- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT07796126
Sequential Toripalimab and Paclitaxel in Patients With Head and Neck Squamous Cell Cancer (HNSCC) and Poor Performance Status (HNSCC)
A Phase 2 Pilot Study of the Role of Sequential Immune Checkpoint Inhibitor Toripalimab and Chemotherapy Paclitaxel in Patients With HNSCC and ECOG Performance Score of 2
The goal of this clinical trial is to learn if the drug Toripalimab can prime the tumor to optimize response to Paclitaxel in HNSCC patients with a decrease performance status in a way that make both drugs well tolerated and improve partial or complete response rate over each treatment. The main questions it aims to answer are:
- What is the response rate of the cancer to paclitaxel after priming with toripalimab
- What is the time to progression if we continue to cycle between toripalimab and paclitaxel
- What is the impact on the patient's quality of life and overall survival
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
Toripalimab treatment will be administered on an outpatient basis. Toripalimab will be given in the clinic on Day 1. Intravenous (IV) infusions will be given every three weeks thereafter for the first seven weeks of the study. Administration follows standard of care.
Paclitaxel treatment will be administered on an outpatient basis as per standard of care once weekly for a total of eight weeks during Weeks 8-15 of each cycle. Premedication and administration follow standard of care. After eight weeks of chemotherapy, the participant finishes the cycle with two weeks of rest (no treatment).
This will be repeated for a total of 51 weeks total of 3 cycles (each cycle is 17 weeks) We will study sequential ICI and CT on HNSCC, and the impact on quality of life in addition to studying the tumor microenvironment. Participants undergo an optional biopsy before and after eight weeks of weekly paclitaxel. To explore the cytotoxic signature, we will calculate the enrichment scores for canonical cytotoxic markers (GZMA, GZMB, GZMK, GNLY, IFNG, PRF1 and NKG7). To estimate the signature of collagen formation, we will calculate enrichment scores using the gene lists from the REACTOME_COLLAGEN_FORMATION pathway (msigdb.v7.5.1.symbols.gmt; https://www.gsea-msigdb.org/gsea/index.jsp). To explore the cell type contexts, we will perform principal component analysis (PCA) and then uniform manifold approximation and projection (UMAP) using the RunPCA and RunUMAP functions based on the cell type proportion inferred by spatial transcriptomics deconvolution (STRIDE). Results will be summarized using descriptive statistics, including mean, median, standard deviation, range, count, and percentage, as appropriate.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Ammar Sukari, M.D.
- Número de teléfono: 313-576-8709
- Correo electrónico: sukarim@karmanos.org
Ubicaciones de estudio
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Michigan
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Detroit, Michigan, Estados Unidos, 48201
- Karmanos Cancer Institute
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Contacto:
- Ammar Sukari, M.D.
- Número de teléfono: 313-576-8709
- Correo electrónico: sukarim@karmanos.org
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Participants must have histologically confirmed HNSCC deemed to be metastatic or incurable by the treating physician. Participants can have incurable disease at presentation or have been treated with definitive curable surgical resection, chemoradiotherapy (CRT), or both, then relapsed with non-curable disease. Participants diagnosed with HNSCC stage IV-C or metastatic/non-resectable, relapsed disease are eligible for this study
- Participant must have measurable disease, defined by RECIST v1.1.
- Participant must be able to understand a written informed consent document and be willing to sign it.
- Participants must be 18 years of age or older.
- Participant must have a life expectancy of at least six months.
- Participant must have an ECOG performance score of 2.
Participant must have:
- Total bilirubin ≤ 3 times upper limit of normal (ULN)
- Hemoglobin > 8 g/dL. Transfusion is permitted
- Absolute neutrophil count (ANC) > 1.0 K/mm3. Granulocyte colony-stimulating factor (G-CSF) is NOT permitted
- Paclitaxel has known embryo- and fetotoxic effects. Therefore, women of childbearing potential must agree to avoid becoming pregnant and male participants should avoid impregnating a female partner and donating sperm starting at initiation of treatment up until at least 30 days after last dose of toripalimab or paclitaxel.
Exclusion Criteria:
- Participants with known untreated brain metastases will be excluded from this clinical trial. Stable brain metastases will be allowed, and it will be confirmed by stable brain MRI with and without contrast within 8 weeks of signing consent.
