PMID- 36910109 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230314 IS - 2072-1439 (Print) IS - 2077-6624 (Electronic) IS - 2072-1439 (Linking) VI - 15 IP - 2 DP - 2023 Feb 28 TI - Neoadjuvant therapy with immunoagent (nivolumab) or placebo plus chemotherapy followed by surgery and adjuvant treatment in subjects with resectable esophageal squamous cell carcinoma: study protocol of a randomized, multicenter, double blind, phase II trial (NATION-2203 trial). PG - 718-730 LID - 10.21037/jtd-22-1789 [doi] AB - BACKGROUND: Neoadjuvant chemotherapy (nCT) has been the recommended treatment for locally advanced esophageal squamous cell carcinoma (ESCC). The addition of programmed cell death protein 1 (PD-1) inhibitor to nCT may improve oncologic outcome and survival. However, high-level evidence of neoadjuvant immunotherapy (nIT) combined with nCT in locally advanced resectable ESCC patients are still lacking. Hence, we describe this randomized controlled trial in order to assess the efficacy and safety of neoadjuvant nivolumab in combination with chemotherapy for locally advanced (stage II-III) ESCC patients. METHODS: This prospective, randomized, multicenter phase II trial aims to enroll 90 locally advanced (stage II-III) ESCC patients who will undergo nivolumab or placebo plus chemotherapy followed by surgery. Patients will be 2:1 randomized to nivolumab/chemo and placebo/chemo group by method of stratified randomization. In both arms, patients who have not achieved complete pathological complete response (pCR) will be administered with adjuvant nivolumab for up to 1 year. The primary endpoint is pCR rate and secondary endpoints include event-free survival (EFS), R0 resection rate, and adverse events (AEs). The safety will be evaluated by AEs, grading by Common Terminology Criteria for Adverse Events (CTCAE) 5.0 classifications. The double-blind will be maintained between subjects and investigators until the final unblinding process. DISCUSSION: This protocol has been reviewed and approved by the Ethics Committee of Zhongshan Hospital (B2022-004R). This is the first prospective, multicenter, randomized controlled trial to compare the combination of immunotherapy and chemotherapy with standard chemotherapy in neoadjuvant treatment for ESCC, also to explore whether adjuvant immunotherapy offers additional benefit in non-pCR patients after nCT with/without immunotherapy and R0 resection. We hypothesize that the pCR rate, R0 resection rate, EFS and OS of the study group (nivolumab/chemo) is significantly better than those of control group. REGISTRATION: ClinicalTrial.gov: NCT05213312. CI - 2023 Journal of Thoracic Disease. All rights reserved. FAU - Yin, Jun AU - Yin J AD - Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Lin, Siyun AU - Lin S AD - Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Fang, Yong AU - Fang Y AD - Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Jiao, Heng AU - Jiao H AD - Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Chen, Zongwei AU - Chen Z AD - Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Tang, Han AU - Tang H AD - Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Gu, Jianmin AU - Gu J AD - Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Zhang, Shaoyuan AU - Zhang S AD - Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Sun, Linyi AU - Sun L AD - Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. FAU - Li, Yin AU - Li Y AD - Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. FAU - Han, Yongtao AU - Han Y AD - Department of Thoracic Surgery, Sichuan Cancer Hospital & Research Institute, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China. FAU - Chen, Qixun AU - Chen Q AD - Department of Thoracic Oncological Surgery, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, China. FAU - Chen, Haiquan AU - Chen H AD - Department of Thoracic Surgery, Fudan University Shanghai Cancer Center & Institute of Thoracic Oncology & State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, China. FAU - Li, Zhigang AU - Li Z AD - Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Tan, Lijie AU - Tan L AD - Department of Thoracic Surgery, Zhongshan Hospital of Fudan University, Shanghai, China. AD - Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, China. LA - eng SI - ClinicalTrials.gov/NCT05213312 PT - Journal Article DEP - 20230208 PL - China TA - J Thorac Dis JT - Journal of thoracic disease JID - 101533916 PMC - PMC9992557 OTO - NOTNLM OT - Esophageal squamous cell carcinoma (ESCC) OT - adjuvant OT - chemotherapy OT - neoadjuvant OT - nivolumab COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-22-1789/coif). HC serves as an unpaid editorial board member of Journal of Thoracic Disease from October 2022 to September 2024. LT reports that the study was funded by Bristol-Myers Squibb (CA209-6KP). The other authors have no conflicts of interest to declare. EDAT- 2023/03/14 06:00 MHDA- 2023/03/14 06:01 PMCR- 2023/02/28 CRDT- 2023/03/13 04:08 PHST- 2022/12/11 00:00 [received] PHST- 2023/01/10 00:00 [accepted] PHST- 2023/03/13 04:08 [entrez] PHST- 2023/03/14 06:00 [pubmed] PHST- 2023/03/14 06:01 [medline] PHST- 2023/02/28 00:00 [pmc-release] AID - jtd-15-02-718 [pii] AID - 10.21037/jtd-22-1789 [doi] PST - ppublish SO - J Thorac Dis. 2023 Feb 28;15(2):718-730. doi: 10.21037/jtd-22-1789. Epub 2023 Feb 8.