卡瑞利珠单抗联合放疗新辅助治疗局部晚期食管鳞癌的安全性和有效性的前瞻性单臂 II 期临床研究方案。

Safety and efficacy of camrelizumab combined with radiotherapy as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a prospective single-arm phase II clinical trial protocol.

机构信息

Department of Thoracic Surgery, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, Fujian, China.

Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, Fujian, China.

出版信息

Trials. 2023 Aug 25;24(1):554. doi: 10.1186/s13063-023-07534-3.

DOI:10.1186/s13063-023-07534-3

PMID:37626367

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10463929/

Abstract

BACKGROUND

Neoadjuvant chemoradiotherapy followed by esophagectomy is the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 30% of patients still develop distant metastases and have a high incidence of treatment-related adverse events. Immunotherapy, as a new modality for anti-cancer treatment, has shown promising clinical benefits for patients with ESCC. The synergistic effects of immunotherapy and radiotherapy make their combination promising as neoadjuvant treatment for locally advanced ESCC.

METHODS

All participants who meet the inclusion criteria will be enrolled after signing the informed consent form. Patients with thoracic segment esophageal cancer with clinical stage T2-3 N0 M0 or T2-3 N + M0 will be included. A total of 25 patients are to be recruited for the study. Twelve patients will be recruited in phase I, with at least two achieving major pathological response (MPR) before entering phase II. They will be treated with radical surgery within 4-8 weeks after the completion of two cycles of neoadjuvant radiotherapy in combination with camrelizumab according to the study schedule. The primary endpoint is the major pathological remission rate of all per-protocol patients. The secondary endpoints are the R0 resection rate, pathological complete remission rate, and adverse events. The interim analysis will be conducted after 12 patients have been enrolled. The trials will be terminated when more than two treatment-related deaths occur or fewer than five patients have major pathological remission.

DISCUSSION

We designed this prospective single-arm phase II clinical study to evaluate the combination of camrelizumab and standard radiotherapy as preoperative neoadjuvant therapy for patients with resectable ESCC as part of the quest for better treatment options for patients with locally advanced ESCC.

TRIAL REGISTRATION

This trial protocol has been registered on the NIH Clinical Trials database ( www.

CLINICALTRIALS

gov/ , NCT05176002. Registered on 2022/01/04). The posted information will be updated as needed to reflect protocol amendments and study progress.

摘要

背景

新辅助放化疗后行食管切除术是局部晚期食管鳞状细胞癌（ESCC）的标准治疗方法。然而，约 30%的患者仍会发生远处转移，且治疗相关不良事件发生率较高。免疫治疗作为一种新的抗癌治疗方式，为 ESCC 患者带来了有前景的临床获益。免疫治疗与放疗的协同作用使它们联合应用于局部晚期 ESCC 的新辅助治疗具有广阔前景。

方法

所有符合纳入标准的参与者在签署知情同意书后将被纳入研究。纳入标准为临床分期为 T2-3N0M0 或 T2-3N+M0 的胸段食管癌患者。本研究计划招募 25 例患者。其中 12 例患者将在 I 期入组，至少有 2 例患者在进入 II 期前达到主要病理缓解（MPR）。按照研究方案，在完成两周期新辅助放化疗联合卡瑞利珠单抗治疗后 4-8 周内行根治性手术。主要终点为所有符合方案患者的主要病理缓解率。次要终点为 R0 切除率、病理完全缓解率和不良事件。在 12 例患者入组后将进行中期分析。当出现 2 例以上与治疗相关的死亡或少于 5 例患者达到主要病理缓解时，试验将终止。