Sintilimab in Combination With S-1/Oxaliplatin With Nab-paclitaxel Intraperitoneal Infusion for Untreated 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

To evaluate the efficacy and safety of Sintilimab in Combination With S-1/oxaliplatin With nab-paclitaxel intraperitoneal infusion as First-line Treatment for advanced gastric/gastroesophageal junction (GC/GEJ) adenocarcinoma with malignant ascites

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Peritoneal Metastases; Ascites, Malignant
• Intervention / Treatment: Drug: Sintilimab in Combination With S-1/oxaliplatin With nab-paclitaxel intraperitoneal infusion; Other: Blood samples, tumor biopsy specimens, ascites, and feces samples will be collected

Detailed Description

Peritoneal metastasis(PM) is common in advanced gastric cancer and associated with a poor prognosis. The efficacy of immunotherapy combined with chemotherapy in gastric cancer with PM is still not clear, and there is a lack of biomarkers for efficacy prediction. It is a single arm, open-label, phase II cinical trial conducted in China and plans to recruit 35 patients who were primarily diagnosed with unresectable or metastatic gastric/gastroesophageal junction (GC/GEJ) adenocarcinoma with malignant ascites who have not received previous systemic treatment. Patients plan to receive sintilimab in combination with S-1/oxaliplatin with nab-paclitaxel intraperitoneal infusion as first-line treatment. The purpose of this study is to evaluate the efficacy and safety of sintilimab in combination with S-1/oxaliplatin with nab-paclitaxel intraperitoneal infusion for untreated advanced GC/GEJ adenocarcinoma with malignant ascites. To explore the potential biomarkers, tumor tissue paraffin section, peripheral blood, ascites, and feces before and after treatment will be collected and investigated by multiomics sequencing.

• Study Type: Interventional
• Enrollment (Estimated): 35
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jieer Ying, Dr; Phone Number: 13858195803; Email: jieerying@aliyun.com
• Study Contact Backup: Name: Jiaojiao Ni, Dr; Phone Number: 15088667597; Email: 3140102210@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Recruiting
      • Zhejiang Cancer Hospital
      • Contact: Jieer Ying, Doctor; Phone Number: 13858195803; Email: hzyingjieer@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Immunotherapy combined with intravenous and intraperitoneal chemotherapy; advanced gastric/gastroesophageal junction (GC/GEJ) adenocarcinoma patients with malignant ascites who have agreed to receive Immunotherapy combined with intravenous and intraperitoneal chemotherapy

Drug: Sintilimab in Combination With S-1/oxaliplatin With nab-paclitaxel intraperitoneal infusion; Sintilimab: 200 mg, intravenous infusion, d1, q3w; Nab-paclitaxel: 100 mg/m2 intraperitoneal infusion, d1, q3w; S-1: calculated based on body surface area Dosage, twice a day, orally, d1-d14, q3w; Oxaliplatin: 130 mg/m2, intravenous infusion, d1, q3w; The dosage can be adjusted according to the protocol according to the adverse reactions of subjects. Subjects wil continue to take medication until completion of the prescribed course of treatment, disease progression, toxicity intolerance, withdrawal of informed Consent Form, or termination in the investigator's judgment.; Other: Blood samples, tumor biopsy specimens, ascites, and feces samples will be collected; Blood samples, tumor biopsy specimens, ascites, and feces samples will be collected at diferent time points (if feasible, according to the samples taken in the standard practice): at Baseline; After 1-2 cycles of treatment; at the time of the progression or recurrence, if applicable.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ascites objective response rate (ORR)	The ascites objective response rate (ORR) was calculated as a summed ratio of patients with disappeared and decreased ascites to the total number of patients.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is calculated from diagnosis to death or last follow-up time	1 year
Progress free survival (PFS)	PFS is defined as the time from the date of treatment to the first date of disease	1 year
12 months os rate	The definition of 12-months OS rate is the percentage of patients who had NOT has an event before or at 12 months	1 year
Obiective response rate of Solid tumor lesion (if exists)	Number of participants with partial response or complete response treating by anloitnib according to RESIST criteria v1.1	1 year
Safety assessment	Number and percentage of participants with Adverse Events (any Grade and Grade 3/4)	1 year
Changes of ascite cell subsets in patients	Changes in ascites cell subsets in patients before and after treatment. Differences in the proportion of subpopulations and gene expression levels of ascites cells between responders and non-responders by single-cell sequencing.	1 year

Collaborators and Investigators

• Sponsor: Zhejiang Cancer Hospital
• Investigators: Principal Investigator: Jieer Ying, Dr, Zhejiang Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2023
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: September 10, 2023
• First Submitted That Met QC Criteria: September 18, 2023
• First Posted (Actual): September 21, 2023

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 18, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Gastric Cancer; Malignant ascites; Peritoneal Metastases
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Neoplastic Processes; Stomach Neoplasms; Neoplasm Metastasis; Ascites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Oxaliplatin
• Other Study ID Numbers: IRB-2023-704

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No