- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT02523313
Immunotherapy With Nivolumab or Nivolumab Plus Ipilimumab vs. Double Placebo for Stage IV Melanoma w. NED
10 de diciembre de 2021 actualizado por: Prof. Dr. med. Dirk Schadendorf
A Phase II Randomized, Double-Blind Trial of Immunotherapy With Nivolumab or Nivolumab Plus Ipilimumab Versus Double-Placebo Control as a Post-Surgical/Post-Radiation Treatment for Stage IV Melanoma With No Evidence of Disease
This is a prospective, double-blind placebo-controlled, multicenter, randomized phase II trial testing the adjuvant immunotherapy with Nivolumab plus Ipilimumab Placebo or Nivolumab plus Ipilimumab versus Double Placebo Control as a post-surgical/post-radiation treatment for stage IV melanoma with no evidence of disease (NED).
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Descripción detallada
This study will allow for direct comparison of the clinical benefit provided by Nivolumab monotherapy or Nivolumab combined with Ipilimumab versus double placebo control.
Furthermore, it will also allow for direct comparison of the respective safety profiles of Nivolumab monotherapy or Nivolumab combined with Ipilimumab.
Nivolumab monotherapy was chosen as one of the experimental arms because of a favourable risk-benefit ratio assessed in the large Phase 1 study (MDX1106-03/CA209-003).
The combination of Nivolumab and Ipilimumab was chosen as an experimental arm because of the preliminary evidence from the Phase 1 study CA209-004 suggesting synergy between Nivolumab and Ipilimumab resulting in a higher frequency of patients with increased tumour burden reduction.
Evaluating both Nivolumab monotherapy and the combination of Nivolumab and Ipilimumab will provide clinical data allowing clinicians to select the appropriate treatment for each patient based on their individual risk-benefit ratio.
Tipo de estudio
Intervencionista
Inscripción (Actual)
167
Fase
- Fase 2
Contactos y Ubicaciones
Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.
Ubicaciones de estudio
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Berlin, Alemania, 10117
- Charité Berlin
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Buxtehude, Alemania, 21614
- Elbe Klinikum Buxtehude
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Dresden, Alemania, 01307
- Universitätsklinikum Dresden
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Erfurt, Alemania, 99089
- Helios Klinikum Erfurt
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Essen, Alemania, 45147
- Studienzentrum Hautklinik Universitätsklinikum Essen (AöR) Klinik für Dermatologie
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Gera, Alemania, 07548
- SRH Wald-Klinikum Gera GmbH
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Hannover, Alemania, 30625
- Medizinische Hochschule Hannover
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Heidelberg, Alemania, 69120
- Universitätrsklinikum Heidelberg Dermatologie / NCT
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Heilbronn, Alemania, 74078
- SLK Kliniken Heilbronn GmbH
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Kiel, Alemania, 24105
- Universitäts-Hautklinik Kiel Klinik f. Dermatologie, Venerologie u. Allergologie
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Leipzig, Alemania, 04103
- Universitätsklinikum Leipzig Klinik u. Poliklinik f. Dermatologie, Venerologie u. Allergologie
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Ludwigshafen, Alemania, 67063
- Klinikum der Stadt Ludwigshafen
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Lübeck, Alemania, 23538
- UKSH Campus Lübeck
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Mainz, Alemania, 55131
- Universitätsklinikum Mainz Hautklinik und Polklinik
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Mannheim, Alemania, 68167
- Klinik für Dermatologie, Venerologie und Allergologie UMM - Universitätsmedizin Mannheim
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Minden, Alemania, 32429
- Johannes Wesling Klinikum Minden Hautklinik
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München, Alemania, 80337
- Universitätsklinikum München (LMU)
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Münster, Alemania, 48157
- Fachklinik Hornheide
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Regensburg, Alemania, 93053
- Universitätsklinikum Regensburg
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Tübingen, Alemania, 72076
- Universitätshautklinik Tübingen
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Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
18 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
Inclusion Criteria:
- Stage IV melanoma arising from a primary cutaneous site or metastatic from an unknown primary site with no evidence of disease (NED) after surgery or radiation therapy (conducted within 8 weeks before enrolment)
- Signed written informed consent
- Known BRAF status
- Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
- Minimum life expectancy of five years excluding their melanoma diagnosis
- ECOG performance status of 0 or 1
- Tumor tissue from the resected site of disease must be provided for biomarker analyses. In order to be randomized a subject must have a PD-L 1 expression classification (positive (≥ 5% tumor cells expressing PD-L1) or negative (< 5% tumor cells expressing PD-L1)). If an insufficient amount of tumor tissue from the resected site is provided for analysis, acquisition of additional archived tumor tissue (block and/or slides) for the biomarker analyses is required.
- Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration
- Required laboratory values
- Negative pregnancy test for female subjects and effective contraception (Pearl-Index <1) for both male and female subjects if the risk of conception exists
Exclusion Criteria:
- History of primary uveal or mucosal melanoma
- Prior therapy with CTLA4 or PD1 antibodies
- The patient has psychiatric or addictive disorders that may compromise his/her ability to give informed consent or to comply with the trial procedures.
- Lack of availability for clinical follow-up assessments.
- Any immunosuppressive therapy given within the past 30 days prior to study drug administration (excluding physiologic steroid hormone replacement)
- Other malignancies within the past five years requiring treatment except basal or squamous skin carcinomas or carcinoma in situ of the cervix
- Serious cardiac, gastrointestinal, hepatic or pulmonary disease reducing life expectancy to less than five years
- Patients with serious intercurrent illness, requiring hospitalization.
- Other serious illnesses, e.g., serious infections requiring antibiotics or bleeding disorders.
- The patient is known to be positive for Human Immunodeficiency Virus (HIV) or other chronic infections (HBV, HCV) or has another confirmed or suspected immunosuppressive or immunodeficient condition.
- Known hypersensitivity reaction to any of the components of study treatment
- Pregnancy (absence to be confirmed by ß-HCG urinary test, minimum sensitivity 25IU/L or equivalent units of HCG)) or lactation period
- Women of childbearing potential (WOCBP): Refusal or inability to use effective means of contraception (Pearl-Index <1). WOCBP will be instructed to adhere to contraception until 31 weeks after the last dose of investigational product
- Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year (Pearl-Index <1). Men receiving Nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception until 31 weeks after the last dose of investigational product
- Known alcohol or drug abuse
- Participation in another clinical study and use of any investigational or non-registered product (drug or vaccine) within the 30 days before registration
- Significant disease or condition which, in the investigator's opinion, would exclude the patient from the study
- Legal incapacity or limited legal capacity
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación cruzada
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Comparador activo: Nivolumab + Placebo
Nivolumab (3 mg/kg) i.v.
every 2 weeks + Placebo instead of Ipilimumab on weeks 1, 4, 7 and 10 + Placebo instead of Nivolumab on weeks 4 and 10
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Nivolumab will be applied at a dose of 3 mg/kg given as IV infusion every 2 weeks for up to 1 year after initial dosing or until PD + Placebo instead of Ipilimumab on weeks 1, 4, 7 and 10 + Placebo instead of Nivolumab on weeks 4 and 10.
Otros nombres:
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Experimental: Nivolumab + Ipilimumab
Nivolumab (1 mg/kg) and Ipilimumab (3 mg/kg) i.v.
every 3 weeks for 4 doses.
Both study drugs are administered on the same day over the first 12 weeks + Placebo instead of Nivolumab on weeks 3, 5, 9 and 11.
After week 12: Nivolumab as maintenance and at a dose of 3 mg/kg IV every 2 weeks for up to 1 year after initial dosing (of the combination) or until PD.
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Nivolumab (1 mg/kg) and Ipilimumab (3 mg/kg) will be applied as IV infusion every 3 weeks for 4 doses.
Both study drugs are to be administered on the same day over the first 12 weeks + Nivolumab-Placebo on weeks 3, 5, 9 and 11.
After week 12 Nivolumab is given as maintenance and will be applied at a dose of 3 mg/kg IV every 2 weeks for up to 1 year after initial dosing (of the combination) or until PD.
Otros nombres:
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Comparador de placebos: Double Placebo Control
Placebo instead of Nivolumab and Placebo instead of Ipilimumab i.v.
every 3 weeks for 4 doses.
Both placebos are administered on the same day over the first 12 weeks + Placebo instead of Nivolumab on weeks 3, 5, 9 and 11.
After week 12 Placebo instead of Nivolumab as maintenance and applied as IV every 2 weeks for up to 1 year after initial dosing (of the combination) or until PD.
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Placebo instead of Nivolumab and Placebo instead of Ipilimumab will be applied as IV infusion every 3 weeks for 4 doses.
Both placebos are to be administered on the same day over the first 12 weeks + Placebo instead of Nivolumab on weeks 3, 5, 9 and 11.
After week 12 Placebo instead of Nivolumab is given as maintenance and will be applied intravenously every 2 weeks for up to 1 year after initial dosing (of the combination) or until PD.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
---|---|---|
Efficacy of adjuvant immunotherapy with Nivolumab alone or in combination with Ipilimumab (Recurrence-free survival)
Periodo de tiempo: 24 months after the last patient ended treatment
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Recurrence-free survival (RFS) defined as the time from date of randomization until the date of the first recurrence (local or distant metastasis), new primary melanoma or death from any cause, whichever occurs first.
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24 months after the last patient ended treatment
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Overall survival (OS)
Periodo de tiempo: 24 months after the last patient ended treatment
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The OS of a patient is defined as the time from date of randomization until date of death.
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24 months after the last patient ended treatment
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Time to recurrence (TTR)
Periodo de tiempo: 24 months after the last patient ended treatment
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The TTR of a patient is defined as the time from date of randomization until date of disease recurrence (local or distant metastasis) or melanoma-related death.
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24 months after the last patient ended treatment
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Progression/recurrence free survival 2 (PRFS2) for crossover patients of Arm C
Periodo de tiempo: 24 months after the last patient ended treatment
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The PRFS2 is defined as time from date of randomization until the date of first disease progression per RECIST 1.1 beyond the initial unresectable disease recurrence, the date of second recurrence in patients without evidence of disease after surgery of a resectable first recurrence or the date of death, whichever occurs first.
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24 months after the last patient ended treatment
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Safety / Toxicity All adverse events ≥ Grade 3 according to CTCAE Version 4.0 criteria
Periodo de tiempo: until 90 days after discontinuation of dosing
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All adverse events ≥ Grade 3 according to CTCAE Version 4.0 criteria, that are related to the administration of the investigational agents will be assessed
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until 90 days after discontinuation of dosing
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Dirk Schadendorf, Prof. Dr., Studienzentrum Hautklinik Universitätsklinikum Essen Klinik f. Dermatologie
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Publicaciones Generales
- Livingstone E, Zimmer L, Hassel JC, Fluck M, Eigentler TK, Loquai C, Haferkamp S, Gutzmer R, Meier F, Mohr P, Hauschild A, Schilling B, Menzer C, Kiecker F, Dippel E, Roesch A, Ziemer M, Conrad B, Korner S, Windemuth-Kieselbach C, Schwarz L, Garbe C, Becker JC, Schadendorf D; Dermatologic Cooperative Oncology Group. Adjuvant nivolumab plus ipilimumab or nivolumab alone versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): final results of a randomised, double-blind, phase 2 trial. Lancet. 2022 Oct 1;400(10358):1117-1129. doi: 10.1016/S0140-6736(22)01654-3. Epub 2022 Sep 10.
- Zimmer L, Livingstone E, Hassel JC, Fluck M, Eigentler T, Loquai C, Haferkamp S, Gutzmer R, Meier F, Mohr P, Hauschild A, Schilling B, Menzer C, Kieker F, Dippel E, Rosch A, Simon JC, Conrad B, Korner S, Windemuth-Kieselbach C, Schwarz L, Garbe C, Becker JC, Schadendorf D; Dermatologic Cooperative Oncology Group. Adjuvant nivolumab plus ipilimumab or nivolumab monotherapy versus placebo in patients with resected stage IV melanoma with no evidence of disease (IMMUNED): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet. 2020 May 16;395(10236):1558-1568. doi: 10.1016/S0140-6736(20)30417-7.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio (Actual)
2 de septiembre de 2015
Finalización primaria (Actual)
27 de junio de 2021
Finalización del estudio (Actual)
27 de junio de 2021
Fechas de registro del estudio
Enviado por primera vez
5 de agosto de 2015
Primero enviado que cumplió con los criterios de control de calidad
11 de agosto de 2015
Publicado por primera vez (Estimar)
14 de agosto de 2015
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
13 de diciembre de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
10 de diciembre de 2021
Última verificación
1 de diciembre de 2021
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Neoplasias por tipo histológico
- Neoplasias
- Tumores neuroectodérmicos
- Neoplasias De Células Germinales Y Embrionarias
- Neoplasias De Tejido Nervioso
- Tumores neuroendocrinos
- Nevos y Melanomas
- Melanoma
- Mecanismos moleculares de acción farmacológica
- Agentes antineoplásicos
- Agentes antineoplásicos inmunológicos
- Inhibidores de puntos de control inmunitarios
- Nivolumab
- Ipilimumab
Otros números de identificación del estudio
- IMMUNED
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
NO
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Nivolumab + Placebo
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Universitair Ziekenhuis BrusselAún no reclutando
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Bristol-Myers SquibbReclutamientoMelanomaEspaña, Estados Unidos, Italia, Chile, Grecia, Argentina
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Baptist Health South FloridaBristol-Myers Squibb; NovoCure Ltd.TerminadoGlioblastoma recurrenteEstados Unidos
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HUYABIO International, LLC.Bristol-Myers SquibbReclutamientoMelanoma irresecable o metastásico | Metástasis cerebral progresivaEspaña, Estados Unidos, Italia, Japón, Bélgica, Francia, Nueva Zelanda, Brasil, Corea, república de, Australia, Alemania, Singapur, Chequia, Austria, Sudáfrica, Reino Unido, Puerto Rico
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Brown UniversityBristol-Myers Squibb; The Miriam Hospital; Rhode Island Hospital; Women and Infants...TerminadoCáncer de cuello uterinoEstados Unidos
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Jason J. Luke, MDArray BioPharmaActivo, no reclutandoMelanoma | Carcinoma de células renales | Tumor solido | Cáncer de pulmón de células no pequeñas | Carcinoma de células escamosas de cabeza y cuelloEstados Unidos
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Michael B. Atkins, MDBristol-Myers Squibb; Hoosier Cancer Research NetworkActivo, no reclutandoCarcinoma avanzado de células renalesEstados Unidos
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Bristol-Myers SquibbTerminadoCáncer de pulmónItalia, Estados Unidos, Francia, Federación Rusa, España, Argentina, Bélgica, Brasil, Canadá, Chile, Chequia, Alemania, Grecia, Hungría, México, Países Bajos, Polonia, Rumania, Suiza, Pavo, Reino Unido
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National Health Research Institutes, TaiwanNational Taiwan University Hospital; Mackay Memorial Hospital; China Medical University... y otros colaboradoresReclutamientoCarcinoma hepatocelular (CHC)Taiwán
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Dan ZandbergBristol-Myers SquibbActivo, no reclutandoCarcinoma de células escamosas de cabeza y cuelloEstados Unidos