Intratumoral Injection of Recombinant Human Endostatin Adenovirus (EDS01) for the Treatment of Recurrent or Metastatic Head and Neck Tumors (EDS01 HN)
A Phase I Clinical Trial of Intratumoral Injection of Recombinant Human Endostatin Adenovirus (EDS01) Combined With Toripalimab for the Treatment of Recurrent or Metastatic Head and Neck Tumors
This single-center, Phase 1 study is evaluating the safety, tolerability, and preliminary antitumor activity of recombinant human endostatin adenovirus injection (EDS01) given by intratumoral injection in combination with toripalimab in adults with recurrent or metastatic head and neck tumors, including nasopharyngeal carcinoma, whose disease has progressed after platinum-based systemic therapy or who are not suitable for further platinum treatment.
A total of 9 participants will be enrolled in 3 planned dose groups of EDS01. EDS01 will be injected directly into an accessible tumor lesion on Days 0 and 7, and toripalimab 240 mg will be administered intravenously on Day 1 of each treatment cycle for up to 4 cycles, unless disease progression or unacceptable toxicity occurs. The study will evaluate treatment-related adverse events as well as preliminary efficacy outcomes, including tumor response, disease control, and time to progression, using clinical assessments, laboratory tests, imaging, and follow-up after treatment.
Descripción general del estudio
Estado
Descripción detallada
Patients with recurrent or metastatic head and neck tumors, including nasopharyngeal carcinoma, have limited treatment options after failure of platinum-based therapy. Anti-programmed cell death protein 1 (PD-1) therapy is an established later-line treatment option in this setting. EDS01 is a recombinant human endostatin adenovirus injection designed for intratumoral administration. By delivering the human endostatin gene into tumor cells, EDS01 is intended to support sustained local expression of endostatin and inhibit tumor angiogenesis. Head and neck lesions are often accessible for direct intratumoral injection and serial local assessment, which makes this disease setting suitable for evaluation of this approach. Prior early-phase clinical experience with EDS01 in advanced head and neck tumors showed that the main observed toxicities were fever, injection-site pain, and flu-like symptoms, without dose-limiting toxicity or serious adverse events at the studied dose levels, and preliminary antitumor activity was observed. These findings support further evaluation of EDS01 in combination with PD-1 blockade.
This single-center Phase 1 study is designed to evaluate the safety, tolerability, and preliminary antitumor activity of EDS01 in combination with toripalimab in adults with recurrent or metastatic head and neck tumors who have previously received platinum-based treatment or demonstrated platinum insensitivity or intolerance, and who have an injectable tumor lesion. The study will explore planned EDS01 dose levels in combination with fixed-dose toripalimab in order to characterize the safety profile of the regimen and identify whether the combination is feasible for further clinical development.
Study evaluations include clinical assessments, physical examinations, laboratory testing, and monitoring of adverse events and serious adverse events. Tumor response will be assessed radiographically according to RECIST version 1.1, including evaluation of objective response, disease control, and time to progression. Additional translational and exploratory assessments include anti-adenovirus antibody testing, serum endostatin measurement, and selected monitoring related to environmental shedding after intratumoral administration. After treatment, participants will enter follow-up and be assessed every 3 months until disease progression or death.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: nan lin, MD
- Número de teléfono: +8618708305692
- Correo electrónico: nanishard@gmail.com
Ubicaciones de estudio
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China
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Chengdu, China, Porcelana, 610041
- Reclutamiento
- West China Hospital
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Contacto:
- Xuelei Ma
- Número de teléfono: 18708305692
- Correo electrónico: drmaxuelei@gmail.com
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
Adults aged 18 to 65 years. Histologically or cytologically confirmed recurrent or metastatic head and neck tumor.
Previously received at least 1 standard platinum-based systemic chemotherapy regimen for recurrent/metastatic disease, or had platinum-insensitive or platinum-intolerant disease after prior curative-intent treatment.
Not suitable for surgery or radiotherapy. At least 1 target lesion suitable for intratumoral injection of recombinant human endostatin adenovirus injection.
At least 1 measurable lesion with diameter ≥2 cm on imaging, according to RECIST version 1.1.
No chemotherapy, radiotherapy, biologic antitumor therapy, or antiviral therapy within 4 weeks before enrollment.
Estimated life expectancy of at least 12 weeks. ECOG performance status 0 to 1. Male or female participants of childbearing potential must agree to use reliable contraception during treatment and for at least 6 months after treatment.
Recovery of prior treatment-related toxicities to NCI CTCAE grade 1 or baseline, with screening laboratory results within 1 week before enrollment meeting protocol requirements: ANC ≥1.5×10^9/L, platelet count ≥80×10^9/L, total bilirubin ≤1.5 × ULN, ALT and AST ≤2 × ULN, and coagulation parameters ≤1.25 × ULN.
Willing and able to provide written informed consent.
Exclusion Criteria:
Known allergy to the study drugs. Lesions involving major blood vessels or nerves and therefore unsuitable for local injection.
Receiving radiotherapy to the study lesion at the same time. Prior anti-angiogenic therapy. Receiving immunosuppressive therapy or systemic corticosteroids for immunosuppressive purposes at a dose greater than prednisone 10 mg/day (or equivalent) within 2 weeks before enrollment.
Active autoimmune disease or history of autoimmune disease. Congenital or acquired immunodeficiency. Risk of major nasopharyngeal hemorrhage or deep nasopharyngeal ulceration. Severe coagulation disorder or bleeding tendency. Severe uncontrolled medical disease or myocardial infarction within 3 months before enrollment.
Acute infection. Pregnant or breastfeeding women. Any condition that, in the investigator's judgment, makes the participant unsuitable for enrollment.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- 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: EDS01 1.0×10^11 VP + Toripalimab
Participants receive intratumoral EDS01 1.0×10^11 viral particles (VP) on Days 0 and 7 plus toripalimab 240 mg by intravenous infusion on Day 1 of each 21-day cycle.
Treatment may continue for up to 4 cycles unless disease progression or unacceptable toxicity occurs.
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Recombinant human endostatin adenovirus injection (EDS01) is administered by intratumoral injection into an accessible tumor lesion on Days 0 and 7 of each 21-day cycle.
Three planned dose levels are evaluated across study cohorts: 1.0×10^11 VP.
Treatment may continue for up to 4 cycles unless disease progression or unacceptable toxicity occurs.
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Experimental: EDS01 5.0×10^11 VP + Toripalimab
Participants receive intratumoral EDS01 5.0×10^11 viral particles (VP) on Days 0 and 7 plus toripalimab 240 mg by intravenous infusion on Day 1 of each 21-day cycle.
Treatment may continue for up to 4 cycles unless disease progression or unacceptable toxicity occurs.
|
Recombinant human endostatin adenovirus injection (EDS01) is administered by intratumoral injection into an accessible tumor lesion on Days 0 and 7 of each 21-day cycle.
Three planned dose levels are evaluated across study cohorts: 5.0×10^11 VP.
Treatment may continue for up to 4 cycles unless disease progression or unacceptable toxicity occurs.
|
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Experimental: EDS01 1.0×10^12 VP + Toripalimab
Participants receive intratumoral EDS01 1.0×10^12 viral particles (VP) on Days 0 and 7 plus toripalimab 240 mg by intravenous infusion on Day 1 of each 21-day cycle.
Treatment may continue for up to 4 cycles unless disease progression or unacceptable toxicity occurs.
|
Recombinant human endostatin adenovirus injection (EDS01) is administered by intratumoral injection into an accessible tumor lesion on Days 0 and 7 of each 21-day cycle.
Three planned dose levels are evaluated across study cohorts: 1.0×10^12 VP.
Treatment may continue for up to 4 cycles unless disease progression or unacceptable toxicity occurs.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Incidence of adverse events (AEs) and serious adverse events (SAEs)
Periodo de tiempo: From signing informed consent through 1 month after the end of treatment (up to 16 weeks).
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Number and percentage of participants with adverse events (AEs), serious adverse events (SAEs), treatment-related adverse events, and clinically significant abnormal laboratory findings.
Adverse events will be graded according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC), version 4.0.
Safety evaluation will also include physical examination findings and environmental shedding monitoring related to intratumoral administration of EDS01.
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From signing informed consent through 1 month after the end of treatment (up to 16 weeks).
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Objective response rate of target lesions
Periodo de tiempo: From baseline until disease progression or end of treatment, whichever occurs first (up to 3 years).
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Proportion of participants with complete response (CR) or partial response (PR) in target lesions.
Tumor response will be assessed according to RECIST version 1.1.
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From baseline until disease progression or end of treatment, whichever occurs first (up to 3 years).
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Disease control rate of target lesions
Periodo de tiempo: From baseline until disease progression or end of treatment, whichever occurs first (up to 3 years).
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Proportion of participants with complete response (CR), partial response (PR), or stable disease (SD) in target lesions, assessed according to RECIST version 1.1.
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From baseline until disease progression or end of treatment, whichever occurs first (up to 3 years).
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Overall objective response rate of all lesions
Periodo de tiempo: From baseline until disease progression or end of treatment, whichever occurs first (up to 3 years).
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Proportion of participants with complete response (CR) or partial response (PR) in overall lesions, assessed according to RECIST version 1.1.
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From baseline until disease progression or end of treatment, whichever occurs first (up to 3 years).
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Time to progression (TTP)
Periodo de tiempo: From enrollment until first documented disease progression; participants will be followed every 3 months after treatment until progression or death. Up to 3 years from enrollment.
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Time from enrollment to the first documented disease progression.
Deaths before progression will be censored.
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From enrollment until first documented disease progression; participants will be followed every 3 months after treatment until progression or death. Up to 3 years from enrollment.
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in serum anti-adenovirus IgG
Periodo de tiempo: From signing informed consent through 1 month after the end of treatment (up to approximately 16 weeks).
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Change in serum anti-adenovirus (ADV) IgG from baseline to post-baseline assessments, measured by ELISA.
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From signing informed consent through 1 month after the end of treatment (up to approximately 16 weeks).
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Colaboradores e Investigadores
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
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
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 2025(395)
Plan de datos de participantes individuales (IPD)
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Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
Información sobre medicamentos y dispositivos, documentos del estudio
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