Short-Course Radiotherapy Followed by CAPOX With or Without Iparomlimab and Tuvonralimab in pMMR/MSS Locally Advanced Rectal Cancer (SCRIT)
Short-Course Radiotherapy Followed by CAPOX With or Without Iparomlimab and Tuvonralimab in pMMR/MSS Locally Advanced Rectal Cancer (SCRIT): A Multicenter Phase III Randomized Controlled Trial
This multicenter, randomized, controlled, phase III trial evaluates whether adding iparomlimab and tuvonralimab injection to CAPOX consolidation chemotherapy after short-course radiotherapy improves tumor response in patients with treatment-naive, proficient mismatch repair/microsatellite-stable (pMMR/MSS) locally advanced rectal adenocarcinoma. Eligible patients will be randomly assigned in a 1:1 ratio to receive short-course radiotherapy followed by CAPOX plus iparomlimab and tuvonralimab, or short-course radiotherapy followed by CAPOX alone.
After total neoadjuvant therapy, patients with a clinical complete response may undergo a Watch-and-Wait strategy, whereas other patients will undergo total mesorectal excision according to standard clinical practice. The primary endpoint is complete response rate, defined as pathologic complete response after surgery or clinical complete response sustained for more than 1 year. Secondary endpoints include 3-year relapse-free survival, 3-year overall survival, sphincter preservation rate, and grade 3-4 acute adverse events. Exploratory analyses will assess tissue and blood biomarkers associated with treatment response.
Descripción general del estudio
Estado
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase 3
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Jinbo Yue Doctor
- Número de teléfono: 0531-67626442
- Correo electrónico: jbyue@sdfmu.edu.cn
Ubicaciones de estudio
-
-
Shandong
-
Jinan, Shandong, Porcelana, 0531
- Reclutamiento
- Shandong Cancer Hospital And Institute
-
Contacto:
- Jinbo Yue Doctor, Doctor
- Número de teléfono: 0531-67626442
- Correo electrónico: jbyue@sdfmu.edu.cn
-
Contacto:
- Jinbo Yue Doctor, Doctor
- Correo electrónico: jbyue@sdfmu.edu.cn
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:
- Patients aged 18-75 years with histologically confirmed pMMR/MSS rectal adenocarcinoma are eligible if they have MRI-defined clinical stage II or III disease according to AJCC 8th edition, tumor located within 12 cm from the anal verge, and at least one high-risk feature, including cT4b, cN2, EMVI positivity, MRF positivity, lateral lymph node positivity, tumor deposits, or tumor located ≤5 cm from the anal verge. Patients must have no distant metastasis, ECOG performance status 0-1, life expectancy greater than 6 months, and adequate hematologic, hepatic, and renal function
Exclusion Criteria:
- active or prior autoimmune disease requiring systemic treatment, use of immunosuppressive therapy or systemic corticosteroids at immunosuppressive doses, severe hypersensitivity to monoclonal antibodies, uncontrolled cardiac disease, significant coagulopathy or bleeding tendency, active infection, interstitial lung disease or severe pulmonary dysfunction, HIV infection or active hepatitis, prior or concurrent malignancy except specified cured cancers, recent investigational drug use, planned use of other systemic antitumor therapy during the study, pregnancy or breastfeeding, and any other condition judged by the investigator to make participation unsuitable.
Plan de estudios
¿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: Treatment
Short-Course Radiotherapy + CAPOX + Iparomlimab and Tuvonralimab Radiotherapy: Short-course external-beam radiotherapy will be delivered to the rectal primary tumor and corresponding lymphatic drainage regions using IMRT or VMAT. The prescribed dose is 25 Gy in 5 fractions over 1 week. No concurrent chemotherapy will be administered during short-course radiotherapy. Consolidation treatment: Iparomlimab and tuvonralimab injection will be administered at 5 mg/kg by intravenous infusion every 21 days for 6 cycles. CAPOX chemotherapy will consist of oxaliplatin 130 mg/m² intravenously on day 1 plus capecitabine 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle, for 6 cycles. |
Short-course external-beam radiotherapy will be delivered to the rectal primary tumor and corresponding lymphatic drainage regions using IMRT or VMAT.
