Department of Colorectal Surgery, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, Zhejiang, China.
Department of Colorectal Surgery, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, Zhejiang, China
BMJ Open. 2023 Mar 13;13(3):e069401. doi: 10.1136/bmjopen-2022-069401.
The NICHE trial showed remarkable results of neoadjuvant immunotherapy in colorectal cancer patients with mismatch repair (MMR) deficiency (dMMR). However, rectal cancer patients with dMMR accounted for only 10% of case. The therapeutic effect is unsatisfactory in MMR-proficient patients. Oxaliplatin has been demonstrated to induce immunogenic cell death (ICD), which may improve the therapeutic effect of programmed cell death 1 blockade; however, a maximum tolerated dose is required to induce ICD. Arterial embolisation chemotherapy provides drugs locally and can easily reach the maximum tolerated dose, which could be a significant method for delivering chemotherapeutic agents. Therefore, we designed a multicenter, prospective, single-arm, phase II study.
First, recruited patients will receive neoadjuvant arterial embolisation chemotherapy (NAEC) with oxaliplatin 85 mg/m and 3 mg/m. After 2 days, three cycles of immunotherapy with intravenous tislelizumab (200 mg/body, day 1) will be initiated at an interval of 3 weeks. From the second cycle of immunotherapy, the XELOX regimen will be added. 3 weeks after neoadjuvant therapy finished, the operation will be initiated. Neoadjuvant Arterial Embolization Chemotherapy Combined PD-1 Inhibitor for Locally Advanced Rectal Cancer (NECI) Study combined arterial embolisation chemotherapy, immunotherapy and systemic chemotherapy. Based on this combination therapy, the maximum tolerated dose could easily be reached, and ICD could be induced by oxaliplatin easily. To our knowledge, the NECI Study is the first multicenter, prospective, single-arm, phase II clinical trial to assess the efficacy and safety of NAEC combined with tislelizumab and systemic chemotherapy in locally advanced rectal cancer. This study is expected to provide a new neoadjuvant therapeutic regimen for locally advanced rectal cancer.
The Human Research Ethics Committee of the Fourth Affiliated Hospital of Zhejiang University School of Medicine approved this study protocol. The results will be published in peer-reviewed journals and presented at appropriate conferences.
NCT05420584.
NICHE 试验显示，错配修复（MMR）缺陷（dMMR）的结直肠癌患者新辅助免疫治疗的结果显著。然而，dMMR 的直肠患者仅占病例的 10%。在 MMR 功能正常的患者中，治疗效果并不令人满意。奥沙利铂已被证明能诱导免疫原性细胞死亡（ICD），这可能提高程序性细胞死亡 1 阻断的治疗效果；然而，需要达到最大耐受剂量才能诱导 ICD。动脉栓塞化疗局部提供药物，且易于达到最大耐受剂量，这可能是一种重要的化疗药物递送方法。因此，我们设计了一项多中心、前瞻性、单臂、Ⅱ期研究。
首先，招募的患者将接受奥沙利铂 85mg/m 和 3mg/m 的新辅助动脉栓塞化疗（NAEC）。2 天后，每 3 周静脉注射替雷利珠单抗（200mg/体，第 1 天）开始进行 3 个周期的免疫治疗。从第 2 个免疫治疗周期开始，加入 XELOX 方案。新辅助治疗结束后 3 周，开始手术。新辅助动脉栓塞化疗联合 PD-1 抑制剂治疗局部晚期直肠癌（NECI）研究联合了动脉栓塞化疗、免疫治疗和全身化疗。基于这种联合治疗，很容易达到最大耐受剂量，且奥沙利铂很容易诱导 ICD。据我们所知，NECI 研究是首个评估局部晚期直肠癌中 NAEC 联合替雷利珠单抗和全身化疗的疗效和安全性的多中心、前瞻性、单臂、Ⅱ期临床试验。该研究有望为局部晚期直肠癌提供新的新辅助治疗方案。
浙江大学医学院附属第四医院的人类研究伦理委员会批准了本研究方案。研究结果将发表在同行评议的期刊上，并在适当的会议上展示。
NCT05420584。
