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

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.

Study Overview

• Status: Recruiting
• Conditions: Peritoneal Metastases; Gastric Cancer Stage IV
• Intervention / Treatment: Drug: sintilimab, paclitaxel and S-1

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhongyin Yang, PhD; Phone Number: 671304 8621-64370045; Email: jeffreyyong@163.com
• Study Contact Backup: Name: Min Shi, PhD; Phone Number: 8621-64370045; Email: shimin0412005@126.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200025
      • Recruiting
      • Ruijin Hospital Shanghai Jiao Tong University School of Medicine
      • Contact: Zhongyin Yang, PhD; Phone Number: 671304 +862164370045; Email: jeffreyyong@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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: Intraperitoneal; 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.	Drug: 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 with one week rest.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
1-year survival rate	12 months

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 20, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: December 25, 2021
• First Submitted That Met QC Criteria: January 10, 2022
• First Posted (Actual): January 24, 2022

Study Record Updates

• Last Update Posted (Actual): January 24, 2022
• Last Update Submitted That Met QC Criteria: January 10, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Gastric cancer; Chemotherapy; Paclitaxel; Sintilimab; Peritoneal metastasis
• 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: DRAGON-09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

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