Neoadjuvant Immunotherapy combined with Chemoradiotherapy VS. Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma(cStageII-III): Study Protocol For A Multi-center Prospective Randomized Clinical Trial

Abstract Background Neoadjuvant chemoradiotherapy (nCRT) combined with surgery has been suggested as the standard treatment for locally advanced ESCC. Meanwhile, CHECKMATE-577 has suggested that immunotherapy may be effective in controlling tumor recurrence and metastasis. According to PALACE-1, Neoadjuvant radiotherapy and chemotherapy combined with immunity may be more beneficial for patients. Therefore, it is meaningful to further study whether the combination of nCRT and immunotherapy has better effects in the treatment of ESCC. Methods NCT04973306 is designed as a multicenter, prospective, randomized, Phase II/Phase III clinical trial discussion, investigating the safety and efficacy of nCRT plus tumor immunotherapycompared with nCRT. A total of 476 patients with locally advanced resectable ESCC (stage cII-III) are randomly assigned to neoadjuvant immunotherapy combined with chemoradiotherapy (arm A) or nCRT (arm B) with a 1:1 allocation ratio. The primary endpoint of the first phase of the study was pCR. Overall survival assessed with a minimum follow-up of 36 months served as the study's main goal during the second phase (OS). Secondary outcomes are R0 resection rate, positive lymph node rate and response, number of lymph nodes cleared, tumor regression grade (TRG) of primary tumor, and disease-free survival (DFS) between the two groups Discussion This trial aims to study whether nCRT plus tumor immunotherapy yields superior benefits for curative treatment of ESCC and the survival. Trial registration number is NCT04973306.