Short-Course Radiotherapy Combined With CAPOX and Bevacizumab, With or Without PD-1 Inhibitors, as Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Complete Response rate
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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 ≥
- •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.
研究组 & 干预措施
Intervention group
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). Following completion of total neoadjuvant therapy, the treatment strategy (watch-and-wait or surgical resection) will be selected based on tumor response. The decision regarding adjuvant chemotherapy will be determined according to postoperative pathological findings.
干预措施: PD-1 inhibitor based immunotherapy (Drug)
结局指标
主要结局
Complete Response rate
时间窗: 2 weeks after the surgery
Measurement Methods: Chi-square test, Fisher's exact test, multivariate regression analysis (Cox regression model). Description: For pCR and cCR, chi-square test or Fisher's exact test was used to compare differences between the two groups. Multivariate regression analysis (Cox regression model) was employed to assess the relationship between the intervention and the CR rate.
次要结局
- Disease-Free Survival (DFS)(from enrollment to the end of follow-up at 48 months)
- Distant Metastasis Rate(from enrollment to the end of follow-up at 48 months)
- Local Recurrence Rate(from enrollment to the end of follow-up at 48 months)
- Overall Survival (OS)(from enrollment to the end of follow-up at 48 months)
- Pathological Stage(2 weeks after the surgery)
- Tumor Regression Grade(TRG)(2 weeks after the surgery)
- Sphincter Preservation Rate(2 weeks after the surgery)