XELOX Combined With Sintilimab and HBO for Advanced GC/GEJC

This study investigates the efficacy and safety of XELOX chemotherapy combined with sintilimab and hyperbaric oxygen therapy (HBOT) as a first-line treatment for patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma. The trial comprises two phases: a phase Ib study to determine the optimal HBOT regimen and assess safety and tolerability, followed by a phase II study to evaluate the overall response rate (ORR). Secondary outcomes include progression-free survival (PFS), disease control rate (DCR), 2-year disease-free survival (DFS), 2-year overall survival (OS), safety, and quality of life. This study aims to provide a novel approach for enhancing therapeutic efficacy and improving patient outcomes by leveraging HBOT to address tumor hypoxia and augment the effects of chemotherapy and immune checkpoint inhibitors.

This is a prospective, single-arm, phase Ib/II clinical trial designed to evaluate the safety and efficacy of the XELOX regimen combined with sintilimab and hyperbaric oxygen therapy (HBOT) in patients with unresectable or metastatic gastric and gastroesophageal junction adenocarcinoma.

In the phase Ib portion, 9 patients will be enrolled to identify the optimal HBOT protocol and assess the safety and tolerability of the combined treatment. The dose and schedule of HBOT will be refined based on observed safety data and adverse events.

In the phase II portion, approximately 48 patients will be enrolled to further evaluate the efficacy of the XELOX plus sintilimab and HBOT combination. Patients will receive treatment in 3-week cycles, with HBOT administered alongside chemotherapy and immunotherapy. The primary endpoint of the phase II study is the overall response rate (ORR) assessed per RECIST 1.1 criteria.Secondary endpoints include progression-free survival (PFS), disease control rate (DCR), 2-year disease-free survival (DFS), 2-year overall survival (OS), safety profile, and patient-reported outcomes related to quality of life. Exploratory endpoints will focus on biomarker analysis and the role of HBOT in modulating tumor hypoxia.This study aims to explore whether HBOT can enhance the efficacy of chemotherapy and immunotherapy by addressing tumor hypoxia, a known factor contributing to therapy resistance in gastric and gastroesophageal junction cancers. The findings from this trial may provide insights into a novel multimodal treatment strategy for improving patient outcomes in advanced disease settings.

Eligibility Criteria:
Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma, including signet ring cell carcinoma, mucinous adenocarcinoma, and hepatoid adenocarcinomag and surgical evaluations confirming unresectable recurrent or metastatic disease .
2. Expec of more than 3 months .
3. Age between 18 a inclusive, with no restriction on gender .
4. No prior systemic treatmentd or metastatic gastric or gastroesophageal adenocarcinoma. Patients who received adjuvant or neoadjuvant therapy for earlier-stage disease must have completed treatment at least 6 months before randomization without evidence of disease recurrence or progression .
5. ECOG performance status of 0-1 .
6. Ateasurable lesion according to RECISia .
7. Availability of archival tumor tissue or newly obtained biop testing within 6 months prior to consent .
8. Adequate organ function, including:

Hemoglobin ≥ 90 g/L Absolil count (ANC) ≥ 1.5 × 10⁹/L Platelet count ≥ 75 × 10⁹/L Albumin ≥ 28 g/L Total bilirubin ≤ 1.5 × upper limit of normal (ULN) AST and ALT ≤ 3 × ULN (≤ 5 × ULN for patients with liver metastases) Creatinine ≤ 1.5 × ULN .

Exclusion Criteria:

1. Known HER2-positive status (HER2 3+ or 2+ with FISH posi History of allergic reactions to study drugs or monoclonal antibodies .
2. Active, untreated es or symptomatic CNS involvement, unless adequately controlled for at leaefore randomization .
3. Uncontrolled pleural effusion, ascites, or pericardial effusion requiring drainage within 14 days before randomizative infection or unexplained fever \> 38.5°C during screening .
4. Autoimmune diseases requiring systemic immunosuppressive Significant cardiovascular disease within the past 6 months, includal infarction or unstable angina .
5. Prior treatment with PD-1/PD-L1r CTLA-4 inhibitors .
6. Pregnant or breastfeeding women, and women of childbearing potential not willing to use medved contraception .
7. Any other condition or laboratory abnormalitsignificantly interfere with the conduct or interpretation of the study or place the patient at undue risk as determined by tor.