- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT03021993
Trial of Nivolumab as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer
Phase II Trial of Nivolumab, an Anti-PD-1 Monoclonal Antibody, as a Novel Neoadjuvant Pre-Surgical Therapy for Locally Advanced Oral Cavity Cancer
Descripción general del estudio
Descripción detallada
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
Contactos y Ubicaciones
Ubicaciones de estudio
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South Carolina
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Charleston, South Carolina, Estados Unidos, 29425
- Medical University of South Carolina
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
Newly diagnosed histologically proven locoregional OCSCC without evidence of distant metastases and a clinically determined T-stage of 2-4,
OR
Recurrent or persistent histologically proven locoregional OCSCC that was initially treated with surgery alone, and a clinically determined recurrent T-stage of 2-4.
Note - OCSCC includes the subsites of oral tongue, floor of mouth, gingiva, retromolar trigone, and buccal mucosa.
Note - To allow sufficient tumor tissue for the immunological analyses, patients with T-stage 1 OCSCC will be excluded
- Greater than or equal to 18 years of age
- ECOG performance status of 0 or 1
Screening labs must meet the following criteria and must be obtained within 14 days prior to registration:
- WBC > 2,000/µL
- Absolute Neutrophil Count >1,500/µL
- Platelets > 100 X 103/µL
- Hemoglobin > 9.0 g/dL
- Serum creatinine < 1.5 X ULN or CrCl > 40mL/min (if using the Cockcroft-Gault formula below):
Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL
- AST/ALT ≤ 3 x ULN
- Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL)
- Reproductive Status:
WOCBP must use appropriate method(s) of contraception. WOCBP should use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug.
Men receiving nivolumab and who are sexually active with WOCBP will be instructed to adhere to contraception with a failure rate of less than 1% per year for a period of 31 weeks after the last dose of investigational product.
WOCBP is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Menopause is defined clinically as 12 consecutive months of amenorrhea in a woman over 45.
Women of childbearing potential must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to registration Women who are not of childbearing potential (i.e., who are postmenopausal or surgically sterile) and azoospermic men, are not required to use contraception.
Exclusion Criteria:
- Prior immunotherapy or treatment with another anti PD 1 agent
- Prior chemotherapy including Cetuximab or radiation therapy
- Previous severe hypersensitivity reaction to another monoclonal antibody
- Women who are pregnant, lactating or expecting to conceive
- Men who are expecting to father children within the research period
- Known history of HIV or AIDS
- Positive test for HBV sAg or HCV antibody indicating acute or chronic infection
- Concomitant malignancies except cutaneous squamous cell carcinoma or basal cell carcinoma
- Unresectable primary tumor or regional disease; presence of distant metastases.
- History of pneumonitis or interstitial lung disease
- Active, known or suspected autoimmune disease. Note: Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger
- Presence of condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone or equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Nivolumab
Nivolumab (OPDIVO) will be administered every two weeks for up to four doses prior to surgery at 3mg/kg
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Nivolumab will be administered on days 1, 15 and 29.
If disease has progressed at day 29, the subject will proceed to surgery.
If a response or stable disease is present after the third dose, a fourth dose will be given on day 43, then the subject will proceed to surgery.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Objective response rate using pathological response
Periodo de tiempo: Time of surgery (day 36 or day 50)
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Objective response rate: the sum of patients with either a pCR defined as no invasive and no in situ residuals present in the surgical specimen or partial pathologic response defined at least a 30% reduction in the size of the lesion in the surgical specimen.
The reduction in size will be determined by comparing the pretreatment clinical measurements (the sum of the greatest axial measurement obtained with calipers at the time of initial evaluation) with the final pathologic measurements.
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Time of surgery (day 36 or day 50)
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
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Level of Treg cells in peripheral blood using immunostaining
Periodo de tiempo: Day 1 and time of surgery (day 36 or day 50)
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1. Levels of Treg cells in pre and post treatment peripheral blood will be evaluated using immunostaining for CD4 and flow cytometric analysis of Foxp3.
Differences will be calculated (absolute change and percentage change) between pre and post treatment measures.
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Day 1 and time of surgery (day 36 or day 50)
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Level of activated T-cells in peripheral blood
Periodo de tiempo: Day 1 and time of surgery (day 36 or day 50)
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2. Levels of activated T-cells in peripheral blood will be assessed using flow cytometry for expression of CD69, IFN γ, T-bet and ICOS in CD4+ cells.
Differences will be calculated (absolute change and percentage change) between pre and post treatment measures.
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Day 1 and time of surgery (day 36 or day 50)
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Level of immune stimulatory cytokines in peripheral blood
Periodo de tiempo: Day 1 and time of surgery (day 36 or day 50)
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3. Intratumoral immune activity assessed by levels of immune stimulatory cytokines including IL-2, IFN γ, and IL-12 or inhibitory cytokine, IL10 and TGF-beta, in OCSCC tumor lysates will be measured flow cytometrically by cytokine bead array.
Differences will be calculated (absolute change and percentage change) between pre and post treatment measures.
