Short-Course Radiotherapy Followed by Liposomal Irinotecan, Oxaliplatin, Capecitabine, and Sintilimab as Total Neoadjuvant Therapy in High-Risk Locally Advanced Rectal Cancer: A Single-Arm, Single-Center, Exploratory Study
This is a single-center, exploratory clinical study for patients with newly diagnosed, high-risk, locally advanced rectal cancer. The study aims to evaluate the effectiveness and safety of a comprehensive pre-surgery (neoadjuvant) treatment strategy. All participants will receive a short course of radiation therapy (25 Gy in 5 fractions) over one week. This will be followed by a combination of chemotherapy (Liposomal Irinotecan, Oxaliplatin, and Capecitabine) and immunotherapy (Sintilimab). This combined treatment is administered for six cycles. For patients who achieve a complete response, the option to avoid immediate surgery and enter a close monitoring program (Watch and Wait) will be considered.
• Voluntary Participation: Subjects voluntarily participate in the study, sign the informed consent form, and have good compliance.
• Age and Gender: Age between 18 and 75 years, any gender.
• Pathological Diagnosis: Histologically or cytologically confirmed rectal adenocarcinoma; confirmed mismatch repair proficient (pMMR) or microsatellite stable (MSS) by genetic testing or immunohistochemistry.
• Disease Stage: Assessed as high-risk, mid-low (distance from the anal verge ≤10 cm) locally advanced rectal cancer by colonoscopy, digital rectal exam, or MRI. High-risk definition: Meeting at least one of the following: cT4, extramural vascular invasion (EMVI), tumor deposits, involvement of the mesorectal fascia or intersphincteric plane.
• Prior Treatment: No prior anti-tumor therapy for this rectal cancer (including surgery, radiotherapy, chemotherapy, immunotherapy, or targeted therapy).
• Measurable Lesion: At least one measurable lesion according to RECIST v1.1 criteria.
• Tumor Tissue Sample: Must provide tumor tissue samples for biomarker analysis.
• Adequate Organ Function (within 7 days before the first dose): 1) Hematological: Hemoglobin ≥90 g/L; White Blood Cell count ≥3.0 x 10⁹/L; Absolute Neutrophil Count ≥1.5 x 10⁹/L; Platelets ≥100 x 10⁹/L. 2) Hepatic: Total Bilirubin \<1.5 x ULN; AST and ALT ≤2.5 x ULN; Albumin ≥30 g/L. 3) Renal: Serum Creatinine ≤1.5 x ULN OR Creatinine Clearance ≥50 mL/min. 4) Coagulation: INR ≤1.5 x ULN (or ≤3 x ULN if on stable anticoagulant therapy); PTT or aPTT ≤1.5 x ULN (or ≤3 x ULN if on stable anticoagulant therapy).
• Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Life Expectancy: Expected survival time ≥3 months.
• Good organ function.
• Contraception: Subjects of childbearing potential must agree to use effective contraception during the treatment period and for 6 months after the last dose.