Total Neoadjuvant Treatment With Short-course Radiotherapy Versus Long-course Radiotherapy Followed by PD-L1 Inhibitor Plus Capecitabine-Oxaliplatin in Patients With Locally Advanced Rectal Cancer: a Multi-centres, Open-label, Phase 2, Randomized Controlled Trial
This is a multicenter, cohort, prospective study to evaluate the efficacy and safety of Adebrelimab combined with radiotherapy and chemotherapy as preoperative neoadjuvant therapy for patients with locally advanced rectal cancer. In the study, all subjects who meet the inclusion criteria will enter the short-term radiotherapy queue and the long-term radiotherapy queue at the ratio of 1:1. The short-term radiotherapy queue plans to receive Adebrelimab combined with short-term radiotherapy (5\*5Gy) and Capox chemotherapy as neoadjuvant therapy. The long-term radiotherapy queue plans to receive Adebrelimab combined with long-term radiotherapy (1.8gy × 25-28 times) and capox chemotherapy as neoadjuvant therapy. The TME surgery will be performed 2-3 weeks after the last neoadjuvant therapy is completed. If the surgery cannot be performed within the time window specified in the plan (such as delayed adverse reactions, etc.), the researcher will conduct the surgery according to the patients' requirements.The actual clinical conditions of the subjects were comprehensively considered.
• 1\. sign written informed consent before implementing any test related process;
• 2\. Patients diagnosed as rectal adenocarcinoma by primary biopsy and histopathological examination;
• 3\. patients with CT stage ≥ T3 or CN stage N1+, M0 or EMVI (+) or MRF (+) or suspected lateral lymph node metastasis (\>5mm) who are judged by imaging and colonoscopy to be operable and need neoadjuvant therapy.
• 4\. according to imaging and colonoscopy, the main body of the tumor was located ≤ 10cm from the anal edge;
• 5\. patients with tumor mismatch repair/microsatellite instability (MMR/MSI) status as MSS;
• 6\. according to the criteria for evaluating the efficacy of solid tumors (RECIST version 1.1), at least one lesion can be measured by imaging;
• 7\. the patient has not received any anti-tumor treatment in the past, including but not limited to surgery, radiotherapy, chemotherapy, immunotherapy, targeted therapy, etc;
• 8\. ECoG score: 0-1;
• 9\. sufficient organ function, the subject shall meet the following laboratory indicators:
‣ The absolute value of neutrophils (ANC) ≥ 1.5x109/l without granulocyte colony stimulating factor in the past 14 days.
⁃ Platelets ≥ 100 × 109/l without blood transfusion in recent 14 days.
⁃ Hemoglobin\>9g/dl without blood transfusion or use of erythropoietin in recent 14 days;
⁃ Total bilirubin ≤ 1.5 × upper limit of normal value (ULN);
⁃ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in ≤ 2.5 × ULN
⁃ Serum creatinine ≤ 1.5 × ULN and creatinine clearance rate (calculated by Cockcroft Gault formula) ≥ 60 ml/min;
⁃ Good coagulation function was defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 times ULN;
⁃ Normal thyroid function is defined as thyroid stimulating hormone (TSH) within the normal range. If the baseline TSH is beyond the normal range, subjects with total T3 (or FT3) and FT4 within the normal range can also be enrolled;
⁃ Myocardial enzyme spectrum is within the normal range (for example, simple laboratory abnormalities that are not clinically significant according to the comprehensive judgment of the researcher are also allowed to be included in the group)
• 10\. female subjects of childbearing age should receive urine or serum pregnancy test within 3 days before receiving the first study drug administration (the first day of the first cycle) and the result is negative. If the result of urine pregnancy test cannot be confirmed as negative, blood pregnancy test is required. Women of non reproductive age were defined as having been postmenopausal for at least 1 year, or having undergone surgical sterilization or hysterectomy; If there is a risk of pregnancy, all subjects (male or female) need to take contraceptive measures with an annual failure rate of less than 1% during the whole treatment period until 120 days after the last study drug administration (or 180 days after the last chemotherapy drug administration).