- Participants with uncontrolled chronic obstructive pulmonary disease (COPD), heart disease, or autoimmune disease, in the opinion of the treating physician.
- Participants who are taking any other investigational drugs.
Participants who are taking prednisone or equivalent steroid >10 mg per day prior to the start of treatment.
- The washout period is at the treating physician's discretion.
- Once participants are on study, they may be treated with steroids and other immunosuppressants per standard of care.
- Participants with a history of allergic reactions attributed to toripalimab, paclitaxel, or medicines containing Kolliphor ELP (Polyoxyl 35 Castor Oil, NF).
- Participants who are pregnant or breastfeeding. If a breastfeeding participant would like to be part of this study, breastfeeding must be discontinued.
- Participants who have end-stage renal failure are eligible for this study unless they have had a kidney transplant.
- Participants that do not agree to be followed according to the study protocol or have cognitive or physical inability to follow the treatment plan.
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: Toripalimab plus Paclitaxel
Toripalimab 240mg on weeks 1, 4 and 7 in combination with Paclitaxel 80mg/m2 weeks 8-15 with a rest on Weeks 16-17 for 3 cycles.
One cycle equals 17 weeks
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Toripalimab 240mg intravenously every three weeks on weeks 1, 4 and 7 of a 17 week cycle.
Otros nombres:
Paclitaxel 80mg/m2 intravenously over weekly for 8 weeks on weeks 8-15 of each cycle times 3 cycles
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Objective Response Rate (ORR)
Periodo de tiempo: Up to 1 year after treatment initiation
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The ORR is calculated as the proportion of participants with complete response (CR) or partial response (PR) per RECIST v1.1 among all treated participants.
CR is the disappearance of all lesions; PR is at least a 30% decrease in the sum of diameters of target lesions.
The two-sided 95% confidence interval (CI) for ORR will be estimated using Clopper-Pearson's method.
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Up to 1 year after treatment initiation
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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: Up to 2 years after treatment initiation
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The OS is the length of time from the start of treatment that participants are still alive.
The distribution of OS will be graphically summarized using a Kaplan-Meier (KM) curve with corresponding median and two-sided 95% CIs computed using KM estimates.
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Up to 2 years after treatment initiation
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Progression Free Survival (PFS)
Periodo de tiempo: Up to 1 year after treatment initiation
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PFS is defined as the time duration from treatment start to progression or death from any cause, whichever occurs first.
Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions.
The distribution of PFS will be graphically summarized using a KM curve with corresponding median and two-sided 95% CIs computed using KM estimates.
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Up to 1 year after treatment initiation
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Duration of Response (DOR)
Periodo de tiempo: Up to 2 years after treatment initiation
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DOR is the length of time that a tumor continues to respond to treatment without the cancer growing or spreading.
The distribution of DOR will be graphically summarized using a KM curve with corresponding median and two-sided 95% CIs computed using KM estimates.
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Up to 2 years after treatment initiation
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Impact on Quality of Life (QOL)
Periodo de tiempo: Up to 1 year after treatment initiation
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QOL will be measured using the Functional Assessment of Cancer Therapy for Head & Neck cancer (FACT-H&N).
The distribution of QOL will be assessed, and if necessary, a data transformation will be applied to meet normality assumptions.
Longitudinal QOL will be summarized using the mean, median, standard deviation (SD), range, and 95% CI across all time points.
Minimally important differences (MID) in FACT scores will be determined; for FACT-General the MID is 3 to 7 and for all the subscales the MID is 2 to 3.
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Up to 1 year after treatment initiation
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Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Ammar Sukari, M.D., Barbara Ann Karmanos Cancer Institute
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
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 por sitio
- Neoplasias
- Neoplasias por tipo histológico
- Neoplasias Glandulares y Epiteliales
- Carcinoma
- Carcinoma De Células Escamosas
- Carcinoma de células escamosas de cabeza y cuello
- Neoplasias de Cabeza y Cuello
- Químicos orgánicos
- Hidrocarburos
- Cicloparafinas
- Hidrocarburos, alicíclicos
- Hidrocarburos, cíclico
- Terpenos
- Taxaides
- Ciclodecanos
- Diterpenos
- Paclitaxel
- toripalimab
Otros números de identificación del estudio
- 2025-066 (Otro identificador: Turkish Medicines and Medical Devices Agency Clinical Trial Authorization Number)
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.
producto fabricado y exportado desde los EE. UU.
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