Neoadjuvant Immunotherapy ± Radiotherapy in MSI-H/dMMR Locally Advanced Colorectal Cancer

Официальное название

A Phase II Randomized Controlled Trial of Neoadjuvant Immunotherapy With or Without Radiotherapy in Locally Advanced Microsatellite Instability-High/Mismatch Repair-Deficient Colorectal Cancer

Обзор

This phase II clinical trial evaluates the efficacy and safety of three neoadjuvant regimens in patients with locally advanced microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) colorectal cancer (CRC): 1) Regimen A: Dual immune checkpoint blockade with nivolumab plus ipilimumab. 2) Regimen B: Nivolumab plus radiotherapy. 3) Regimen C: Nivolumab monotherapy. The primary objectives are to determine whether: 1) Dual immune checkpoint blockade (Regimen A) is superior to nivolumab monotherapy (Regimen C); and 2) Immunotherapy plus radiotherapy (Regimen B) is superior to nivolumab monotherapy (Regimen C). Methods: Participants will be randomized in a 1:1:1 ratio to one of the three arms. For patients with resectable tumors, surgical resection will be performed. In patients with low rectal cancer and poor prospects for sphincter preservation, a watch-and-wait (WW) strategy is an option if a clinical complete response (CR) is achieved following neoadjuvant therapy.

Вмешательства

• Препарат Nivolumab
  Nivolumab 240 mg every 2 weeks
• Препарат Ipilimumab (1mg/kg)
  Ipilimumab 1 mg/kg every 3 weeks
• Лучевая терапия PULSAR
  Irradiation targeted to the primary lesion (5 Gy per fraction, total 4 fractions, delivered every 3 weeks).
• Процедура Radical surgery
  Surgical resection will be performed in resectable cases.
• Другое Watch & wait
  For patients with low rectal cancer who are unable to preserve the anal sphincter, a watch-and-wait (WW) strategy can be considered if a clinical complete response (CR) is achieved.

Первичные конечные точки

• Complete regression (CR) rate [Срок оценки: 1 month after surgery or the completion of neoadjuvant therapy]

Вторичные конечные точки (7)

• R0 resection rate [Срок оценки: 1 month after surgery]
• Objective response rate (ORR) [Срок оценки: 6 months after the enrollment of the last subject]
• Event-free survival (EFS) [Срок оценки: 36 months after the enrollment of the last subject]
• Overall survival (OS) [Срок оценки: 36 months after the enrollment of the last subject]
• Toxicities [Срок оценки: From the time of enrollment, assessed up to 28 days after the last dose of study therapy]
• Surgical morbidity [Срок оценки: During or one month after surgery]
• Surgical mortality [Срок оценки: During or one month after surgery]

Критерии участия

Критерии включения

• Histopathologically confirmed primary colorectal adenocarcinoma.
• Radiographic assessment showed a stage II-III based on AJCC Stage 8th ed.
• At least 18 years old.
• MSI-H or dMMR.
• The Eastern Cooperative Oncology Group performance status (ECOG PS) score is 0 or 1.
• Physical state or organ function can tolerate the planned treatment of the study protocol.
• Agreed to sign written informed consent before recruitment.

Критерии исключения

• Previously received any antitumor therapy for the disease under study, including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, etc.
• Pregnancy or breastfeeding women.
• History of other malignancies within 5 years.
• Serious medical illness, such as severe mental disorders, cardiac disease, uncontrolled infection, etc.
• Immunodeficiency disease or long-term using of immunosuppressive agents.
• Allergic to any component of the therapy.
• Any other condition or disease that is not suitable to take the therapy included in the protocol.
• Concurrent participation in another clinical study, unless participating in an observational (non-interventional) clinical study or in the survival follow-up phase of an interventional study.
• Received any investigational drug or device treatment within 4 weeks prior to initial administration of the investigational drug.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Fudan University Shanghai Cancer Center — Шанхай

Идентификаторы

NCT: NCT07403877 · FDRT-2025-592-4741

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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