Neoadjuvant ChemoRadiotherapy Followed by Immunotherapy and Surgery for Resectable Esophageal Squamous Cell Carcinoma（CRIS-2 Trial）
NCT Number: NCT06509568
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Esophageal Squamous Cell Carcinoma
Interventions: RADIATION: Neoadjuvant chemoradiotherapy followed by immunotherapy|DRUG: Neoadjuvant chemoimmunotherapy
Sponsor: Zhejiang Cancer Hospital
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 92
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-01
Completion Date: 2026-08-01
Locations: Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China

Summary:
Based on our previous single-arm Phase Ib study (CRIS trial, NCT06303583), we observed that neoadjuvant chemoradiotherapy followed by immunotherapy (nCRIT) significantly increased the pathological complete response (pCR) rate, achieving approximately 60% in locally advanced esophageal squamous cell carcinoma(ESCC). We plan to initiate a multicenter, prospective, randomized phase II trial designed to compare the efficacy and safety of neoadjuvant chemoimmunotherapy (nCIT) versus neoadjuvant chemoradiotherapy followed by immunotherapy (nCRIT) in treating esophageal squamous cell carcinoma. The primary study population includes patients with operable or potentially operable thoracic ESCC classified as cT3-4aN0 or T2-4aN+ based on endoscopy, enhanced chest and abdominal CT, and whole-body PET scans. Eligible participants are aged 18-75 years with an ECOG performance status of 0-1. Qualified patients will be randomly assigned in a 1:1 ratio to either the nCRIT group or the nCIT group.

Patients in the nCRIT group will receive neoadjuvant concurrent chemoradiotherapy: radiation therapy will be administered using IMRT or VMAT with involved-field irradiation at a dose of PTV 41.4 Gy/23 fractions/31 days. Chemotherapy will consist of weekly administration of paclitaxel (albumin-bound) 50 mg/m² and carboplatin (AUC=2) for five weeks, given on the days of radiotherapy. Patients who do not progress on CT and meet immunotherapy criteria will receive fixed-dose toripalimab (200 mg IV) on days 8 and 29 after chemoradiotherapy, followed by minimally invasive esophagectomy four weeks after completing immunotherapy.

Patients in the nCIT group will receive two cycles of TC chemotherapy combined with immunotherapy, specifically paclitaxel (albumin-bound) 100 mg/m² on days 1, 8, 15 or 260mg/m² d1, carboplatin (AUC=5) on days 1, and toripalimab (200 mg) on days 1. Minimally invasive esophagectomy will be performed 4-6 weeks after completing chemotherapy, and adjuvant immunotherapy is recommended for one year after surgery.

The primary endpoint of the study is the pathological complete response (pCR). Secondary endpoints include treatment safety, CT imaging response rate, R0 resection rate, major pathological response (MPR), 2-year event-free survival (EFS), 2-year overall survival (OS) in the intention-to-treat (ITT) population, and analysis of treatment failure reasons.

Primary Outcome Measures: pCR, Pathologic complete response (pCR) was defined as the absence of cancer cells in both the esophagus and lymph nodes following neoadjuvant chemoradiotherapy, 1 months after surgery
Secondary Outcome Measures: R0 resection rate, R0 resection rate refers to the proportion of patients who undergo a surgical procedure to remove a tumor and achieve a complete resection with no residual microscopic disease., 1 months after surgery|MPR, Major pathological response (MPR) is a measure of neoadjuvant immunotherapy efficacy. It is defined as having no more than 10% residual viable tumor cells by routine hematoxylin and eosin (H\&E) staining after therapy., 1 months after surgery|2-year EFS, Event-Free Survival (EFS) refers to the length of time after the treatment starts during which a patient remains free from certain negative events, such as disease progression, recurrence, or death from any cause., 2 years after randomization|2-year OS, Time from randomization to any death, 2 years after randomization|Adverse Events, any undesirable experiences or side effects that occur in a patient during the trial, 2 years after randomization|HRQoL, Health-Related Quality of Life (HRQoL) refers to a patient's overall well-being, encompassing physical, mental, and social aspects of health as they are affected by a medical condition or its treatment., 2 years after randomization