Pucotenlimab, Lenvatinib, and SBRT Before Surgery for Localized Clear Cell Renal Cell Carcinoma (PLS-NEO-RCC)
A Single-Arm Phase II Study of Neoadjuvant Pucotenlimab, Lenvatinib, and Stereotactic Body Radiotherapy in Patients With Localized Clear Cell Renal Cell Carcinoma and High-Risk Partial Nephrectomy
This single-arm Phase II study will evaluate the efficacy and safety of neoadjuvant pucotenlimab, lenvatinib, and stereotactic body radiotherapy (SBRT) in adults with localized clear cell renal cell carcinoma who are candidates for partial nephrectomy but have tumors that make the operation technically difficult. Approximately 24 participants will receive up to six cycles of pucotenlimab with daily lenvatinib. SBRT will be delivered to the primary renal tumor during neoadjuvant treatment. Surgery is planned after neoadjuvant treatment. The primary outcome is objective response rate.
Descripción general del estudio
Estado
Estado
Condiciones
Condiciones
Intervención / Tratamiento
Intervención / Tratamiento
Descripción detallada
This is a prospective, single-arm Phase II study using a Simon optimal two-stage design. The study plans to enroll 24 participants. In stage 1, eight participants will be enrolled; if no more than three have an objective response, the study will stop for futility. Otherwise, 16 additional participants will be enrolled.
Participants will receive pucotenlimab 200 mg by intravenous infusion every 3 weeks for up to six cycles and lenvatinib 12 mg orally once daily during neoadjuvant treatment. SBRT will be delivered to the primary renal tumor at a total dose of 40 Gy in five fractions after completion of the second pucotenlimab cycle and before the fourth cycle. Tumor imaging will be performed during neoadjuvant treatment. Surgery, preferably partial nephrectomy when feasible, is planned 2 to 4 weeks after the sixth pucotenlimab cycle. Efficacy, surgical outcomes, and adverse events will be evaluated.
Tipo de estudio
Tipo de estudio
Inscripción (Estimado)
Inscripción
Fase
Fase
- Fase 2
Contactos y Ubicaciones
Estudio Contacto
Estudio Contacto
- Nombre: Yulu Peng, Doc
- Número de teléfono: 02087342318
- Correo electrónico: pengyl1@sysucc.org.cn
Criterios de participación
Criterio de elegibilidad
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Voluntary written informed consent.
- Age 18 years or older.
- ECOG performance status of 0 or 1.
- Life expectancy of at least 3 months.
- Preoperative biopsy confirming clear cell renal cell carcinoma or renal cell carcinoma with a predominant clear cell component.
- Willingness to undergo partial nephrectomy.
- A localized renal tumor for which partial nephrectomy is indicated but technically difficult: a 4-7 cm hilar tumor; a 4-7 cm tumor that is at least 75% endophytic; or a tumor larger than 7 cm.
- At least one measurable lesion suitable for repeated, accurate measurement.
- Adequate organ function: absolute neutrophil count ≥1.5 × 10^9/L; platelet count ≥100 × 10^9/L; hemoglobin ≥90 g/L; total bilirubin ≤1.5 × upper limit of normal (ULN); ALT and AST ≤2.5 × ULN, or ≤5 × ULN for participants with liver metastases; albumin ≥28 g/L; INR and APTT ≤1.5 × ULN. No blood component transfusion or hematopoietic growth-factor support is permitted within 2 weeks before treatment.
- Willingness and ability to comply with study visits, treatment, laboratory assessments, and other study requirements.
Exclusion Criteria:
- Lymph node metastasis or metastatic renal cell carcinoma.
- Tumor encasement of the renal artery, tumor thrombus in the renal vein, or diffuse tumor growth without a clear boundary from normal renal parenchyma.
- Inability to tolerate general anesthesia according to the preoperative assessment.
- Severe cardiovascular or cerebrovascular disease, or uncontrolled hypertension or diabetes.
- Long-term immunosuppressive therapy after organ transplantation, or current use of immunosuppressive medication.
- Active infection or fever.
- T-cell lymphoma or multiple myeloma.
- Concurrent malignancy, current treatment for another benign or malignant tumor, or a history of another malignancy within the previous 6 months.
- Use of herbal medicines with an anticancer indication or systemic immunomodulatory agents, including thymosin, interferon, or interleukin, within 14 days before the first study treatment; local use to control pleural effusion is permitted.
- Active or potentially recurrent autoimmune disease, except vitiligo, alopecia, psoriasis, or eczema not requiring systemic therapy; hypothyroidism due to autoimmune thyroiditis requiring only a stable dose of hormone replacement; or type 1 diabetes requiring only a stable dose of insulin.
- Concurrent enrollment in another interventional clinical study, except participation in its follow-up period; participation in a noninterventional observational study is permitted.
- Known psychiatric illness or a history of drug abuse, alcohol abuse, or illicit drug use.
- Pregnancy or breastfeeding.
- Any other disease, treatment, or laboratory abnormality that may confound the study results, prevent full participation, or make participation contrary to the participant's best interests.
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)
Número de brazos
Armas e Intervenciones
Grupo de participantes/brazoGrupo de participantes/brazo |
Intervención / TratamientoIntervención / Tratamiento |
|---|---|
|
Experimental: Pucotenlimab Plus Lenvatinib and SBRT
Participants will receive neoadjuvant pucotenlimab 200 mg intravenously every 3 weeks for up to six cycles and lenvatinib 12 mg orally once daily. SBRT at 40 Gy in five fractions will be delivered to the primary renal tumor after cycle 2 and before cycle 4. Surgery is planned after neoadjuvant treatment, with partial nephrectomy preferred when feasible. |
200 mg administered by intravenous infusion once every 3 weeks for up to six cycles. Lenvatinib 12 mg taken orally once daily during neoadjuvant treatment; treatment is stopped at least 3 days before surgery. SBRT to the primary renal tumor at a total dose of 40 Gy in five fractions, delivered after completion of pucotenlimab cycle 2 and before cycle 4. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Objective Response Rate (ORR)
Periodo de tiempo: From baseline through completion of neoadjuvant treatment, approximately 18 weeks.
|
Percentage of participants with a complete response or partial response of the primary renal tumor according to RECIST version 1.1 during neoadjuvant treatment. |
From baseline through completion of neoadjuvant treatment, approximately 18 weeks.
|
Medidas de resultado secundarias
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Major Pathological Response (MPR) Rate
Periodo de tiempo: At surgery, approximately 20 to 22 weeks after treatment initiation.
|
Percentage of participants with major pathological response in the resected primary tumor. |
At surgery, approximately 20 to 22 weeks after treatment initiation.
|
|
Partial Nephrectomy Success Rate
Periodo de tiempo: At surgery, approximately 20 to 22 weeks after treatment initiation.
|
Percentage of participants who undergo partial nephrectomy after neoadjuvant treatment. |
At surgery, approximately 20 to 22 weeks after treatment initiation.
|
|
R0 Resection Rate
Periodo de tiempo: At surgery, approximately 20 to 22 weeks after treatment initiation.
|
Percentage of surgically treated participants with microscopically negative surgical margins. |
At surgery, approximately 20 to 22 weeks after treatment initiation.
|
|
Surgical Complications
Periodo de tiempo: From surgery through the 3-month postoperative visit.
|
Number and percentage of participants with surgical complications, including bleeding and urinary leakage. |
From surgery through the 3-month postoperative visit.
|
|
Adverse Events
Periodo de tiempo: From informed consent through 30 days after the last dose of study medication.
|
Number and percentage of participants with adverse events, graded according to NCI-CTCAE version 4.0. |
From informed consent through 30 days after the last dose of study medication.
|
Colaboradores e Investigadores
Patrocinador
Patrocinador
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Inicio del estudio
Finalización primaria (Estimado)
Finalización primaria
Finalización del estudio (Estimado)
Finalización del estudio
Fechas de registro del estudio
Enviado por primera vez
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Publicado por primera vez
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización publicada
Última actualización enviada que cumplió con los criterios de control de calidad
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Enfermedades urogenitales
- Neoplasias urogenitales
- Neoplasias por sitio
- Neoplasias
- Enfermedades urogenitales masculinas
- Enfermedades Renales
- Enfermedades urológicas
- Enfermedades urogenitales femeninas
- Enfermedades urogenitales femeninas y complicaciones del embarazo
- Neoplasias por tipo histológico
- Neoplasias Glandulares y Epiteliales
- Adenocarcinoma
- Neoplasias Urológicas
- Carcinoma
- Neoplasias Renales
- Carcinoma De Célula Renal
- Técnicas de investigación
- Terapéutica
- Procedimientos quirúrgicos, operativo
- Radioterapia
- Técnicas estereotáxicas
- Procedimientos neurociruúrgicos
- Radiocirugía
- lenvatinib
Otros números de identificación del estudio
Otros números de identificación del estudio
- 2024-FXY-321-Urology
- 2024-FXY-321-Urology (Otro identificador: Sun Yat-sen University cancer center)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Individual participant data will not be shared because this small study collects sensitive clinical, imaging, and molecular data that could increase the risk of participant re-identification. Study results will be reported in aggregate form.
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.
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