Clinical trial NCT06742411: XELOX Combined With Sintilimab and HBO for Advanced or Metastatic GC/GEJC
Official title: A Phase Ib/II Clinical Trial of the XELOX Regimen Combined With Sintilimab and Hyperbaric Oxygen Therapy for the Treatment of Advanced or Metastatic Gastric and Gastroesophageal Junction Adenocarcinoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Gastric (Stomach) Cancer
Lead sponsor: West China Hospital
Sponsor class: OTHER
First posted: 2024-12-19
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Exclusion criteria:

1. HER2 status: HER2-positive (HER2 3+ or 2+ \& FISH+).
2. Tumor type: Nonadenocarcinoma gastric cancers, including squamous cell carcinoma, undifferentiated carcinoma, or mixed histological types.
3. 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).
4. Fluid accumulation: Uncontrolled pleural effusion or ascites treated with drainage within 14 days before randomization; symptomatic or moderate to large pericardial effusion.
5. Weight loss: Weight loss \>20% within 2 months before randomization.
6. 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).

7.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.

8.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).

9.Neurological/Psychiatric Conditions: Uncontrolled epilepsy, congenital spherocytosis, claustrophobia, or angle-closure glaucoma.

10.Immune therapy history: Prior treatment with anti-PD-1/PD-L1 antibodies, anti-CTLA-4 antibodies, or other T-cell costimulation/checkpoint pathway drugs.

11.Bleeding/thrombosis events: significant bleeding symptoms or tendencies within 3 months before randomization; gastrointestinal perforation or fistula within 6 months; thrombotic events (e.g., stroke, deep vein thrombosis, pulmonary embolism) within 6 months.

12.Major Vascular Disease: Major vascular disease within 6 months before study treatment (e.g., aortic aneurysm needing surgery or recent peripheral arterial thrombosis).

13.Wounds and fractures: Severe, unhealed, or open wounds; active ulcers; or untreated fractures.

14.Neuropathy: Peripheral neuropathy \>Grade 1. 15.Intestinal Obstruction: History of intestinal obstruction or related symptoms within 6 months before study treatment. Patients treated surgically to resolve incomplete obstructions at initial diagnosis may be included.

16.Systemic diseases: Interstitial lung disease, noninfectious inflammation, or uncontrolled systemic diseases (e.g., diabetes, hypertension, pulmonary fibrosis, acute pneumonia).

17.Drug Allergies: Patients with known severe allergic reactions to the study drugs or any monoclonal antibodies.

18.HIV/AIDS: HIV infection or known AIDS. 19.Hepatitis: Untreated active hepatitis B (HBV-DNA ≥500 IU/ml), hepatitis C (HCV-RNA above the detection limit), or coinfection with HBV and HCV.

20.Cardiac conditions: Myocardial infarction, severe/unstable angina, NYHA Class II or higher heart failure, significant arrhythmias, or congestive heart failure within 6 months before randomization.

21.Hypertension: Poorly controlled hypertension despite treatment (systolic BP \>140 mmHg or diastolic BP \>90 mmHg).

22.Infections and Fever: Systemic antibiotic use ≥7 days within 4 weeks before randomization or unexplained fever \>38.5°C during screening/before the first dose (tumor-related fever allowed on the basis of the investigator's judgment).

23.Transplant history: Known history of allogeneic organ or hematopoietic stem cell transplantation.

24.Other Clinical Trials: Participation in any other drug clinical trial within 4 weeks before randomization or within 5 half-lives of the last study drug.

25.Substance Abuse: History of psychiatric drug abuse or drug addiction. 26.Other Severe Conditions: Any other serious physical or mental illness, abnormal lab tests increasing study risk or interfering with results, or deemed unsuitable by the investigator.

27.The pulmonary conditions were as follows: treated pneumothorax, severe emphysema, or pulmonary bullae.

Primary outcomes:
measure: ORR
timeFrame: 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:
measure: Progression-Free Survival (PFS)
timeFrame: From the start of treatment to the first disease progression or death, assessed up to approximately 24 months.
measure: Disease Control Rate (DCR)
timeFrame: After 4-6 cycles of treatment (approximately 12-18 weeks).
measure: Downstaging Rate
timeFrame: After 4-6 cycles of treatment (approximately 12-18 weeks).
measure: 2-Year Disease-Free Survival (DFS)
timeFrame: From the start of treatment to 2 years post-treatment.
measure: 2-Year Overall Survival (OS)
timeFrame: From the start of treatment to 2 years post-treatment.
measure: Adverse Events
timeFrame: From the start of treatment to the end of the study (up to approximately 24 months).
measure: Quality of Life (QoL)
timeFrame: Baseline, every 3 weeks during treatment, and every 12 weeks post-treatment, up to 24 months.
Other outcomes:
Locations:
city: Chengdu
country: China
facility: West China Hospital of Sichuan University
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
Study officials:
References: