E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Stage IIIb/c/d or Stage IV no evidence of disease (NED) melanoma following complete resection of the lesion(s) with high risk of relapse. |
Pacientes con melanoma en estadio IIIb/c/d o estadio IV sin pruebas de enfermedad (SPE) después de resección completa de la(s) lesión(es) con alto riesgo de recaída. |
|
E.1.1.1 | Medical condition in easily understood language |
Advanced melanoma. |
Melanoma avanzado. |
|
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 | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053571 |
E.1.2 | Term | Melanoma |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10040891 |
E.1.2 | Term | Skin 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 plus ipilimumab versus ipilimumab alone and nivolumab alone in participants with completely resected stage IIIb/c/d or stage IV no evidence of disease (NED) melanoma. |
Comparar la eficacia, medida por la supervivencia libre de recidiva (SLR) proporcionada por nivolumab más ipilimumab frente a ipilimumab en monoterapia y nivolumab en monoterapia en participantes con melanoma en estadio IIIb/c/d o estadio IV resecado completamente sin pruebas de enfermedad (SPE). |
|
E.2.2 | Secondary objectives of the trial |
_To compare the overall survival provided by nivolumab plus ipilimumab versus ipilimumab alone and/or nivolumab alone in participants with completely resected stage IIIb/c/d or stage IV NED melanoma. _To evaluate the association between PD-L1 expression and RFS. |
- Comparar la supervivencia global proporcionada por nivolumab más ipilimumab frente a ipilimumab en monoterapia y/o nivolumab en monoterapia en participantes con melanoma en estadio IIIb/c/d o estadio IV resecado completamente SPE. - Evaluar la asociación entre la expresión de PD-L1 y la SLR. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
_Completely surgically resected stage IIIb/c/d or stage IV melanoma within 12 weeks of participation in study; _Must have full activity or, if limited, must be able to walk and carry out activities such as light house work or office work; _No prior anti-cancer treatment for melanoma (except surgery for the melanoma lesion(s) and/or except for adjuvant radiation therapy (RT) after neurosurgical resection for central nervous system (CNS) lesions). |
- Melanoma en estadio IIIb/c/d o estadio IV resecado quirúrgicamente de forma completa dentro de las 12 semanas previas a la participación en el estudio; - Debe tener actividad completa o, si es limitada, debe ser capaz de caminar y llevar a cabo actividades como pequeñas tareas domésticas o trabajo de oficina; - Sin tratamiento previo oncológico para el melanoma (excepto cirugía para lesión(es) de melanoma y/o excepto radioterapia (RT) adyuvante después de resección de lesiones del sistema nervioso central (SNC)). |
|
E.4 | Principal exclusion criteria |
_History of uveal melanoma; _Weight less then or equal to 40 kg; _Patients with active, known or suspected autoimmune disease; _Prior treatment with interferon (if complete < 6 months prior to participation in study), anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways. |
- Historia de melanoma de úvea; - Peso menor o igual a 40 kg; - Pacientes con enfermedad autoinmunitaria activa, conocida o de sospecha; - Tratamiento previo con interferon (si se ha completado <6 meses antes de la participación en el estudio), anticuerpos anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 o anti-CTLA-4, o cualquier otro anticuerpo o fármaco que se dirija específicamente a la coestimulación de los linfocitos T o a las vías del punto de control. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Recurrence-free survival (RFS). |
Supervivencia libre de recidiva (SLR). |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Approximately 3 years. |
Aproximadamente 3 años. |
|
E.5.2 | Secondary end point(s) |
_Overall Survival (OS); _PD-L1 expression. |
- Supervivencia global (SG): - Expresión PD-L1. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
_Up to 5 years for OS; _Approximately 3 years for PD-L1 expression. |
- Hasta 5 años para SG; - Aproximadamente 3 años para expresión de PD-L1. |
|
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 | No |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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 | 3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
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 |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
France |
Germany |
Greece |
Hungary |
Israel |
Italy |
New Zealand |
Poland |
Romania |
Russian Federation |
South Africa |
Spain |
Switzerland |
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
|
LVLS |
Última visita del ultimo paciente |
|
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |