Gastric (Stomach) Cancer
Conditions
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.
Detailed description
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 Advanced 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.
Interventions
DRUGXELOX+Sintilimab+HBOT
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.
Sponsors
West China Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1.Diagnosis: Histologically or cytologically confirmed adenocarcinoma of the stomach or gastroesophageal junction (including signet ring cell carcinoma, mucinous adenocarcinoma, and hepatoid adenocarcinoma). 2.Disease status: The presence of metastatic disease, attributable to either recurrence or distant dissemination, was established through a combination of radiologic or surgical assessments. 3.Survival Expectancy: Predicted to live more than 3 months. 4.Age: 18-75 years. 5.Prior treatments: 1. There are no previous antitumor treatments (chemotherapy, radiotherapy, targeted therapy, immunotherapy, interventional therapy, etc.). 2. 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. 3. Palliative radiotherapy is allowed if it is completed at least 2 weeks before the first study treatment. 4. The use of prior anti-tumor traditional Chinese medicine is allowed if it is discontinued at least 2 weeks before randomization. 6.Performance Status: ECOG PS ≤1. 7.Assessable lesion: At least one measurable lesion per the RECIST 1.1 criteria. 8.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. 9.Organ function: 1. 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. 2. 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. 11.Toxicity: Prior antitumor treatment or surgery-related acute toxic reactions were resolved to grade 0-1 per NCI CTCAE v5.0 or to levels specified by the inclusion/
Exclusion criteria
. 12.Contraception: Strict contraception measures. 13.Consent and Compliance: Signed informed consent, willing and able to comply with study visits, treatments, lab tests, and procedures.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ORR | 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. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) | After 4-6 cycles of treatment (approximately 12-18 weeks). | Disease control rate (DCR) is defined as the proportion of patients who achieve a complete response (CR), partial response (PR), or stable disease (SD) as assessed by RECIST 1.1 criteria. |
| Downstaging Rate | After 4-6 cycles of treatment (approximately 12-18 weeks). | Downstaging rate is defined as the proportion of patients whose tumors are successfully reduced in stage, enabling resection or improved therapeutic options, as determined by imaging and clinical evaluations. |
| 2-Year Disease-Free Survival (DFS) | From the start of treatment to 2 years post-treatment. | Two-year disease-free survival (DFS) is defined as the percentage of patients who remain free of disease recurrence after achieving disease control or response to treatment within the study period. |
| Progression-Free Survival (PFS) | From the start of treatment to the first disease progression or death, assessed up to approximately 24 months. | Progression-free survival (PFS) is defined as the time from the start of treatment to the first documented disease progression, as assessed by RECIST 1.1 criteria, or death from any cause, whichever occurs first. |
| Adverse Events | From the start of treatment to the end of the study (up to approximately 24 months). | Safety will be assessed based on the incidence, nature, and severity of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) graded according to the NCI-CTCAE v5.0. |
| Quality of Life (QoL) | Baseline, every 3 weeks during treatment, and every 12 weeks post-treatment, up to 24 months. | Quality of life (QoL) will be evaluated using validated patient-reported outcome measures, such as the EORTC QLQ-C30 questionnaire, to assess the physical, emotional, and functional well-being of patients during and after treatment. |
| 2-Year Overall Survival (OS) | From the start of treatment to 2 years post-treatment. | Two-year overall survival (OS) is defined as the percentage of patients who are still alive 2 years after initiating treatment, regardless of disease progression. |
Countries
China
Contacts
Primary ContactMing Liu, M.D
Backup ContactCheng Huang, M.D
Outcome results
None listed