A Prospective, Open-label, Randomized, Controlled Phase II Clinical Trial Exploring the Efficacy and Safety of Thymosin Alpha 1 Combined With PD-1 Monoclonal Antibody and Neoadjuvant Chemoradiotherapy for cStage III Gastroesophageal Junction Adenocarcinoma.
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: Immunomodulation group (n=32): 3 cycles of slulimab combined with SOX combined with radiotherapy and 9 weeks of neoadjuvant thymosin; Radiochemoimmunotherapy group (n=16): 3 cycles of slulimab combined with SOX combined with radiotherapy; Radiotherapy was initiated 2-5 days after the start of the second cycle of immunochemotherapy. A 5-10 mm extravasation was made from the endoscopically marked tumor boundary and adjacent metastatic lymph nodes to form a central tumor volume (CTV), and a 5-10 mm extravasation was made to form a partial tumor volume (PTV). The planned PTV treatment time was 44 Gy/22 fractions per minute (F), 5 fractions per week (F/W). 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 the safety of neoadjuvant therapy: the incidence of ≥ grade 3 treatment-related adverse events (TRAEs) during the perioperative period (from the start of neoadjuvant therapy to one month postoperatively). 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.
• Aged 18 to 75 years, regardless of gender. Histologically confirmed gastroesophageal junction (GEJ) cancer that has received neoadjuvant therapy, with pathology confirming it is predominantly adenocarcinoma. Only Siewert Type III and Siewert Type II cases that do not require combined thoracotomy are eligible.
• Tumor stage confirmed as cStage III, suitable for curative R0 resection, as determined by an evaluation by a gastrointestinal surgeon and a radiologic technician prior to enrollment. Patients must agree to undergo Neoadjuvant chemoimmunoradiotherapy and radical surgery .
• Patients must not have received prior systemic treatment for the current disease, including surgery, anti-tumor chemotherapy, radiotherapy, or immunotherapy.
• Expected survival of ≥6 months. Measurable tumor lesions as defined by RECIST v1.1 criteria . Preoperative ECOG performance status score of 0 or 1. Good cardiac function, capable of undergoing a curative resection. If there are clinical indications, patients with underlying ischemic, valvular heart disease, or other serious heart conditions should undergo preoperative assessment by a cardiologist.
• Normal major organ function, with the following laboratory criteria:
• Absolute neutrophil count (ANC) ≥ 1.2 x 10\^9/L in the absence of granulocyte colony-stimulating factor use within the past 14 days.
• Platelet count ≥ 100 x 10\^9/L in the absence of blood transfusion within the past 14 days.
• Hemoglobin \> 8 g/dL in the absence of blood transfusion or erythropoietin use within the past 14 days.
• Total bilirubin ≤ 1.5 × the upper limit of normal (ULN); if total bilirubin \> 1.5 × ULN but direct bilirubin ≤ ULN, inclusion is permitted.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN.
• Serum creatinine ≤ 1.5 × ULN and creatinine clearance (calculated by the Cockcroft-Gault formula) ≥ 60 mL/min.
• Coagulation function defined by international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN.
• Normal thyroid function, defined by thyroid-stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, patients with normal total T3 (or FT3) and FT4 levels may still be eligible.
• Normal range for myocardial enzyme profile (patients with isolated laboratory abnormalities deemed clinically insignificant by the investigator may still be included).
• Thyroid function tests (TSH, FT3/FT4) within normal limits or with minor clinically insignificant abnormalities.
• Weight ≥ 40 kg (inclusive) or BMI \> 18.5. Female Patients:Must be post-menopausal (no menses for at least one year without other causes) or surgically sterilized (removal of ovaries and/or uterus).Women of childbearing potential must have a negative pregnancy test within 7 days prior to the first dose.Agree to use highly effective contraception (annual failure rate \< 1%) or abstain from heterosexual intercourse from the time of informed consent until at least 120 days after the last dose of the study drug or 9 months after surgery.
• The participant has read, understood, and signed the informed consent form.