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

Peritoneal Metastases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05204173
• Other study ID #: DRAGON-09
• Status: Recruiting
• Phase: Phase 2
• Start date: May 20, 2021
• Est. completion date: December 2023

Study information

• Verified date: January 2022
• Source: Ruijin Hospital
• Contact: Zhongyin Yang, PhD
• Phone: 8621-64370045
• Email: jeffreyyong[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Gastric Cancer Stage IV
• Neoplasm Metastasis
• Neoplasms, Second Primary
• Peritoneal Metastases
• Stomach Neoplasms

Intervention

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.

Locations

Country	Name	City	State
China	Ruijin Hospital Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Ruijin Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1-year survival rate		12 months
Secondary	Number of participants experiencing clinical and laboratory adverse events (AEs)		24 months
Secondary	R0 resection rate		24 months
Secondary	3-year overall survival (OS)		36 months
Secondary	3-year progressive free survival (PFS)		36 months