 years or older will be recruited) -Completely removed melanoma by surgery performed within 12 weeks of randomization -Stage IIIb/C or Stage IV before complete resection - No previous anti-cancer treatment -Adequate function of the blood, kidney, and liver |
- Donne e uomini, dai 15 anni di età in poi (in alcuni paesi verranno arruolati solo soggetti maggiorenni) - Melanoma completamente rimosso chirurgicamente entro 12 settimane dalla randomizzazione -Stadio IIIb/c or Stadio IV prima della resezione completa -Nessun precedente trattamento contro il cancro - Adeguata funzionalità del sangue, rene e fegato |
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E.4 | Principal exclusion criteria |
Ocular or uveal melanoma -History of carcinomatosis meningitis -History of auto-immune disease -Previous non-melanoma cancers unless complete remission since 3 years -Treatment directed against the resected melanoma that is administrated after the surgery -Postive testing for hepatitis B, hepatitis C, or known HIV |
Storia di melanoma oculare o uveale •Storia di meningite carcinomatosa •Storia di malattia autoimmune •Soggetti con una pregressa storia di tumore (non- melanoma) a meno che non ci sia stata remissione di malatia da almeno 3 anni •Trattamento diretto contro il melanoma resecato amministrato dopo la chirurgia •Test positivo a HBV, HCV o HIV noto |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Recurrence-free-survival |
La sopravvivenza libera da recidiva (RFS) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The final analysis of the primary endpoint will take place when all subjects have a minimum of 36 months of follow-up |
L’analisi finale dell’endpoit primario sarà effettuata quando tutti i soggetti avranno raggiunto un minimo di 36 mesi di follow-up |
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E.5.2 | Secondary end point(s) |
Overall survival |
La sopravvivenza complessiva (OS)
|
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The final analysis of overall survival will take place when all subjects have a minimum follow-up of 48 months |
L’analisi finale della sopravvivenza complessiva sarà effettuata quando tutti i soggetti avranno raggiunto un minimo di 48 mesi di follow-up |
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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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Outcomes Research Assessments; Immunogenicity Assessments |
Valutazioni di Outcomes Research; Valutazioni di immunogenicità Immunogenicity Assessments |
|
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) | 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 | 8 |
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 | No |
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 |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
Finland |
France |
Greece |
Hungary |
Ireland |
Italy |
Japan |
Korea, Democratic People's Republic of |
Mexico |
Netherlands |
Norway |
Poland |
Romania |
South Africa |
Spain |
Sweden |
Switzerland |
Taiwan |
Turkey |
United Kingdom |
United States |
|
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 study will end once survival follow-up has concluded |
Lo studio terminerà nel momento in cui il follow-up sulla sopravvivenza sarà concluso |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |