- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT02212730
A Study Evaluating the Effect of Pembrolizumab (MK-3475) in Participants With Renal Cell Cancer (MK-3475-031)
22 de junio de 2020 actualizado por: Merck Sharp & Dohme LLC
A Clinical Trial to Evaluate the Effect of Neoadjuvant MK-3475 (Pembrolizumab) Therapy on Intratumoral Immune Infiltrates in Renal Cell Cancer (RCC) Patients Undergoing Surgical Resection
This study will examine the effect of treatment with the neoadjuvant antibody pembrolizumab (MK-3475) on tumors of participants with renal cell cancer (RCC).
The primary hypotheses are that pembrolizumab is well tolerated in participants undergoing RCC tumor resection; and that pembrolizumab will stimulate a 2-fold or greater increase in intratumoral lymphocytic infiltration in at least 30% of participants with RCC.
Descripción general del estudio
Estado
Terminado
Condiciones
Intervención / Tratamiento
Tipo de estudio
Intervencionista
Inscripción (Actual)
10
Fase
- Fase 1
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:
- Have a newly diagnosed RCC, with a primary tumor diameter of more than 4 cm (>= T1b), not previously treated, and be a candidate for operative tumor resection
- Be willing and able to undergo pre-treatment baseline image-guided core biopsy of their primary RCC
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale
- Demonstrate adequate organ function
- Female is not breast feeding, is postmenopausal or surgically sterile; demonstrates non-pregnant state, and agrees to use two acceptable methods of birth control throughout the trial, until 120 days after the last dose of treatment
- Male with female partner of childbearing potential agrees to use adequate method of contraception throughout study, until 120 days after last dose of treatment or last blood draw.
Exclusion Criteria:
- Is currently participating in, or has participated in a study with an investigational agent or device within 4 weeks prior to first dose of study therapy
- Has a diagnosis of immunosuppression or has received systemic steroid therapy, or any other form of immunosuppressive therapy within 4 weeks prior to first dose of study therapy
- Has had prior chemotherapy, targeted small molecule, or radiation therapy for treatment of RCC
- Has a known additional (other than RCC) malignancy that is progressing or requires active treatment
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
- Has an active, or documented history of autoimmune disease, with the exceptions of vitiligo or resolved childhood asthma/atopy
- Has a history of (non-infectious) pneumonitis that required treatment with steroids or current pneumonitis.
- Has an active infection requiring systematic therapy
- Is receiving anticoagulant therapy, with the exception of low dosage aspirin
- Has severe cardiovascular disease or symptomatic ischemic heart disease
- Has hepatic decompensation
- Has uncontrolled thyroid dysfunction
- Has uncontrolled diabetes mellitus
- Has known psychiatric or substance abuse disorders
- Female is pregnant or breastfeeding
- Is expecting to conceive children within the projected maximum duration of the trial, extending through 120 days after the last dose of treatment or the last blood draw
- Has received prior therapy with any antibody or drug (including ipilimumab) specifically targeting T-cell co-stimulation or checkpoint pathway
- Has a known history of human immunodeficiency virus (HIV)
- Has known active hepatitis B or C
- Has received a live vaccine within 30 days prior to screening
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 paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Neoadjuvant Pembrolizumab + RCC Resection
Participants received pembrolizumab, 200 mg intravenously (IV) once every 3-week cycle for up to 2 cycles followed by standard of care (SOC) renal cell carcinoma (RCC) surgical resection; and then received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles).
Post-resection pembrolizumab was only administered to participants who enrolled after Protocol Amendment 04.
|
200 mg administered by IV, once every 3-week cycle for a maximum of 2 cycles
Otros nombres:
Standard of care surgical resection of RCC tumor
200 mg administered by IV, once every 3-week cycle for a maximum of 17 cycles
Otros nombres:
|
|
Experimental: RCC Resection
Participants received SOC renal cell carcinoma (RCC) surgical resection; and then may have received post-resection pembrolizumab 200 mg IV once every 3 week cycle for up to approximately 1 year (17 cycles).
Post-resection pembrolizumab was only administered to participants who enrolled under Protocol Amendment 04.
|
Standard of care surgical resection of RCC tumor
200 mg administered by IV, once every 3-week cycle for a maximum of 17 cycles
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Number of Participants With an Adverse Event (AE) During the Neoadjuvant Pembrolizumab Regimen
Periodo de tiempo: Up to Week 16
|
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment.
The number of participants who experienced an AE during their regimen of neoadjuvant pembrolizumab was presented.
|
Up to Week 16
|
|
Number of Participants Who Discontinued Treatment Due to an Adverse Event
Periodo de tiempo: Up to 56 weeks
|
An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment.
The number of participants who discontinued study drug due to an adverse event is presented.
|
Up to 56 weeks
|
|
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD3+ Lymphocytic Infiltration
Periodo de tiempo: Baseline and Week 7
|
The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD3+ lymphocytic infiltration is presented.
Evaluations were based on pathologist score.
|
Baseline and Week 7
|
|
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral CD8+ Lymphocytic Infiltration
Periodo de tiempo: Baseline and Week 7
|
The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral CD8+ lymphocytic infiltration is presented.
Evaluations were based on pathologist score.
|
Baseline and Week 7
|
|
Number of Participants Treated With Neoadjuvant Pembrolizumab With a 2-fold or Greater Change From Baseline in Intratumoral FoxP3+ Lymphocytic Infiltration
Periodo de tiempo: Baseline and Week 7
|
The number of participants who received neoadjuvant pembrolizumab and showed a 2-fold or greater change from baseline in intratumoral FoxP3+ (forkhead box protein P3 positive) lymphocytic infiltration is presented.
Evaluations were based on pathologist score.
|
Baseline and Week 7
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Change From Baseline in Levels of Gene Expression of Immune Modulatory Receptors in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
Periodo de tiempo: Baseline and Week 7
|
The change from baseline in levels of gene expression of immune modulatory receptors in tumors of participants treated with neoadjuvant pembrolizumab was presented.
|
Baseline and Week 7
|
|
Change From Baseline in Number of T Cells in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
Periodo de tiempo: Baseline and Week 7
|
The change from baseline in number of T cells in tumors of participants treated with neoadjuvant pembrolizumab was presented.
|
Baseline and Week 7
|
|
Change From Baseline in Number of Activated T Cells in Peripheral Blood of Participants Treated With Neoadjuvant Pembrolizumab
Periodo de tiempo: Baseline and Week 7
|
The change from baseline in the number of activated T cells in peripheral blood of participants treated with neoadjuvant pembrolizumab was presented.
|
Baseline and Week 7
|
|
Change From Baseline in Levels of Programmed Cell Death 1 Ligand 1 (PD-L1) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
Periodo de tiempo: Baseline and Week 7
|
The change from baseline in levels of programmed cell death 1 ligand 1 (PD-L1) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.
|
Baseline and Week 7
|
|
Change From Baseline in Levels of Programmed Cell Death 1 Ligand 2 (PD-L2) Protein in Tumors of Participants Treated With Neoadjuvant Pembrolizumab
Periodo de tiempo: Baseline and Week 7
|
The change from baseline in levels of programmed cell death 1 ligand 2 (PD-L2) protein in tumors of participants treated with neoadjuvant pembrolizumab in participants who received neoadjuvant pembrolizumab was presented.
|
Baseline and Week 7
|
Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
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)
3 de diciembre de 2014
Finalización primaria (Actual)
5 de julio de 2019
Finalización del estudio (Actual)
5 de julio de 2019
Fechas de registro del estudio
Enviado por primera vez
6 de agosto de 2014
Primero enviado que cumplió con los criterios de control de calidad
6 de agosto de 2014
Publicado por primera vez (Estimar)
8 de agosto de 2014
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
16 de julio de 2020
Última actualización enviada que cumplió con los criterios de control de calidad
22 de junio de 2020
Última verificación
1 de junio de 2020
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Neoplasias por tipo histológico
- Neoplasias
- Neoplasias Urológicas
- Neoplasias urogenitales
- Neoplasias por sitio
- Enfermedades Renales
- Enfermedades urológicas
- Adenocarcinoma
- Carcinoma
- Neoplasias Glandulares y Epiteliales
- Neoplasias Renales
- Carcinoma De Célula Renal
- Agentes antineoplásicos
- Agentes antineoplásicos inmunológicos
- Pembrolizumab
Otros números de identificación del estudio
- 3475-031
- 2014-002526-12 (Número EudraCT)
- MK-3475-031 (Otro identificador: Merck)
- KEYNOTE-031 (Otro identificador: Merck)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
SÍ
Descripción del plan IPD
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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. .