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. |
sujetos con melanoma en estadio IIIb/c y IV con resección completa, con alto riesgo de recidiva |
|
E.1.1.1 | Medical condition in easily understood language |
Subjects with completely resected melanoma who are at high risk for recurrence |
Sujetos con melanoma completamente resecado que tienen alto riesgo de recidiva |
|
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 | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053571 |
E.1.2 | Term | Melanoma |
E.1.2 | System Organ Class | 100000004864 |
|
E.1.3 | 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. |
Comparar la eficacia, medida por la supervivencia libre de recidiva (SLR), conseguida con nivolumab frente a ipilimumab en sujetos con melanoma completamente resecado en estadio IIIb/c o estadio IV que tienen alto riesgo de recidiva. |
|
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. |
- Comparar la supervivencia global con nivolumab frente a ipilimumab en sujetos con melanoma en estadio IIIb/c o estadio IV completamente resecado que tienen alto riesgo de recidiva; - Evaluar la seguridad y tolerabilidad globales de nivolumab e ipilimumab en sujetos con melanoma en estadio IIIb/c o estadio IV completamente resecado que tienen alto riesgo de recidiva; - Evaluar si la expresión de PD-L1 es un biomarcador predictivo de SLR; - Evaluar la calidad de vida relacionada con la salud (CdVRS) valorada con el QLQ-C30 de la Organización Europea para la Investigación y el Tratamiento del Cáncer (EORTC). |
|
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 |
- Hombres y mujeres de al menos 15 años de edad (en algunos paises , sólo sujetos con 18 años o mayores pueden reclutarse) -Melanoma completamente resecado por cirugía realizada dentro de las 12 semanas de aleatorización -Estadio IIIb/IIIc o estadío IV antes de la resección completa -Sin tratamiento anti canceroso previo -Funcionamiento adecuado de la circulación sanguinea, hígado y riñón |
|
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 |
- Melanoma ocular o uveal - Historial de meningitis y carcinomatosis - Historial de enfermedad autoinmunitaria - Se excluye a los sujetos con neoplasias malignas previas distintas del melanoma, a menos que se haya alcanzado una remisión completa al menos 3 años antes de la entrada en el estudio -Tratamiento dirigido frente a melanoma resecado que se administra después de la cirugía. -Test positivo de Hepatitis B, Hepatitis C o VIH conocido |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Recurrence-free-survival |
Supervivencia libre de recidiva |
|
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 |
El análisis final del objetivo principal tendrá lugar cuando todos los sujetos tengan un mínimo de 36 meses de seguimiento. |
|
E.5.2 | Secondary end point(s) |
Overall survival |
Supervivencia global |
|
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. |
El análisis final de la supervivencia global tendrá lugar cuando todos los sujetos tengan un mínimo de 48 meses de seguimiento. |
|
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 |
Evaluaciones de de resultados en salud; Evaluaciones de inmunogenicidad |
|
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 | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 4 |
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, 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. |
El estudio terminará una vez que el seguimiento de la supervivencia haya concluido |
|
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 | |
E.8.9.1 | In the Member State concerned days | |
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 |