This study aims to compare the efficacy and safety of neoadjuvant apatinib combined with sintilimab and perioperative SOX chemotherapy versus neoadjuvant sintilimab combined with perioperative SOX chemotherapy in locally advanced intestinal-type gastric cancer/gastroesophageal junction adenocarcinoma. The primary questions include: 1. Whether the complete remission rate (pCR) of the apatinib combined with sintilimab and SOX regimen is higher than that of the sintilimab combined with SOX regimen. 2. The safety of the apatinib combined with sintilimab and SOX regimen. Participants will be divided into: 1. Experimental Group: Participants will receive an intravenous injection of sintilimab (200 mg) combined with the SOX regimen (oxaliplatin 130 mg/m² and S-1, with the initial dose determined based on body surface area). Additionally, apatinib (250 mg) will be administered orally once daily during the first three neoadjuvant cycles. 2. Control Group: Participants will receive treatment with the sintilimab combined with the SOX regimen. This treatment will be administered for three to four cycles prior to surgery, followed by radical surgery, including D2 or D2+ lymph node dissection. Surgery is scheduled four weeks after the last neoadjuvant therapy (NAT) cycle. Within 3 to 6 weeks post-surgery, patients will begin adjuvant SOX chemotherapy. Postoperative patients will receive four cycles of adjuvant SOX chemotherapy, administered every three weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
682
Sintilimab: 200mg, iv, day 1 Oxaliplatin: 130 mg/m², iv, day 1 S-1: 40-60 mg/m², po, day 1-14 (BSA \< 1.25 m², 40 mg bid, 1.25 m² ≤ BSA \< 1.5 m², 50 mg bid, BSA ≥ 1.5 m², 60 mg bid) Apatinib: 250mg, po, day1-21, for 3 cycles preoperatively
Sintilimab: 200mg, iv, day 1 Oxaliplatin: 130 mg/m², iv, day 1 S-1: 40-60 mg/m², po, day 1-14 (BSA \< 1.25 m², 40 mg bid, 1.25 m² ≤ BSA \< 1.5 m², 50 mg bid, BSA ≥ 1.5 m², 60 mg bid)
First Hospital of Lanzhou University
Lanzhou, Gansu, China
RECRUITINGGansu Provincial Hospital
Lanzhou, Gansu, China
RECRUITINGLanzhou University Second Hospital
Lanzhou, Gansu, China
RECRUITINGThe Gastrointestinal Surgery Department, Sun Yat-sen University Cancer Center Gansu Hospital
Lanzhou, Gansu, China
RECRUITINGPathological complete response (pCR) rate
Pathological Complete Response rate (pCR) refers to the proportion of cases in which no active cancer cells are detected in the surgically resected tumor tissue after neoadjuvant therapy, as assessed using the Becker TRG grading system.
Time frame: Enrollment to surgical treatment takes about 4 months.
Major pathological response (MPR) rate
Major Pathological Response (MPR) rate refers to the proportion of patients who, after receiving neoadjuvant therapy, are assessed using the Becker TRG grading system and have less than 10% residual viable cancer cells in the surgically resected tumor tissue.
Time frame: Enrollment to surgical treatment takes about 4 months.
Objective response rate (ORR)
The Objective Response Rate (ORR) is a widely used efficacy measure in clinical trials, especially in oncology, to assess the objective changes in tumors in response to treatment. It represents the proportion of patients whose tumors have achieved either a Complete Response (CR) or a Partial Response (PR). The assessment of ORR is typically based on the internationally standardized criteria for evaluating solid tumor responses, known as RECIST v1.1 (Response Evaluation Criteria in Solid Tumors, version 1.1).
Time frame: From enrollment to preoperative imaging assessment, it takes approximately 4 months.
3-year survival rate (3-year OS rate)
The 3-year survival rate (3-year OS rate) is the percentage of patients who survive 3 years after enrollment.
Time frame: From the point of enrollment to the end of the 3-year follow-up period.
Adverse Event
For the classification and grading of Adverse Events (AEs), the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0 is generally used as the standard.
Time frame: From enrollment to the completion or discontinuation of treatment, an estimated duration of eight months is expected.
Disease control rate (DCR)
DCR is the percentage of patients with measurable disease at baseline who experience CR, PR, or SD, as determined by BICR using RECIST v1.1 guidelines.
Time frame: From enrollment to preoperative imaging assessment, it takes approximately 4 months.
3-year event-free survival rate (3-year EFS rate).
3-year EFS rate is defined as the proportion of patients who remain free from disease recurrence, progression, or death over a three-year period, without experiencing any predefined adverse events.
Time frame: From the point of enrollment to the end of the 3-year follow-up period.
R0 resection rate
The R0 resection rate is defined as the proportion of patients in whom no cancer cells are detected at the surgical margins under microscopic examination, indicating complete removal of the tumor with no visible residual cancer, both macroscopically and microscopically.
Time frame: Enrollment to surgical treatment takes about 4 months.
Downstaging rates of T, N, TNM stages.
The tumor downstage rate represents the percentage of patients whose overall ypTNM, T, or N stage has decreased from their baseline cTNM, cT, or cN stage. Tumor staging was assessed using baseline cTNM and postoperative ypTNM evaluations according to the 8th edition of the AJCC Gastric Cancer Staging Manual.
Time frame: Enrollment to preoperative imaging assessment takes about 4 months.
Surgery-related complications
Surgery-related complications are defined as any complications occurring within 30 days following surgery, classified according to the Clavien-Dindo Classification of Surgical Complications. These complications include, but are not limited to, vomiting, fever, incision infection, post-operative pneumonia, anastomotic hemorrhage or leakage, chylous leakage, pneumonia, intestinal obstruction, and other related issues.
Time frame: Enrollment to surgical treatment takes about 4 months.
Programmed death-ligand 1 combined positive score (PD-L1 CPS)
PD-L1 expression acts as a predictive biomarker for assessing treatment efficacy, encompassing metrics such as the pathologic complete response rate (pCR rate), major pathologic response rate (MPR rate), and both the 3-year overall survival rate (OS rate) and 3-year Event-Free Survival (EFS) rate.
Time frame: After enrollment, the measurements were completed.
Microsatellite instability (MSI) status
Microsatellite instability status acts as a predictive biomarker for assessing treatment efficacy, encompassing metrics such as the pathologic complete response rate (pCR rate), major pathologic response rate (MPR rate), and both the 3-year overall survival rate (OS rate) and 3-year Event-Free Survival (EFS) rate.
Time frame: After enrollment, the measurements were completed.
The ratio of NG2+/CD31
The ratio of NG2+/CD31 acts as a predictive biomarker for assessing treatment efficacy, encompassing metrics such as the pathologic complete response rate (pCR rate), major pathologic response rate (MPR rate), and both the 3-year overall survival rate (OS rate) and 3-year Event-Free Survival (EFS) rate.
Time frame: Enrollment to surgical treatment takes about 4 months.
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