HIPEC Combined With Sintilimab for Gastric Cancer With Peritoneal Metastasis

Study Overview
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Brief Summary
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To evaluate the Safety and Efficacy of HIPEC Combined With Sintilimab for Gastric Cancer Patients with Peritoneal Metastasis.

Detailed Description
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Peritoneal metastasis is the most common pattern of disease relapse and is attributed to the dismal prognosis of the gastric cancer. The National Comprehensive Cancer Network (NCCN) guidelines suggest that systemic chemotherapy is the first-line standard strategy, and chemotherapy combined with trastuzumab for patients with positive HER-2. HIPEC can significantly improve survival in peritoneal metastasis from gastric cancer. PD-1/PD-L1 antibody has shown promising outcomes for unresectable or metastatic solid tumors. The present study aimed to evaluate the safety and efficacy of HIPEC combined with Sintilimab (Tyvyt®) in gastric cancer patients with peritoneal metastasis.

Official Title
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A Phase II Study of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Combined With Sintilimab in Gastric Cancer With Peritoneal Metastasis

Conditions
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Gastric Cancer

Intervention / Treatment
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* Drug: HIPEC,anti-PD-1 antibody Sintilimab (Tyvyt®), Chemotherapy,Surgery


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Advanced gastric (gastroesophageal junction) adenocarcinoma confirmed by histology; Age 18-75 years, Male or Non pregnant female ECOG (Eastern Cooperative Oncology Group) : 0 1； Negative for HER-2 by IHC/FISH； Peritoneal metastasis is confirmed by laparoscopic exploration, and the PCI≤20； Untreated (e.g. radiotherapy, chemotherapy, target therapy and immunotherapy); Normal Bone marrow, liver and kidney function indices before the recruitment: Expected survival≥ 12 week Signed the Informed Consent Form, and blood and tissue samples can be obtained; Exclusion Criteria: Other distal metastases besides peritoneal metastases (e.g., liver, lung, pleural, brain, bone metastases, etc.); Previous systemic therapy for gastric cancer; Recurrent gastric cancer after surgery; Cardiopulmonary dysfunction; Immunosuppressive drugs(eg.Corticosteroids) were used within 14 days before treatment, eg.corticosteroids, There is any active autoimmune disease or a history of autoimmune disease (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism; subjects with vitiligo or asthma in childhood have been completely relieved, and those who do not need any intervention after adulthood can be included Asthma requiring medical intervention with bronchodilator was not included.) Allergy to the drugs in this protocol； Patients with other diseases not suitable for inclusion, such as immune deficiency, active tuberculosis, hepatitis B (non-active hepatitis B surface antigen (HBsAg) carriers, hepatitis B virus titer <500IU/ml after treatment and with normal liver function can be included), hepatitis C virus positive; A history of idiopathic pulmonary fibrosis, tissue pneumonia, drug pneumonia, idiopathic pneumonia, or r active pneumonia; Other patients who were considered unsuitable for inclusion by the researchers;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Gastric Cancer With Peritoneal Metastasis, HIPEC, Anti-PD-1 Antibody<br>Surgical exploration, if PCI≤20, then we perform this study. HIPEC: HIPEC is performed after laparoscopic exploration, Mitomycin 30mg/m2, d1, Docetaxel 40mg/m2, d3, Oxaliplatin 65mg/m2, d5 within a week after surgical exploration; Chemotherapy(SOX) and anti-PD-1 antibody Sintilimab (Tyvyt®) treatment followed (4 cycles): SOX regimen: Oxaliplatin: 130 mg/m^2, IV, d1; S-1, 40-60 mg/m^2 bid, po, day 1-14, every 3 weeks for a total of 4 cycles; Sintilimab (Tyvyt®) 200mg fixed dose every 3 weeks, for a total of 4 cycles. Surgery: Imaging and secondary surgical exploration, assess the patient's condition and consider whether perform the cytoreductive surgery (resection of primary tumors and metastases ). After the surgery, HIPEC for three cycles, Mitomycin 30mg/m2, d1, Docetaxel 40mg/m2, d3, Oxaliplatin 65mg/m2, d5 within a week after surgery; For inoperable patients, continue to use standard chemotherapy. After the surgery, continue to use standard adjuvant chemotherapy. | Drug: HIPEC,anti-PD-1 antibody Sintilimab (Tyvyt®), Chemotherapy,Surgery<br>* HIPEC: HIPEC is performed after laparoscopic exploration, Mitomycin 30mg/m2, d1, Docetaxel 40mg/m2, d3, Oxaliplatin 65mg/m2, d5 within a week after surgical exploration. Chemotherapy(SOX) and anti-PD-1 antibody Sintilimab (Tyvyt®) treatment followed (4 cycles): SOX regimen: Oxaliplatin: 130 mg/m^2, IV, d1; S-1, 40-60 mg/m^2 bid, po, day 1-14, every 3 weeks for a total of 4 cycles; Sintilimab (Tyvyt®) 200mg fixed dose every 3 weeks, for a total of 4 cycles. Surgery: Imaging and secondary surgical exploration, assess the patient's condition and consider whether perform the cytoreductive surgery (resection of primary tumors and metastases). For patients undergoing surgery, HIPEC for three cycles followed, Mitomycin 30mg/m2, d1, Docetaxel 40mg/m2, d3, Oxaliplatin 65mg/m2, d5 within a week after surgery; For inoperable patients, continue to use standard chemotherapy of guidelines recommend. After the surgery, continue to use standard adjuvant chemotherapy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| R0 resection | the rate of R0 resection | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival time | Overall survival time(OS) refers to the time of first use of the drug to the time of death. At the end of the study, if the subject is still alive, refer the known date of last survival of the subject as the date of censoring. | 2 years | 
| ORR | Objective response rate(ORR): ORR = (number of subjects with complete response (CR) + partial response (PR))/total number of subjects ×100%. Measurable lesion according to the RECISTv1.1 | 3 months | 
| Event-Free Survival | Defined as the interval between the first conversion therapy and the first recorded related events, including preoperative disease progression, postoperative disease recurrence, and death from any cause. | 2 years | 
| Relapse-Free Survival | Defined as postoperative the first recorded postoperative recurrence of disease or death from any cause | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD1, Gastric Cancer, Peritoneal Metastasis, HIPEC