A Multicenter, Randomized Controlled Phase II Study of Short-Course Radiotherapy Followed by Sequential PD-1 Inhibitor and FOLFOX Chemotherapy Versus Long-Course Chemoradiotherapy for High-Risk Locally Advanced pMMR/MSS Lower Rectal Adenocarcinoma (STAR Trial)

Обзор

This study adopts a prospective randomized controlled design to evaluate the efficacy and safety of short-course radiotherapy followed by sequential PD-1 inhibitor and FOLFOX chemotherapy versus conventional regimens in high-risk locally advanced pMMR/MSS lower rectal adenocarcinoma, aiming to provide high-level evidence supporting a novel treatment paradigm.

Вмешательства

• Лучевая терапия Short-course Radiotherapy, SCRT
  The neoadjuvant treatment phase includes either SCRT followed by 6 cycles of FOLFOX chemotherapy combined with a PD-1 inhibitor, or LCRT concurrent with 6 cycles of FOLFOX chemotherapy. Surgery is performed 2-4 weeks after the last cycle of chemotherapy. If reassessment indicates cCR and N0, options include Total Mesorectal Excision (TME), local excision (LE), or watch and wait (W\&W); otherwise, TME is performed. Postoperative adjuvant chemotherapy follows the CAPOX regimen.
• Препарат Toripalimab
  The neoadjuvant treatment phase includes either SCRT followed by 6 cycles of FOLFOX chemotherapy combined with a PD-1 inhibitor, or LCRT concurrent with 6 cycles of FOLFOX chemotherapy. Surgery is performed 2-4 weeks after the last cycle of chemotherapy. If reassessment indicates cCR and N0, options include Total Mesorectal Excision (TME), local excision (LE), or watch and wait (W\&W); otherwise, TME is performed. Postoperative adjuvant chemotherapy follows the CAPOX regimen.

Первичные конечные точки

• CCR [Срок оценки: 3 years]

Вторичные конечные точки (7)

• 3-year RFS [Срок оценки: 3 years]
• 3-year DFS [Срок оценки: 3 years]
• 3-year OS [Срок оценки: 3 years]
• 3-year DMFS [Срок оценки: 3 years]
• R0 Resection Rate [Срок оценки: 3 years]
• MPR Rate [Срок оценки: 3 years]
• Treatment-Related Adverse Events / Treatment Toxicity [Срок оценки: 3 years]

Критерии участия

Критерии включения

• Before implementing any procedures related to the study protocol rather than routine clinical care, a signed and dated informed consent form must be obtained from the subject voluntarily, in accordance with regulatory requirements and institutional guidelines.
• Age 18-75 years.
• Histologically or cytologically confirmed pMMR/MSS rectal adenocarcinoma.
• The lower edge of the rectal tumor is located below the peritoneal reflection.
• Locally advanced disease with high-risk factors, meeting at least one of the following: cT4 / cN2 / EMVI+ / MRF+ / positive lateral lymph node.
• No clear evidence of distant metastasis prior to treatment.
• No prior anti-tumor therapy (radiotherapy, chemotherapy, targeted therapy, or immunotherapy).
• ECOG performance status 0-1 (Appendix 1).
• Peripheral blood counts and liver and renal function within the following ranges (tested within 15 days before treatment initiation):

• White blood cell count (WBC) ≥ 3.0 × 10⁹/L or absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;

• Hemoglobin (HGB) ≥ 80 g/L; ③ Platelet count (PLT) ≥ 100 × 10⁹/L; ④ Hepatic transaminases (AST/ALT) < 3.0 × upper limit of normal (ULN); ⑤ Total bilirubin (TBIL) < 1.5 × ULN; ⑥ Creatinine (CREAT) < 1.5 × ULN.
• No history of other concurrent malignancies; not pregnant or lactating; effective contraceptive methods should be used during the study period and for 6 months after the last dose.

Критерии исключения

• Patients with a history of severe drug allergy (including allergy to platinum agents, 5-FU, and 5-HT3 receptor antagonists).
• Patients who have participated in or are currently participating in another clinical trial within 4 weeks prior to enrollment.
• History of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4, or any other therapy specifically targeting T-cell co-stimulation or checkpoint pathways.
• Severe electrolyte abnormalities.
• Presence of gastrointestinal diseases such as active gastric or duodenal ulcer, ulcerative colitis, or unresected tumor with active bleeding; or other conditions that may cause gastrointestinal bleeding or perforation; or unhealed gastrointestinal perforation after surgical treatment.
• History of arterial thrombosis or deep vein thrombosis within 6 months; evidence of bleeding tendency or hemorrhagic history within 2 months; currently receiving high-dose anticoagulation therapy.
• Pregnant or lactating women, or women of childbearing potential with a positive pregnancy test prior to the first dose; or female participants and their partners who are unwilling to practice strict contraception during the study period.
• Presence of other concurrent or prior active malignancies (except for malignancies that have been curatively treated with no recurrence for more than 3 years, or carcinoma in situ that can be cured by adequate treatment).
• Severe electrocardiogram abnormalities, or active coronary artery disease, severe/unstable angina, newly diagnosed angina or myocardial infarction within 12 months prior to study entry, or congestive heart failure of NYHA Class II or higher.
• Patients with active infection (infection causing fever > 38°C).
• Patients with poorly controlled hypercalcemia, hypertension, or diabetes mellitus.
• Patients with severe pulmonary disease (interstitial pneumonia, pulmonary fibrosis, severe emphysema, etc.).
• Patients with mental disorders affecting clinical treatment or a history of central nervous system disease.
• Patients with severe complications (intestinal obstruction, renal insufficiency, hepatic insufficiency, cerebrovascular disorders, etc.).
• Presence of any unresolved toxicity of CTCAE Grade 2 or higher resulting from prior therapy (except for anemia, alopecia, and skin pigmentation).
• Any medical condition that is unstable or may affect patient safety and compliance with the study.
• Patients deemed by the investigator to be unsuitable for participation in this clinical trial.

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

Простое слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• The Sixth Affiliated Hospital of Sun Yat-sen University — Гуанчжоу

Идентификаторы

NCT: NCT07669220 · 2026ZSLYEC-285

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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