SCRT Followed by CAPOX + Bev ± PD-1 Inhibitor for TNT in LARC

Официальное название

Short-Course Radiotherapy Combined With CAPOX and Bevacizumab, With or Without PD-1 Inhibitors, as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

Обзор

This study aims to evaluate the efficacy and safety of short-course radiotherapy combined with CAPOX plus bevacizumab with or without a PD-1 inhibitor in patients with locally advanced rectal cancer (LARC). The hypothesis is that the addition of immunotherapy (PD-1 inhibitor) can significantly improve the complete response (CR) rate and enhance local control while reducing the incidence of distant metastasis. This study will compare the effects of sequential chemoradiotherapy and targeted therapy with or without immunotherapy following short-course radiotherapy, aiming to explore the optimal regimen for total neoadjuvant therapy.

Вмешательства

• Препарат PD-1 inhibitor based immunotherapy
  Short-course radiotherapy (25Gy/5Fx) followed by 4 cycles of CAPOX regimen (Oxaliplatin 130mg/m² IV infusion, Capecitabine 1000mg/m² orally for 14 days, Q3w) combined with Bevacizumab (7.5mg/kg IV infusion, D1, Q3w) + PD-1 inhibitor (Toripalimab 240mg IV infusion, D1, Q3w).

Первичные конечные точки

• Complete Response rate [Срок оценки: 2 weeks after the surgery]

Вторичные конечные точки (7)

• Disease-Free Survival (DFS) [Срок оценки: from enrollment to the end of follow-up at 48 months]
• Distant Metastasis Rate [Срок оценки: from enrollment to the end of follow-up at 48 months]
• Local Recurrence Rate [Срок оценки: from enrollment to the end of follow-up at 48 months]
• Overall Survival (OS) [Срок оценки: from enrollment to the end of follow-up at 48 months]
• Pathological Stage [Срок оценки: 2 weeks after the surgery]
• Tumor Regression Grade(TRG) [Срок оценки: 2 weeks after the surgery]
• Sphincter Preservation Rate [Срок оценки: 2 weeks after the surgery]

Критерии участия

Критерии включения

• Histopathologically confirmed rectal adenocarcinoma with no prior antitumor therapy.
• Exclusion of patients with BRAF mutations or MSI-H status, as determined by pre-enrollment genetic testing including RAS, BRAF, and MSI analysis. RAS mutation status is permitted regardless.
• Absence of severe intestinal obstruction symptoms and no evidence of distant metastasis confirmed by imaging examinations such as CT, MRI, or PET/CT.
• Confirmation as locally advanced rectal cancer by rectal MRI, meeting one or more of the following criteria: T3c-d or T4, N2, EMVI(+), MRF(+), lateral lymph node metastasis; or patients with low-lying rectal cancer (≤5 cm from the anal verge) unsuitable for sphincter-preserving surgery prior to neoadjuvant therapy.
• Age 18 to 75 years.
• ECOG Performance Status of 0 to 1, without severe comorbid medical conditions.
• Adequate organ function:

Hematopoietic: Hemoglobin ≥90 g/L, Platelets ≥80 × 10\^9/L, Absolute Neutrophil Count ≥1.5 × 10\^9/L.

Hepatic: ALT and AST < 2.5 × ULN. Renal: Serum Creatinine < 1.5 × ULN.

• Provision of signed and dated written informed consent.

Критерии исключения

• Patients found to have BRAF mutations or MSI-H status.
• Patients who have previously received chemotherapy, radiotherapy, immunotherapy, targeted therapy, or surgical resection for colorectal cancer prior to enrollment.
• History or presence of another malignancy (except for early-stage basal cell carcinoma or carcinoma in situ of the cervix) within the past 3 years, with the disease not under control.
• Patients who are pregnant (confirmed by serum or urine β-HCG test) or breastfeeding.
• Patients with severe cardiac, hepatic, renal, neurological, or psychiatric diseases.
• Patients with active infections.
• Poor overall health status, with an ECOG performance status ≥2.
• Patients who have undergone organ transplantation requiring immunosuppressive therapy, or those requiring long-term corticosteroid treatment for autoimmune diseases.
• Patients with comorbid conditions that, in the investigator's judgment, seriously endanger the patient's safety or affect the completion of the study.
• Known hypersensitivity to any of the study drugs.

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

• Ruijin Hospital, Shanghai Jiaotong University School of Medicine — Шанхай

Идентификаторы

NCT: NCT07198165 · TRAINER-2

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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