Efficacy and Safety of Sintilimab Combined Intraperitoneal and Intravenous Paclitaxel Plus Oral S-1 in Gastric Cancer Patients With Peritoneal Metastasis

Phase 2

• Conditions: Gastric Cancer Stage IV; Peritoneal Metastases
• Interventions: Drug: sintilimab, paclitaxel and S-1

• Registration Number: NCT05204173
• Lead Sponsor: Ruijin Hospital

Brief Summary

In this phase 2 study, we combined sintilimab, paclitaxel and S-1 as regimen to treat gastric cancer patients with peritoneal metastasis. We are aim to estimate the efficacy and safety of this regimen in the phase 2 study.

Detailed Description

Gastric cancer patients enrolled in this a phase 2 study received sintilimab (200mg intravenously on day 1), paclitaxel (PTX) (20 mg/m2 intraperitoneally and 50 mg/m2 intravenously on days 1 and 8) plus oral S-1 (80 mg/m2 for 14 consecutive days) every 3 weeks. The primary endpoint is 1-year survival rate. Secondary endpoints are adverse events, R0 resection rate, 3-year overall survival (OS), and 3-year progressive free survival. Adverse events are monitored and graded according to the Common Terminology Criteria for Adverse Events version 4.0.

Study Timeline

• Study Start: 2021-05-20
• Study First Submitted: 2021-12-25
• Status Verified: 2022-01
• Study First Submitted QC: 2022-01-10
• Last Update Submitted: 2022-01-10
• Study First Posted: 2022-01-24
• Last Update Posted: 2022-01-24
• Primary Completion: 2023-12
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Histologically confirmed gastric adenocarcinoma;
2. Peritoneal metastases from gastric cancer requiring definitive diagnosis by laparoscopy, and without gastric outflow tract obstruction and intestinal obstruction;
3. Written (signed) informed consent;
4. Age ≥ 18 years at registration;
5. Eastern Cooperative Oncology Group (ECOG) score ≤ 2;
6. Expected life expectancy > 3 months;
7. Adequate bone marrow, liver, and renal functions. absolute neutrophil count of ≥1.5×109/L; absolute neutrophil count of ≥1.5×109/L; platelet count of ≥100×109/L; hemoglobin ≥90g/L; bilirubin of <1.5×upper limit of normal [ULN]; alanine aminotransferase and aspartate aminotransferase of <2.5×ULN; serum creatinine of ≤1.5×ULN; creatinine clearance of >50 mL/min; TSH ≤1×ULN (if abnormal, T3 and T4 levels should be inspected at the same time, if T3 and T4 levels are normal, they can be included in the group); APTT ≤1.5×ULN and INR ≤1.5×ULN; myocardial enzymogram ≤1×ULN.

Exclusion Criteria

1. Confirmed of evidence of distant metastasis other than peritoneal metastasis (e.g.liver metastasis, lung metastasis, para-aortic lymph node metastasis, etc.);
2. During pregnancy, within 28 days of post parturition, or during lactation;
3. Synchronous or metachronous (within 5 years) malignancies.
4. Severe mental disease, uncontrolled epilepsy, or central nervous system disease;
5. Clinically severe (i.e. active) heart disease, such as symptomatic coronary heart disease, New York Heart Association (NYHA) class II or more severe congestive heart failure or arrhythmia requiring drug intervention, or a history of myocardial infarction in the last 12 months;
6. Upper gastrointestinal obstruction or abnormal physiological function or malabsorption syndrome may affect S-1 absorbers;
7. Known peripheral neuropathy (> NCI-CTC AE 1). However, patients with only disappearance of deep tendon reflex (DTR) need not be excluded;
8. Patients on steroid or immunosuppressant treatment after organ transplant;
9. Patients with severe uncontrolled recurrent infections or other severe uncontrolled concomitant disease;
10. Moderate or severe renal damage [creatinine clearance ≤ 50 ml/min], or serum creatinine > upper limit of normal (ULN), 115 μmol/L;
11. Known dihydropyrimidine dehydrogenase (DPD) deficiency;
12. Anaphylaxis to paclitaxel or any research drug ingredient.
13. Active autoimmune disease or history of refractory autoimmune disease; Subjects with hypothyroidism requiring only hormone replacement therapy and skin diseases without systemic treatment (such as vitiligo, psoriasis or alopecia) can be selected;
14. HIV antibody positive, active hepatitis B or C (hepatitis B: HBsAg positive and HBV DNA ≥10 copies/ml; hepatitis C: HCV antibody and HCV-RNA positive, requiring antiviral treatment at the same time);
15. Steroid or other systemic immunosuppressive therapy was used 14 days before admission, excluding local or physiological doses of systemic glucocorticoids (eg. no more than 10mg/day of prednisone or other glucocorticoids of equivalent dose) by nasal spray, inhalation or other routes, or hormones used to prevent allergy of contrast agents;
16. Uncontrolled arrhythmia and myocardial infarction within 12 months before admission or active tuberculosis.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intraperitoneal	sintilimab, paclitaxel and S-1	Sintilimab 200mg intravenous (IV) infusion on day 1, PTX 50 mg/m2 IV and PTX 20 mg/m2 intraperitoneal infusion on Days 1 and 8 plus oral S-1 80 mg/m2 for 14 consecutive days every 3 weeks.

Primary Outcome Measures

Name	Time	Method
1-year survival rate	12 months

Secondary Outcome Measures

Name	Time	Method
Number of participants experiencing clinical and laboratory adverse events (AEs)	24 months
3-year progressive free survival (PFS)	36 months
R0 resection rate	24 months
3-year overall survival (OS)	36 months

Trial Locations

Locations (1)

Ruijin Hospital Shanghai Jiao Tong University School of Medicine; 🇨🇳 Shanghai, Shanghai, China