Fruquintinib Combined With Sintilimab ± Radiotherapy for Third-line Treatment of Colorectal Cancer With Liver Metastases

Официальное название

Fruquintinib Combined With Sintilimab ± Radiotherapy for Third-line Treatment of Colorectal Cancer With Liver Metastases: A Randomized, Controlled, Multicenter Phase II Trial

Обзор

Colorectal cancer (CRC) is a significant cause of morbidity and mortality worldwide. Its early clinical manifestations are often subtle, leading to late-stage diagnosis in about 30% of cases with distant metastases. Liver metastases are widespread and associated with poor prognosis, especially in terms of response to immunotherapy. This prospective study will evaluate the efficacy of combined therapy involving sintilimab, fruquintinib, and radiotherapy in CRC with liver metastases. The primary objectives are to assess progression-free survival, overall survival, and treatment response rates. This study aims to provide valuable insights into optimizing third-line and subsequent therapies for CRC with liver metastases by elucidating the efficacy and safety of this combined treatment approach.

Подробное описание

CRC is a significant cause of morbidity and mortality worldwide. Its early clinical manifestations are often subtle, leading to late-stage diagnosis in about 30% of cases with distant metastases. Liver metastases are widespread and associated with poor prognosis, especially in terms of response to immunotherapy. This prospective study will evaluate the efficacy of combined therapy involving sintilimab, fruquintinib, and radiotherapy in CRC with liver metastases. The primary objectives are to assess progression-free survival, overall survival, and treatment response rates. The rationale for this study stems from the intricate interplay between immunotherapy, targeted therapy, and radiotherapy in CRC management. Previous data suggest a negative correlation between liver metastases and immunotherapy efficacy, necessitating a comprehensive approach integrating multiple treatment modalities. Radiotherapy, particularly stereotactic body radiation therapy, has shown promise in controlling liver tumors and modulating the tumor microenvironment, potentially enhancing immunotherapy responses. This study aims to provide valuable insights into optimizing third-line and subsequent therapies for CRC with liver metastases by elucidating the efficacy and safety of this combined treatment approach.

Вмешательства

• Препарат Immunotherapy (Sintilimab)
  Sintilimab
• Препарат Targeted Therapy Agent (Fruquintinib)
  Fruquintinib
• Лучевая терапия Radiotherapy (SBRT and LDRT)
  SBRT and LDRT

Первичные конечные точки

• Progression-free survival (PFS) [Срок оценки: 1 year]

Вторичные конечные точки (4)

• Overall response rate (ORR) [Срок оценки: 1 year]
• Disease control rate (DCR) [Срок оценки: 1 year]
• Overall survival (OS) [Срок оценки: 3 year]
• The incidence and grade of adverse events [Срок оценки: 2 year]

Критерии участия

Критерии включения

• ECOG PS 0-2
• Histologically confirmed colorectal adenocarcinoma with liver metastases (8th edition AJCC)
• MSS/pMMR subtype
• Previously received standard first- and second-line systemic anti-tumor therapy
• At least one measurable lesion as defined by RECIST 1.1 criteria
• Access to tumor samples for biomarker assessment
• Expected survival of ≥3 months
• Normal function of major organ systems (within 14 days before enrollment)
• No systemic corticosteroid treatment within 7 days before treatment initiation, excluding physiological corticosteroid replacement therapy.
• Fertile males or females with the potential for pregnancy must use highly effective contraception methods during the trial.

Критерии исключения

• Patients diagnosed with malignancies other than colorectal cancer within 3 years prior to enrollment.
• Participating in an interventional clinical study or receiving other investigational drugs or treatments with study devices within the past 4 weeks before enrollment.
• Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs targeting another T cell co-stimulatory or co-inhibitory receptor (e.g., CTLA-4, OX-40, CD137), fruquintinib, etc.
• Received traditional Chinese medicine or immune-modulating drugs with anti-tumor indications within the past 2 weeks before enrollment (excluding local use for controlling pleural effusion).
• Experienced active autoimmune diseases requiring systemic therapy within the past 2 years before enrollment. Replacement therapy is not considered systemic therapy.
• Diagnosed with immune deficiency or received systemic corticosteroid therapy or any other form of immunosuppressive therapy within 7 days before the first dose of investigational treatment. After consultation with the sponsor, the use of physiological doses of corticosteroids may be approved.
• Received liver radiotherapy within the past 2 weeks before enrollment.
• Known presence of central nervous system metastases and/or carcinomatous meningitis.
• Received systemic corticosteroid therapy within 7 days before enrollment.

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

• Jinbo Yue — Цзинань

Публикации

• Ma Z, Zhu K, Shi F, Feng R, Jiang S, Dou X, Liu J, Niu Z, Yue J. Sintilimab plus fruquintinib with or without radiotherapy for third-line treatment of colorectal cancer with liver metastases: study protocol for a randomized controlled, multicenter phase II trial. Front Immunol. 2026 May 12;17:1622828. doi: 10.3389/fimmu.2026.1622828. eCollection 2026. PMID 42206059

Идентификаторы

NCT: NCT06356584 · SDZLEC2024-078-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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