Shanghai Wellcares Biopharmaceutical Co.,Ltd.

The goal of this study is planing to adopt intra-abdominal perfusion therapy of rmhTNF during radical colorectal cancer surgery to determine whether intra-abdominal therapy has an impact on postoperative intestinal function recovery, anastomotic leakage, postoperative bleeding, postoperative adhesion intestinal obstruction and other complications. On this basis, the effect of rmhTNF on postoperative peritoneal implantation metastasis and long-term survival was further studied. The main question it aims to answer is: To evaluate the safety and efficacy of rmhTNF in the treatment of peritoneal metastases in colorectal cancer. Participants will receive 1. Radical surgery: Surgical methods can be developed or endoscopic (including robotic surgery). Radical resection of colorectal cancer (corresponding resection of colon and rectum plus regional lymph node dissection, regional lymph node dissection including parenteral, intermediate and mesangial root lymph nodes) follows the principle of mesangectomy and tumorless operation. 2. Abdominal heat perfusion was performed twice: the first time, 5 million IUrmhTNF, dissolved in 30-50ml normal saline, was intraperitoneal heat perfusion into the surgical focus after the operation; the second time, rhatitrexed 2.5mg/m2 was injected into the abdominal cavity through thermoperfusion or drainage tube; 3. Postoperative systemic chemotherapy regimen: postoperative adjuvant chemotherapy should be started 3-4 weeks after surgery, and appropriately extended for patients with poor physique, but no later than 8 weeks after surgery. The chemotherapy regimen was determined by the clinician according to pathological stage, molecular typing, and risk factors, referring to the NCCN and CSCO guidelines.

主要有效性目的： 以无穿刺生存期（Puncture-Free Survival，PuFS）和客观缓解率（ORR）作为主要疗效指标，评价rmhTNF-NC+顺铂相较于顺铂单药腔内灌注治疗恶性胸、腹腔积液的有效性。 次要有效性目的： 基于以下次要疗效指标，评价rmhTNF-NC+顺铂相较于顺铂单药腔内灌注治疗恶性胸、腹腔积液的有效性： 1)6个月生存率（6m-OS）； 2)疾病控制率（DCR）； 3)总生存期（OS）； 4)患者报告结局（PRO）：生活质量评分（QLQ评分）相对于基线的变化。 安全性目的: 基于以下指标评估各治疗组的安全性： 1)不良事件的发生率和严重程度； 2)生命体征、体格检查、实验室检查（包括血常规、尿常规、血生化、凝血功能）以及心电图相对于基线的变化； 特别关注不良事件（AESI）发生率。