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Day 1 and time of surgery (day 36 or day 50)
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Expression of Th1 responses in CD4+ cells from peripheral blood
Periodo de tiempo: Day 1 and time of surgery (day 36 or day 50)
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Expression of IL-2 (Th1 responses) in CD4+ cells from peripheral blood of patients following PD-1 inhibition therapy will be compared between pre-treatment peripheral blood samples and post-treatment samples from the same patient.
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Day 1 and time of surgery (day 36 or day 50)
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Expression of Th2 responses in CD4+ cells from peripheral blood
Periodo de tiempo: Day 1 and time of surgery (day 36 or day 50)
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Expression of IIL 10 (Th2 responses) in CD4+ cells from peripheral blood of patients following PD-1 inhibition therapy will be compared between pre-treatment peripheral blood samples and post-treatment samples from the same patient.
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Day 1 and time of surgery (day 36 or day 50)
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Expression of CD8+ cells expressing granzyme B (ctolytic response) from peripheral blood
Periodo de tiempo: Day 1 and time of surgery (day 36 or day 50)
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2. Expression of CD8+ cells expressing granzyme B (cytolytic response) from peripheral blood of patients following PD-1 inhibition therapy will be compared between pre-treatment peripheral blood samples and post-treatment samples from the same patient.
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Day 1 and time of surgery (day 36 or day 50)
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: David Neskey, MD, Medical University of South Carolina
Publicaciones y enlaces útiles
Publicaciones Generales
- Knochelmann HM, Horton JD, Liu S, Armeson K, Kaczmar JM, Wyatt MM, Richardson MS, Lomeli SH, Xiong Y, Graboyes EM, Lentsch EJ, Hornig JD, Skoner J, Stalcup S, Spampinato MV, Garrett-Mayer E, O'Quinn EC, Timmers CD, Romeo MJ, Wrangle JM, Young MRI, Rubinstein MP, Day TA, Lo RS, Paulos CM, Neskey DM. Neoadjuvant presurgical PD-1 inhibition in oral cavity squamous cell carcinoma. Cell Rep Med. 2021 Oct 19;2(10):100426. doi: 10.1016/j.xcrm.2021.100426. eCollection 2021 Oct 19.
- Liu S, Knochelmann HM, Lomeli SH, Hong A, Richardson M, Yang Z, Lim RJ, Wang Y, Dumitras C, Krysan K, Timmers C, Romeo MJ, Krieg C, O'Quinn EC, Horton JD, Dubinett SM, Paulos CM, Neskey DM, Lo RS. Response and recurrence correlates in individuals treated with neoadjuvant anti-PD-1 therapy for resectable oral cavity squamous cell carcinoma. Cell Rep Med. 2021 Oct 19;2(10):100411. doi: 10.1016/j.xcrm.2021.100411. eCollection 2021 Oct 19.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Términos MeSH relevantes adicionales
- Neoplasias
- Neoplasias por sitio
- Neoplasias de Cabeza y Cuello
- Enfermedades Estomatognáticas
- Enfermedades de la Boca
- Neoplasias de la Boca
- Mecanismos moleculares de acción farmacológica
- Agentes antineoplásicos
- Agentes antineoplásicos inmunológicos
- Inhibidores de puntos de control inmunitarios
- Nivolumab
Otros números de identificación del estudio
- 102510
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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 Oral Cavity SCC
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Memorial Sloan Kettering Cancer CenterReclutamientoCáncer de cabeza y cuello | Carcinoma de células escamosas (SCC) de la cavidad oralEstados Unidos
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Rigshospitalet, DenmarkTerminadoCáncer bucal | Lengua SCCDinamarca
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University of California, DavisTerminadoPreocupaciones cognitivas subjetivas (SCC)Estados Unidos
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University of HohenheimTerminadoSeguridad después de la ingesta oral | Farmacocinética después de la ingesta oralAlemania
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University of HohenheimTerminadoSeguridad después de la ingesta oral | Farmacocinética después de la ingesta oralAlemania
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Novartis PharmaceuticalsReclutamientoCáncer de pulmón avanzado no pequeño con mutación de EGFR (NSCLC), NSCLC con mutación KRAS G12, cáncer de células escamosas de esófago (SCC), SCC de cabeza/cuello, melanomaPaíses Bajos, Corea, república de, España, Taiwán, Japón, Italia, Canadá, Estados Unidos, Singapur
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Seton Healthcare FamilyUniversity of Texas at Austin; Dell Medical School at The University of Texas...RetiradoCarcinoma de células basales (BCC) | Carcinoma de células escamosas (SCC)
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University of HohenheimGerman Federal Ministry of Economics and TechnologyTerminadoSeguridad después de la ingesta oral | Farmacocinética después de la ingesta oralAlemania
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Tufts Medical CenterDUSA Pharmaceuticals, Inc.TerminadoQueilitis actínica | Carcinoma de células escamosas in situ (SCC-is) | Carcinoma de células escamosas (SCC) | Terapia fotodinámica (TFD) | Cirugía de MohsEstados Unidos
Ensayos clínicos sobre Nivolumab
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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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Dan ZandbergBristol-Myers SquibbActivo, no reclutandoCarcinoma de células escamosas de cabeza y cuelloEstados Unidos
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IRCCS San RaffaeleBristol-Myers SquibbReclutamiento