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.
Type of Participant and Disease Characteristics
Patients must have a pathologically confirmed diagnosis of HER-2 negative tumor and intestinal type gastric or gastroesophageal junction adenocarcinoma according to Lauren's histological subtypes.
Patients must have previously untreated locally advanced gastric or gastroesophageal junction adenocarcinoma (stage cT2 to cT4), with lymph nodes ranging from N0 to N3 and no evidence of metastatic disease (M0).
Patients with Siewert type 2 or 3 tumors are eligible. Enrollment of participants with Siewert type 1 tumors will be limited to those for whom the planned treatment is perioperative chemotherapy and resection.
Medical Conditions
Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
Has a known additional malignancy that is progressing or has required active treatment within the past 5 years (except for cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, or carcinoma in situ that has undergone potentially curative therapy).
Has an active infection requiring systemic therapy.
Parallel
Neoadjuvant apatinib combined with sintilimab and perioperative SOX
DrugSintilimab: 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
Neoadjuvant sintilimab combined with perioperative SOX
DrugSintilimab: 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)
Pathological 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.
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.
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).
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.
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.
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Zuoyi Jiao
Lead sponsor
Lanzhou University Second Hospital
Sponsor institution
