Perioperative Chemotherapy With Low-Dose Radiotherapy and Tislelizumab for Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Official title

A Phase II Multicenter Randomized Controlled Trial of Perioperative Chemotherapy Combined With Low-Dose Radiotherapy and Tislelizumab Versus Chemotherapy Alone in Patients With Locally Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

Overview

This study is a prospective, multicenter, randomized, phase II clinical trial enrolling patients with resectable locally advanced gastric or gastroesophageal junction adenocarcinoma. The study aims to compare the efficacy and safety of perioperative chemotherapy combined with low-dose radiotherapy and tislelizumab versus perioperative chemotherapy alone in this patient population.

Interventions

• Drug Low Dose Radiotherapy Combined with Tislelizumab and Chemotherapy
  Chemotherapy: Oxaliplatin 130 mg/m² on days 1 and 22 plus capecitabine 1000 mg/m² twice daily on days 1-14, for a total of 3 cycles.Tislelizumab: 200 mg administered concurrently with chemotherapy on days 1 and 22 via intravenous infusion, for a total of 3 cycles. Low Dose Radiotherapy: Initiated within one week after the start of chemotherapy; total dose (DT): 30 Gy.
• Drug Chemotherapeutic Agent
  Chemotherapy: Oxaliplatin 130 mg/m² on days 1 and 22 plus capecitabine 1000 mg/m² twice daily on days 1-14, for a total of 3 cycles.
• Device low-dose radiotherapy
  Radiotherapy: Initiated within one week after the start of chemotherapy; total dose (DT): 30 Gy.

Primary outcome measures

• Pathological Complete Response (pCR) Rate (ITT Population) [Time frame: At the time of surgery following completion of neoadjuvant therapy, based on pathological evaluation of the resected surgical specimen.]

Secondary outcome measures (4)

• Pathological Complete Response (pCR) Rate (Surgical Population) [Time frame: At the time of surgery following completion of neoadjuvant therapy, based on pathological evaluation of the resected surgical specimen.]
• R0 Resection Rate [Time frame: At the time of surgery, based on pathological evaluation of the resected surgical specimen.]
• Event-Free Survival (EFS) [Time frame: From the date of randomization until the occurrence of disease progression, recurrence, death, or end of follow-up, whichever occurs first, assessed up 60 months.]
• Overall Survival (OS) [Time frame: From the date of randomization until death from any cause or end of follow-up, whichever occurs first, assessed up to 60 months.]

Eligibility criteria

Inclusion criteria

1.Voluntary participation with written informed consent obtained; 2. Histologically confirmed gastric or gastroesophageal junction adenocarcinoma (Siewert type II/III) by endoscopic biopsy (pathology from outside institutions must be reviewed by the study center); 3. Staged as cT1-2N1-3M0 or cT3-4aN0-3M0 according to the AJCC 8th edition, based on endoscopy and imaging (CT, MRI, or PET-CT); 4. Age ≥20 and ≤80 years, male or female; ECOG performance status of 0-1; 5. Presence of measurable and/or non-measurable disease per RECIST v1.1; 6.No prior systemic antitumor therapy, including chemotherapy, radiotherapy, targeted therapy, immunotherapy, biologic therapy, local therapy, or investigational agents; Adequate organ function (no blood products or growth factors within 2 weeks prior to screening); 7. Women of childbearing potential must have a negative pregnancy test within 72 hours prior to first dosing and agree to use effective contraception during the study and for 5 months after the last dose; men with partners of childbearing potential must use effective contraception during the study and for 7 months after the last dose.

Exclusion criteria

• History of surgery for gastric or gastroesophageal junction tumors;
• Prior history of fistula formation caused by invasion of the primary tumor; 3.High risk of gastrointestinal bleeding or perforation;

4.Poor nutritional status, defined as BMI <18.5 kg/m² or PG-SGA score ≥9; 5. Major surgery or severe trauma within 4 weeks prior to first study drug administration; Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage; 6. Prior or ongoing treatment with anti-PD-1/PD-L1 antibodies, chemotherapy, radiotherapy, or targeted therapy; 7. Use of any investigational drug within 4 weeks prior to first study drug administration; Requirement for systemic corticosteroids; 8. Prior receipt of antitumor vaccines or live vaccines within 4 weeks before first study drug administration; 9. Active autoimmune disease or history of autoimmune disease; 10.History of immunodeficiency, including HIV infection, other acquired or congenital immunodeficiency, solid organ transplantation, or allogeneic bone marrow transplantation; 11.Any condition requiring systemic corticosteroid or immunosuppressive therapy within 14 days prior to treatment, except for minimal systemic absorption routes or short-term (≤7 days) prophylactic use; 12.Uncontrolled clinically significant cardiac disease, including NYHA class II or higher heart failure, unstable angina, myocardial infarction within 1 year, or clinically significant arrhythmias requiring intervention; 13.Severe infection (CTCAE grade >2) within 4 weeks prior to treatment, including infections requiring hospitalization; evidence of active pulmonary infection at baseline imaging or infections requiring antibiotics within 2 weeks prior to enrollment (prophylactic antibiotics excluded); 14.History of interstitial lung disease, noninfectious pneumonitis, pulmonary fibrosis, or other uncontrolled acute pulmonary disease; 15.Active tuberculosis, history of active tuberculosis within 1 year prior to enrollment, or inadequately treated tuberculosis more than 1 year prior; 16.Active hepatitis B (HBV DNA ≥2,000 IU/mL) or hepatitis C infection (HCV antibody positive with detectable HCV RNA); 17.Any condition requiring systemic corticosteroid or immunosuppressive therapy within 14 days prior to treatment, except for minimal systemic absorption routes or short-term (≤7 days) prophylactic use; 18.Uncontrolled clinically significant cardiac disease, including NYHA class II or higher heart failure, unstable angina, myocardial infarction within 1 year, or clinically significant arrhythmias requiring intervention; 19.Severe infection (CTCAE grade >2) within 4 weeks prior to treatment; History of interstitial lung disease, noninfectious pneumonitis, pulmonary fibrosis, or other uncontrolled acute pulmonary disease; 20.Active tuberculosis, history of active tuberculosis within 1 year prior to enrollment, or inadequately treated tuberculosis more than 1 year prior; 21.Active hepatitis B (HBV DNA ≥2,000 IU/mL) or hepatitis C infection (HCV antibody positive with detectable HCV RNA); 22.Grade >1 abnormalities in serum sodium, potassium, or calcium within 2 weeks prior to enrollment that cannot be corrected with treatment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07408609 · GAS-Jiangsu04

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