XELOX Combined With Sintilimab and HBO for Advanced or Metastatic GC/GEJC

NCT06742411 | Recruiting Phase 1

• 1 other identifier: WCH20242269
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 2

Brief Summary

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 Advanced 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.

Conditions

Gastric (Stomach) Cancer

Outcome Measures

Primary Outcomes (1)

• ORR

  The primary outcome measure is the overall response rate (ORR), defined as the proportion of patients achieving a complete response (CR) or partial response (PR) as assessed by RECIST 1.1 criteria. ORR will be evaluated based on imaging and clinical assessments conducted during the study.

  ORR will be assessed after 4 to 6 cycles of treatment (approximately 12 to 18 weeks). Evaluation will include imaging performed at baseline and at the end of the treatment cycles to determine the tumor response.

Secondary Outcomes (7)

• Progression-Free Survival (PFS)

  From the start of treatment to the first disease progression or death, assessed up to approximately 24 months.

• Disease Control Rate (DCR)

  After 4-6 cycles of treatment (approximately 12-18 weeks).

• Downstaging Rate

  After 4-6 cycles of treatment (approximately 12-18 weeks).

• 2-Year Disease-Free Survival (DFS)

  From the start of treatment to 2 years post-treatment.

• 2-Year Overall Survival (OS)

  From the start of treatment to 2 years post-treatment.

Study Arms (1)

XELOX+Sintilimab+HBOT

EXPERIMENTAL

Patients will receive the XELOX regimen, consisting of oxaliplatin (130 mg/m² IV on Day 1) and capecitabine (1000 mg/m² orally twice daily for 14 days, repeated every 3 weeks), combined with sintilimab (200 mg IV on Day 1 every 3 weeks) and hyperbaric oxygen therapy (HBOT) administered alongside the XELOX regimen. Treatment will be administered for 4 to 6 cycles. Following the initial treatment phase, patients will be evaluated for response. If disease progression is observed, patients will exit the study and receive subsequent treatments as deemed appropriate. For patients with stable disease or a response to therapy, maintenance treatment with capecitabine and sintilimab will continue until the occurrence of a study endpoint or other specified criteria.

Drug: XELOX+Sintilimab+HBOT

Interventions

XELOX+Sintilimab+HBOT DRUG

Patients will receive the XELOX regimen, consisting of oxaliplatin (130 mg/m² IV on Day 1) and capecitabine (1000 mg/m² orally twice daily for 14 days, repeated every 3 weeks), combined with sintilimab (200 mg IV on Day 1 every 3 weeks) and hyperbaric oxygen therapy (HBOT) administered alongside the XELOX regimen. Treatment will be administered for 4 to 6 cycles. Following the initial treatment phase, patients will be evaluated for response. If disease progression is observed, patients will exit the study and receive subsequent treatments as deemed appropriate. For patients with stable disease or a response to therapy, maintenance treatment with capecitabine and sintilimab will continue until the occurrence of a study endpoint or other specified criteria.

XELOX+Sintilimab+HBOT

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis: Histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (including signet ring cell carcinoma, mucinous adenocarcinoma, and hepatoid adenocarcinoma).
• Disease status: The presence of metastatic disease, attributable to either recurrence or distant dissemination, was established through a combination of radiologic or surgical assessments.
• Survival Expectancy: Predicted to live more than 3 months. 4.Age: 18-75 years. 5.Prior treatments:
• There are no previous antitumor treatments (chemotherapy, radiotherapy, targeted therapy, immunotherapy, interventional therapy, etc.).
• If patients previously received adjuvant or neoadjuvant therapy, the last treatment must have been completed at least 6 months before randomization, with no recurrence or disease progression during treatment.
• Palliative radiotherapy is allowed if it is completed at least 2 weeks before the first study treatment.
• The use of prior anti-tumor traditional Chinese medicine is allowed if it is discontinued at least 2 weeks before randomization.
• Performance Status: ECOG PS ≤1. 7.Assessable lesion: At least one measurable lesion per the RECIST 1.1 criteria.
• Pathological samples: Patients whose archived or fresh pathological tissue was obtained within 6 months before signing informed consent, which was sufficient for PD-L1 testing with obtainable results, were included.
• Organ function:
• Hematology (no transfusion or G-CSF use within 14 days before screening):
• Hemoglobin ≥90 g/L. Absolute neutrophil count (ANC) ≥1.5×10⁹/L. Platelet count ≥75×10⁹/L.
• Biochemistry (no albumin use within 14 days before screening):
• Albumin ≥28 g/L. Total bilirubin ≤1.5×ULN. AST and ALT levels were ≤3×ULN (≤5×ULN if liver metastasis was present). creatinine ≤1.5×ULN. (3)Coagulation: INR or PT ≤1.5×ULN. APTT ≤1.5×ULN. 10.Systemic treatment history: No systemic treatment (including adjuvant/neoadjuvant) was given within the past 6 months after sample collection for randomization.

You may not qualify if:

• Contraception: Strict contraception measures. 13.Consent and Compliance: Signed informed consent, willing and able to comply with study visits, treatments, lab tests, and procedures.
• HER2 status: HER2-positive (HER2 3+ or 2+ \& FISH+).
• Tumor type: Nonadenocarcinoma gastric cancers, including squamous cell carcinoma, undifferentiated carcinoma, or mixed histological types.
• CNS Metastasis: Uncontrolled or symptomatic active CNS metastasis (e.g., clinical symptoms, brain edema, spinal cord compression, carcinomatous meningitis, soft meningeal disease, or progressive growth).
• Fluid accumulation: Uncontrolled pleural effusion or ascites treated with drainage within 14 days before randomization; symptomatic or moderate to large pericardial effusion.
• Weight loss: Weight loss \>20% within 2 months before randomization.
• Recent treatments:
• (1)Major surgery within 28 days before randomization (diagnostic biopsies and PICC placement allowed).
• (2)Immunosuppressive drugs should be used within 7 days before randomization, excluding nasal/inhaled corticosteroids or physiological-dose systemic steroids (≤10 mg/day prednisone or equivalent).
• (3)Live attenuated vaccines were administered within 28 days before randomization, during the study, or within 60 days after treatment ended.
• (4)Antitumor treatments were administered within 28 days before randomization (chemotherapy, radiotherapy, immunotherapy, endocrine therapy, targeted therapy, biological therapy, or tumor embolization).
• Other Malignancies: Patients were diagnosed with any other malignancy within 3 years before study entry, except for localized and cured basal cell carcinoma, squamous or superficial bladder carcinoma, cervical carcinoma in situ, ductal carcinoma in situ of the breast, and papillary thyroid carcinoma.
• Autoimmune Diseases: Any active, known, or suspected autoimmune disease. Stable conditions not requiring systemic immunosuppression are allowed (e.g., type I diabetes; hypothyroid diabetes managed with hormone replacement; and skin diseases not needing systemic treatment, such as vitiligo, psoriasis, and alopecia).
• Neurological/Psychiatric Conditions: Uncontrolled epilepsy, congenital spherocytosis, claustrophobia, or angle-closure glaucoma.
• Immune therapy history: Prior treatment with anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies, or other T-cell costimulation/checkpoint pathway drugs.

Sponsors & Collaborators

• West China Hospital: lead

Study Sites (2)

West China Hospital of Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

NOT YET RECRUITING

Related Publications (1)

• Li W, Zhang P, Cheng M, Wei J, Xu M, Li D, Song S, Liu M, Huang C, Zhu L. XELOX combined with sintilimab and hyperbaric oxygen therapy for advanced or metastatic gastric/gastroesophageal junction adenocarcinoma: study protocol for a prospective, single-arm, phase Ib/II clinical trial. Front Immunol. 2026 Jan 12;16:1672725. doi: 10.3389/fimmu.2025.1672725. eCollection 2025.

  PMID: 41601634 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Central Study Contacts

Ming Liu, M.D

CONTACT

+8618980606324; mingliu721@aliyun.com

Cheng Huang, M.D

CONTACT

+8618980603143

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: December 16, 2024
• First Posted: December 19, 2024
• Study Start: December 31, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 7, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)