CAPOX and PD-1 Antibody Combined With or Without Radiotherapy for MSS Locally Advanced Rectal Cancer

Официальное название

A Prospective Randomized Phase II Trial of CAPOX and PD-1 Antibody Combined With or Without Radiotherapy for Microsatellite Stable Locally Advanced Rectal Cancer (TORCH-iTNT)

Обзор

TORCH-iTNT is a prospective, multicentre, randomized phase II trial. 198 LARC (T3-4/N+M0, distance from anal verge ≤12cm) patients will be treated with total neoadjuvant therapy (TNT) and assigned to Group A and Group B (1:1). Group A receives 6 cycles of Toripalimab combined with CAPOX (ToriCAPOX). Group B receives SCRT (25Gy/5Fx) followed by 6 cycles of ToriCAPOX. TME surgery is scheduled after TNT while a watch and wait (W\&W) option can be applied to patients achieving clinical complete response (cCR). The primary endpoint is complete response (CR, pathological complete response \[pCR\] plus cCR) rate. The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, organ or anal preservation rate, 3-year DFS rate, etc.

Вмешательства

• Препарат PD-1 inhibitor
  PD-1 inhibitor (Toripalimab): 240mg d1 q3w
• Препарат Capecitabine
  Capecitabine: 1000mg/m2 bid d1-14 q3w
• Лучевая терапия Short-course radiotherapy
  Short-course radiotherapy: 25Gy/5Fx
• Препарат Oxaliplatin
  Oxaliplatin 130mg/m2 d1 q3w

Первичные конечные точки

• Complete response (CR) rate [Срок оценки: 1 month after the surgery or the decision of W&W]

Вторичные конечные точки (7)

• Grade 3-4 adverse effects rate [Срок оценки: From date of randomization until 3 months after the completion neoadjuvant therapy]
• 3 year organ or anal preservation rate [Срок оценки: From date of randomization until the resection of rectum or anus, assessed up to 36 months.]
• 3 year disease free survival rate [Срок оценки: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months.]
• 3 year local recurrence free survival rate [Срок оценки: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months.]
• 3 year distant metastasis free survival rate [Срок оценки: From date of randomization until the date of first documented distant metastasis, assessed up to 36 months.]
• 3 year overall survival rate [Срок оценки: From date of randomization until the date of death from any cause, assessed up to 36 months.]
• Rate of surgical complications [Срок оценки: The surgical complications were assessed within 3 months after the surgery.]

Критерии участия

Критерии включения

• Age 18-70 years old, female and male;
• Pathological confirmed adenocarcinoma;
• The distance from anal verge ≤ 10 cm;
• MSI/MMR status: MSS/pMMR;
• Clinical stage T3-4 and/or N+, without distance metastases;
• At least one of the following factors is present: distance from the anus ≤5 cm, cT4, cN2, positive cMRF, positive cEMVI, or positive lateral lymph nodes;
• KPS ≥ 70;
• No radiotherapy, chemotherapy, immunotherapy, or any other anti-tumor therapy had been administered prior to enrollment;
• Baseline blood and biochemical indicators meet the following criteria: neutrophils ≥ 1.5 × 10\^9/L, Hb ≥ 90 g/L, PLT ≥ 100 × 10\^9/L, ALT/ AST ≤ 2.5 ULN, Cr ≤ 1 ULN;
• With good compliance and signed the consent form.

Критерии исключения

• Pregnancy or breast-feeding women;
• Known history of other malignancies within 5 years;
• Known history of severe neurological or mental illness (such as schizophrenia, dementia or epilepsy);
• Current severe cardiac disease (cardiac dysfunction and arrhythmia), renal dysfunction and liver dysfunction;
• Acute cardiac infarction or cerebral ischemic stroke occurred within 6 months before recruitment;
• Uncontrolled infection which needs systemic therapy;
• Active autoimmune disease or immunodeficiencies, known history of organ transplantation or systematic use of immunosuppressive agents;
• Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1 to 2 antibody positive), active syphilis infection, active pulmonary tuberculosis infection;
• Allergic to any component of the therapy.

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: NCT06281405 · FDRT-2023-290-3409

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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