This is a prospective, single-center, randomized controlled, phase II clinical trial. The study aims to enroll 48 patients with resectable, locally advanced gastroesophageal junction adenocarcinoma who have not received any treatment. After obtaining informed consent and meeting the inclusion/exclusion criteria, patients were randomly assigned preoperatively in a 1:2 ratio: Arm A. Radiochemoimmunotherapy group (n=16): 3 cycles of serplulimab combined with modified SOX (mSOX) combined with radiotherapy, as details: Cycle 1: Serplulimab: 300 mg, i.v., D1 Oxaliplatin: 130 mg/m², i.v., D1 S-1 (Tegafur/Gimeracil/Oteracil): Oral administration: 40 mg twice daily for BSA \< 1.25 m²; 50 mg twice daily for BSA 1.25 to \<1.5 m²; 60 mg twice daily for BSA ≥ 1.5 m². Administered from D1 to D14, followed by a rest period from D15 to D21. This cycle lasts 21 days. Cycle 2: Serplulimab: 300 mg, i.v., D1 S-1: Oral administration: 40 mg twice daily from D1 to D14 of the treatment cycle. Radiotherapy: Commences between D2 and D5 after the start of Cycle 2. The clinical target volume (CTV) is defined as the endoscopically marked tumor boundary and adjacent metastatic lymph nodes plus a 5-10 mm margin. The planning target volume (PTV) is generated by adding an additional 5-10 mm margin to the CTV. The planned dose to the PTV is 44 Gy administered in 22 fractions, with 5 fractions per week. This is followed by a 7-day rest interval. This cycle lasts 33 days. Cycle 3: Serplulimab: 300 mg, i.v., D1 Oxaliplatin: 130 mg/m², i.v., D1 Fluorouracil Injection: Administered as a 400 mg/m² intravenous bolus on day 1, followed immediately by a continuous intravenous infusion of 2400-3000 mg/m² over 46 hours. This is followed by a 7-day rest period. This cycle lasts 9 days. Arm B: Immunomodulation group (n=32): 3 cycles of serplulimab combined with mSOX combined with radiotherapy (as described above) and 9 weeks of neoadjuvant thymosin; After neoadjuvant therapy, the efficacy of the therapy and the feasibility of radical D2 resection are assessed through imaging examinations. Efficacy evaluation is performed within 2 weeks of the completion of neoadjuvant therapy, and radical gastrectomy is performed within 4-6 weeks. Postoperative treatment is determined jointly by the clinician and the patient based on actual clinical practice. The primary endpoint is complete pathological response (pCR) rate, defined as the proportion of subjects who have no residual surviving tumor cells under microscopic examination and are negative for lymph nodes. Safety assessment: Safety assessments are performed after each cycle of neoadjuvant therapy and 30 days postoperatively. Event follow-up: Follow-up events are then conducted every 3 months for the first year postoperatively, and every 6 months for 1-2 years, up to 2 years postoperatively.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
48
3 cycles of serplulimab combined with mSOX combined with radiotherapy.
3 cycles of serplulimab combined with mSOX combined with radiotherapy and 9 weeks of thymosin-based neoadjuvant therapy;
First Affiliated Hospital of Nanjing Medical Unviersity
Nanjing, Jiangsu, China
RECRUITINGComplete pathological response (pCR) rate
Defined as the proportion of subjects who have no residual surviving tumor cells under microscopic examination and are negative for lymph nodes
Time frame: from surgery to 1 month after surgery
Major Pathological Response (MPR)
For patients with surgically resectable gastric cancer after neoadjuvant therapy, the proportion of patients with less than 10% residual tumor cells in the primary site.
Time frame: from preoperative to 10 days postoperative
Tumor Regression Grade (TRG)
It is intended to grade the pathological response of tumor after neoadjuvant therapy and generally divide the grade mainly according to the proportion of fibrosis and residual tumor in the tumor. In this study, Becker criteria are used to grade TGR as follows: TRG1a (no residual tumor), equivalent to pCR; TRG1b (\< 10% residual tumor); TRG2 (10% to 50% residual tumor); and TRG3 (\> 50% residual tumor).
Time frame: from preoperative to 10 days postoperative
Objective Response Rate (ORR)
It refers to the proportion of patients whose tumor shrinks to a certain extent and remains for a certain period of time, including CR (Complete Response) and PR (Partial Response) cases. Objective tumor response will be assessed using Response Evaluation Criteria in Solid Tumors (RECIST 1.1 criteria).
Time frame: before surgery
Disease-free Survival (DFS)
Disease-free survival refers to the time from the start of randomization to disease recurrence or death due to disease progression. DFS will be defined as the last date the patient is last confirmed to be disease-free survival if the patient does not experience disease progression during the study.
Time frame: 2 years after surgery
R0 resection rate
R0 resection rate refers to the proportion of patients who complete R0 resection in surgically resectable patients after neoadjuvant therapy.
Time frame: from preoperative to 10 days postoperative
treatment-related adverse event (TRAE)
incidence of treatment-related adverse event
Time frame: from the start of neoadjuvant therapy to 30 days after surgery
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