Sintilimab in Combination With S-1/Oxaliplatin With Nab-paclitaxel Intraperitoneal Infusion for Untreated Advanced Gastric Cancer With Malignant Ascites

Launched by ZHEJIANG CANCER HOSPITAL · Sep 18, 2023

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment approach for patients with untreated advanced gastric cancer (stomach cancer) that has spread to the abdomen and is causing fluid buildup known as malignant ascites. The study is testing a combination of three medications: Sintilimab, S-1, and oxaliplatin, along with nab-paclitaxel delivered directly into the abdominal cavity. The goal is to see how effective and safe this combination is for patients with this specific type of cancer.

To participate in this trial, patients need to be between 18 and 75 years old and have a confirmed diagnosis of advanced gastric or gastroesophageal junction adenocarcinoma that cannot be surgically removed. They should also have a certain amount of fluid buildup in the abdomen and meet other health criteria. Participants can expect regular check-ups and monitoring to assess their response to the treatment and any side effects. This trial is currently recruiting patients, and it’s important to note that those with specific other health conditions or previous treatments may not be eligible. If you think you might qualify or want to learn more, discussing this with your healthcare provider is a good first step.

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Eligibility criteria

• Inclusion Criteria:
• • 1. Have fully understood the research and voluntarily signed the informed consent;
• • 2. Gastric adenocarcinoma or gastroesophageal junction adenocarcinoma confirmed by pathology, and unresectable advanced or metastatic disease;
• • 3. HER2 negative, mismatch repair-proficient (pMMR);
• • 4. Moderate or above volume of ascites at baseline;
• • 5. Peritoneal metastasis confirmed by ascites cytology or laparoscopy;
• • 6. Aged from 18 to 75 years old, regardless of gender;
• • 7. Within 7 days before the first administration of the study drug, the ECOG score is 0-2;
• • 8. Expected survival period ≥ 3 months;
• 9. Adequate organ function:
• Routine Blood Test: (no blood transfusion, no use of granulocyte colony-stimulating factor \[G-CSF\], no drug correction within 14 days prior to screening):
• • 1. Neutrophils ≥ 1.5×109/L;
• • 2. Platelets ≥ 75×109/L;
• • 3. Hemoglobin ≥ 90g/L;
• Biochemical examination: (No albumin infusion within 14 days before screening):
• • 4. Serum creatinine ≤ 1.5 × upper limit of normal ULN, or creatinine clearance \> 50 mL/min;
• • 5. Serum total bilirubin ≤ 1.5×ULN (patients with Gilbert syndrome are allowed to have total bilirubin ≤ 3×ULN);
• • 6. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5×ULN; for patients with liver metastasis, ALT and AST ≤ 5×ULN;
• Coagulation:
• • 7. International normalized ratio (INR) ≤ 2.3 or prothrombin time (PT) exceeding the normal control range ≤ 6 seconds;
• • 8. Urinary protein \< 2+ (if urinary protein ≥ 2+, 24-hour (h) urine protein quantification can be performed, and 24-h urine protein quantification \< 1.0 g can be included in the study)
• Cardiac Function:
• • 9. New York Heart Association (NYHA) classification \<3;
• • 10. Left ventricular ejection fraction ≥ 50%;
• • 10. Within 28 days before enrollment, women of childbearing age must confirm that the serum pregnancy test is negative and agree to use effective contraception during the use of the study drug and within 60 days after the last dose.
• • 11. Patients must have an appropriate nutritional status: BMI ≥ 18 kg/m2, body weight ≥ 40 kg, and serum albumin ≥ 28 g/L.
• Exclusion Criteria:
• • 1. HER2-positive (IHC3+ or IHC2+ and FISH-positive at the same time) or dMMR/MSI-H;
• • 2. Previously received systemic therapy for advanced unresectable or metastatic GC/GEJ adenocarcinoma. Patients can previously receive neoadjuvant therapy or adjuvant therapy, as long as it ends at least 6 months before this diagnosis without progress;
• • 3. Previously received immune checkpoint inhibitors (such as anti-PD-1 antibody, anti-PD-L1 antibody, anti-CTLA-4 antibody, etc.), immune checkpoint agonists, immune cell therapy and other immunotherapy.
• • 4. Previously received intraperitoneal chemotherapy, including hyperthermic intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC), intraperitoneal chemotherapy, etc.
• • 5. Other active malignant tumors other than GC/GEJ adenocarcinoma within 5 years or at the same time. Localized tumors that have been cured can be enrolled, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, carcinoma in situ of the breast, etc.;
• • 6. Uncontrolled or moderate and above pleural effusion, pericardial effusion;
• • 7. Hemorrhagic events that require blood transfusion, invasive intervention or hospitalization occurred within 3 months before the first administration, or currently have bleeding symptoms and require intervention (such as hemoptysis, hematuria, bloody stool);
• • 8. Thrombosis or embolism events occurred within 6 months before the start of study treatment, such as cerebrovascular accidents (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc.;
• • 9. Received major surgical treatment (except for diagnosis) within 4 weeks before the start of study treatment or expected major surgical treatment during the study period;
• • 10. Inability to swallow tablets, malabsorption syndrome, complete intestinal obstruction and other conditions affecting gastrointestinal absorption;
• • 11. There have been or are currently central nervous system metastases;
• • 12. Active autoimmune disease or history of autoimmune disease and possible relapse;
• • 13. Using immunosuppressant or systemic hormone therapy within 14 days before starting the study treatment to achieve the purpose of immunosuppression;
• • 14. Patients with congenital or acquired immune deficiency (such as HIV infection);
• • 15. Received attenuated live vaccine treatment within 28 days before starting the study treatment, or need to receive such vaccine during the expected treatment or within 60 days after the last dose;
• • 16. Received anti-tumor cytotoxic drug therapy within 2 weeks before the first administration; or received biological drug therapy, immunotherapy within 4 weeks before the first administration; or other study drug therapy;
• • 17. There are currently uncontrolled comorbidities, such as severe hypertension, decompensated cirrhosis, nephrotic syndrome, angina pectoris, severe arrhythmia, interstitial lung disease, uncontrolled metabolic disorders, severe active peptic ulcer disease or gastritis, severe bleeding tendency or coagulation disorder;
• • 18. The toxicity of previous anti-tumor therapy has not recovered to CTCAE 0-1 grade;
• • 19. Suffering from active tuberculosis (TB) and receiving anti-tuberculosis treatment;
• • 20. Patients with active hepatitis B or C (positive HBsAg and positive HBV DNA copy number; positive HBcAb);
• • 21. Pregnant or lactating women.