Combination treatment for advanced gastric cancer with malignant ascites

Sintilimab in Combination With Systemic S-1/Oxaliplatin Chemotherapy With Nab-paclitaxel Intraperitoneal Infusion as First-line Treatment for Advanced Gastric/Gastroesophageal Junction (GC/GEJ) Adenocarcinoma With Malignant Ascites: Open-label, Single-arm, Phase II Trial

This study is testing a new combination treatment for people with advanced stomach cancer and fluid buildup in the abdomen to see if it helps them feel better and improve their health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 35 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, Sintilimab
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT06046963 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the efficacy and safety of a combination treatment involving Sintilimab, S-1, oxaliplatin, and nab-paclitaxel delivered via intraperitoneal infusion for patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma accompanied by malignant ascites. It is a single-arm, open-label, phase II trial conducted in China, aiming to recruit 35 patients who have not received prior systemic treatment. The study will also explore potential biomarkers by collecting various biological samples before and after treatment to assess their predictive value for treatment efficacy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with unresectable advanced gastric or gastroesophageal junction adenocarcinoma and moderate to high volume of malignant ascites.

Not a fit: Patients with HER2 positive tumors or those who have received prior systemic treatment for their cancer may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new first-line therapeutic option for patients with advanced gastric cancer and malignant ascites.

How similar studies have performed: While the combination of immunotherapy and chemotherapy is being explored in various contexts, this specific approach for gastric cancer with malignant ascites is relatively novel and has not been extensively tested.

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.

Where this trial is running

Hangzhou, Zhejiang

• Zhejiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Jieer Ying, Dr — Zhejiang Cancer Hospital
• Study coordinator: Jiaojiao Ni, Dr

Conditions Gastric Cancer; Peritoneal Metastases; Ascites, Malignant; Malignant ascites