The prescribed dose is 25 Gy in 5 fractions over 1 week.
No concurrent chemotherapy will be administered during short-course radiotherapy.
Iparomlimab and tuvonralimab injection will be administered at 5 mg/kg by intravenous infusion every 21 days for 6 cycles.
CAPOX chemotherapy will consist of oxaliplatin 130 mg/m² intravenously on day 1 plus capecitabine 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle, for 6 cycles.
|
|
Comparador activo: Control
Short-Course Radiotherapy + CAPOX Radiotherapy: Short-course external-beam radiotherapy will be delivered to the rectal primary tumor and corresponding lymphatic drainage regions using IMRT or VMAT. The prescribed dose is 25 Gy in 5 fractions over 1 week. No concurrent chemotherapy will be administered during short-course radiotherapy. Consolidation treatment: CAPOX chemotherapy will consist of oxaliplatin 130 mg/m² intravenously on day 1 plus capecitabine 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle, for 6 cycles. |
Short-course external-beam radiotherapy will be delivered to the rectal primary tumor and corresponding lymphatic drainage regions using IMRT or VMAT.
The prescribed dose is 25 Gy in 5 fractions over 1 week.
No concurrent chemotherapy will be administered during short-course radiotherapy.
CAPOX chemotherapy will consist of oxaliplatin 130 mg/m² intravenously on day 1 plus capecitabine 1000 mg/m² orally twice daily on days 1-14 of each 21-day cycle, for 6 cycles.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Complete Response (CR) Rate
Periodo de tiempo: From randomization to completion of definitive response assessment, including surgical pathological assessment after total neoadjuvant therapy or confirmation of sustained clinical complete response after at least 12 months of Watch-and-Wait follow-up
|
Complete response rate is defined as the proportion of patients who achieve either pathologic complete response (pCR) after surgery or sustained clinical complete response (cCR) for more than 1 year during Watch-and-Wait follow-up.
|
From randomization to completion of definitive response assessment, including surgical pathological assessment after total neoadjuvant therapy or confirmation of sustained clinical complete response after at least 12 months of Watch-and-Wait follow-up
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
3-Year Relapse-Free Survival (RFS)
Periodo de tiempo: From randomization to the first documented disease relapse/recurrence, death from any cause, or 3 years after randomization, whichever occurs first.
|
Relapse-free survival is defined as the time from randomization to the first evidence of disease relapse or recurrence.
Patients without relapse/recurrence or death will be censored at the date of last disease assessment.
|
From randomization to the first documented disease relapse/recurrence, death from any cause, or 3 years after randomization, whichever occurs first.
|
|
3-Year Overall Survival (OS)
Periodo de tiempo: From randomization to death from any cause or 3 years after randomization, whichever occurs first.
|
Overall survival is defined as the time from randomization to death from any cause.
Patients who are alive at the time of analysis will be censored at the date of last known survival follow-up.
|
From randomization to death from any cause or 3 years after randomization, whichever occurs first.
|
|
Sphincter Preservation Rate
Periodo de tiempo: From randomization to completion of definitive surgery, or to at least 12 months after initiation of Watch-and-Wait follow-up for patients who do not undergo surgery; approximately up to 18-24 months after randomization.
|
Sphincter preservation rate is defined as the proportion of patients who successfully preserve anal sphincter structure and function and avoid permanent colostomy.
|
From randomization to completion of definitive surgery, or to at least 12 months after initiation of Watch-and-Wait follow-up for patients who do not undergo surgery; approximately up to 18-24 months after randomization.
|
|
Incidence of Grade 3-4 Acute Adverse Events
Periodo de tiempo: From the start of study treatment to 30 days after completion of neoadjuvant treatment.
|
Acute adverse events will be graded and recorded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.
The incidence of grade 3-4 acute adverse events will be summarized by treatment arm.
|
From the start of study treatment to 30 days after completion of neoadjuvant treatment.
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Jinbo Yue, Doctor, study principal investigator
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
Otros números de identificación del estudio
- SDZLEC2026-051-002
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. .