Sintilimab Combined With SOX Versus SOX as Adjuvant Therapy for Patients With Stage pIIIC or dMMR/MSI-H Stage pIIIA/IIIB Gastric or Gastroesophageal Junction Adenocarcinoma: A Single-center, Randomized Controlled Phase II Clinical Trial
This study aims to explore the efficacy and safety of sintilimab combined with SOX versus SOX alone as adjuvant therapy for patients with pIIIC stage or dMMR/MSI-H pIIIA/IIIB stage gastric/gastroesophageal junction adenocarcinoma. A total of 276 subjects are planned to be enrolled in this study. Patients will be randomly assigned in a 1:1 ratio to receive up to 8 cycles of sintilimab combined with SOX or SOX alone as adjuvant therapy.
• Signed written informed consent.
• Male or female, age ≥18 years.
• Histopathologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (GEJ).
• Diagnosed with pTNM stage IIIC or pTNM stage IIIA/IIIB.
• Diagnosed with mismatch repair deficiency (dMMR) by immunohistochemistry (IHC) of biopsy tissue or microsatellite instability-high (MSI-H) by genetic sequencing.
• Underwent D2 or more extensive radical resection and achieved R0 resection.
• Able to swallow tablets normally.
• ECOG performance status 0-1.
• Life expectancy \>6 months.
⁃ Adequate organ function, subjects must meet the following laboratory criteria:
∙ Absolute neutrophil count (ANC) ≥1.5×10\^9/L without granulocyte colony-stimulating factor within the past 14 days.
‣ Platelets ≥100×10\^9/L without transfusion within the past 14 days.
‣ Hemoglobin \>9 g/dL without transfusion or erythropoietin use within the past 14 days.
‣ Total bilirubin ≤1.5×ULN; if total bilirubin \>1.5×ULN but direct bilirubin ≤ULN, enrollment is also permitted.
‣ Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN.
‣ Serum creatinine ≤1.5×ULN and creatinine clearance (calculated by Cockcroft-Gault formula) ≥60 ml/min.
‣ Good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN.
‣ Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within normal range. If baseline TSH is outside the normal range, subjects with total T3 (or FT3) and FT4 within the normal range may also be enrolled.
‣ Cardiac enzyme panel within normal range (isolated laboratory abnormalities deemed clinically insignificant by the investigator are also permitted for enrollment).
⁃ For female subjects of childbearing potential, a urine or serum pregnancy test must be negative within 3 days prior to the first dose of study drug (Cycle 1 Day 1). If the urine pregnancy test cannot be confirmed as negative, a serum pregnancy test is required. Non-childbearing potential is defined as postmenopausal for at least 1 year, or surgically sterile or hysterectomy.
⁃ If at risk of conception, all subjects (male or female) must use contraceptive measures with a failure rate of \<1% per year throughout the treatment period and for 120 days after the last dose of study drug (or 180 days after the last dose of chemotherapy).