Treatment-naïve HER2-negative unresectable advanced gastric cancer
Conditions
Interventions
Experimental group:Combination of varying doses of stiripentol with anti-PD-1 antibody and the XELOX regimen(Oxaliplatin 130 mg/m2 IV on day 1 + Capecitabine 1000 mg/m).
Sponsors
The Seventh Affiliated Hospital of Sun Yat-sen University (Shenzhen)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1.Sex: Male or female; 2.Age: 18 years or older at the time of informed consent; 3.Disease Status: Patients with unresectable advanced gastric cancer (including 1. Unresectable locally advanced gastric cancer with tumor invasion and adhesion to the root of the mesentery, tumor encasement of major vessels, or metastatic lymph nodes encasing major vessels such as the portal vein or aorta; 2. Metastatic advanced gastric cancer), histologically confirmed adenocarcinoma, HER2-negative, and who have not received any prior anti-tumor therapy; 4.Measurable Lesions: Presence of at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 on CT or MRI scan performed within 28 days prior to screening enrollment; 5.Tumor Tissue: Ability to provide a tumor tissue sample (archived or from a fresh biopsy) for PD-L1 expression analysis. For patients unable to undergo a new biopsy, an archival sample is an acceptable alternative; 6.ECOG Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 7.Life Expectancy: Life expectancy of at least 3 months; 8.Adequate Organ Function: Have the following latest laboratory data meeting the criteria below within 7 days prior to screening enrollment. If the laboratory test date at randomization is not within 7 days before the first dose of the study drug, the test must be repeated within 7 days before the first dose of the study drug, and the latest laboratory data before the first dose of the study drug must be confirmed to meet the following criteria. Note that laboratory data will be considered invalid if the patient has received granulocyte colony-stimulating factor (G-CSF) or blood transfusion within 14 days prior to the test. White Blood Cell (WBC) count >=3000/mm^3, Absolute Neutrophil Count (ANC) >= 1500/mm^3 Platelet count >= 80000/mm^3 Hemoglobin >= 8.0 g/dL Aspartate Aminotransferase (AST [GOT]) and Alanine Aminotransferase (ALT [GPT]) 60 mL/min #1: Note that if SOX therapy is selected in Part 2, the criterion for initiating SOX therapy is =12 consecutive months of amenorrhea without an alternative medical cause. Women using oral contraceptives or mechanical contraception such as intrauterine devices and barrier methods are considered to have childbearing potential. 10.Contraception for Men: Male patients must agree to use contraception#3 starting from the initiation of study treatment until at least 7 months after the last dose of study drug or combination chemotherapy, whichever is later. #3: Patients must agree to use at least two
Exclusion criteria
Exclusion criteria: 1.Known lesions with signs of active bleeding; 2.Gastric cardia or pyloric obstruction affecting food intake and gastric emptying, or causing difficulty swallowing whole tablets; 3.Diagnosis of HER2-positive gastric or gastroesophageal junction adenocarcinoma (G/GEJ AC); 4.Tumor tissue testing (immunohistochemistry or molecular testing) indicates deficient mismatch repair (dMMR) or microsatellite instability-high (MSI-H) status; 5.Prior systemic therapy for advanced or metastatic G/GEJ AC; 6.Cumulative cisplatin dose = 300 mg/m² from prior (neo)adjuvant therapy; 7.Peripheral neuropathy not resolved to Grade 1 or better after prior therapy; 8.Known complete deficiency of dihydropyrimidine dehydrogenase (DPD) enzyme (or history of Grade >=3 mucosal toxicity with prior fluoropyrimidine treatment); 9.Known hypersensitivity (history of Grade >=3 allergic reaction) to any monoclonal antibody or to any component of the chemotherapy agents (capecitabine and/or oxaliplatin); 10.Prior treatment with any anti-programmed cell death protein 1 (anti-PD-1), anti-programmed death-ligand 1 (anti-PD-L1), anti-programmed death-ligand 2 (anti-PD-L2), anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways; 11.History of neurological diseases such as Parkinson's disease that could cause tremors or ataxia; 12.History of psychiatric illness; 13.Inability to provide informed consent due to specific reasons (e.g., concurrent dementia); 14.Participation in another interventional clinical study, unless it is an observational (non-interventional) study or the follow-up phase of an interventional study; 15.Systemic treatment with traditional Chinese medicine for cancer indications or immunomodulators (including thymosin, interferons, interleukins) within 2 weeks prior to the first dose of study drug; 16.Treatment with immunosuppressive medication within 4 weeks prior to the first dose of study drug. Exceptions include intranasal, inhaled, or topical corticosteroids, or systemic corticosteroids at physiological doses (<=10 mg/day prednisone or equivalent), or corticosteroids used for prophylaxis of contrast agent allergy; 17.Receipt of live attenuated vaccine within 4 weeks prior to the first dose of study drug, or plans to receive such vaccine during the study. Note: Seasonal inactivated influenza vaccines are allowed; live attenuated influenza vaccines are not; 18.Major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the first dose of study drug, or planned major surgery during the trial; laparoscopic examination within 2 weeks prior to the first dose of study drug; 19.Toxicity related to prior anti-tumor therapy (excluding alopecia, clinically non-significant events, or asymptomatic laboratory abnormalities) that has not recovered to Grade 0 or 1 as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 prior to the first dose of study drug; 20.Known symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with treated brain metastases are eligible if stable (no evidence of progression on imaging for at least 4 weeks prior to the first dose, with no new or enlarging metastases) and off systemic corticosteroids for at least 14 days prior to the first dose. Patients with carcinomatous meningitis are excluded regardless of clinical stab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival;Pharmacokinetics;Progress-free survival;Disease control rate;Duration of relief; | — |
Countries
China
Contacts
Public ContactZhang Changhua; Zhao Yi; Chen Hong
The Seventh Affiliated Hospital of Sun Yat-sen University (Shenzhen)
Outcome results
None listed