HIPEC Combined With SOX and Sintilimab in the Treatment of Advanced Gastric Cancer With Peritoneal Metastasis

The Efficacy and Safety of Hyperthermic Intraperitoneal Chemotherapy （HIPEC）Combined With SOX and Sintilimab in the Treatment of Advanced Gastric Cancer With Peritoneal Metastasis: A Prospective, Single-arm, Phase II Clinical Study

The prognosis of patients with peritoneal metastasis from gastric cancer is extremely poor. Although chemotherapy combined with immunotherapy has achieved promising efficacy in the first-line treatment of advanced gastric cancer, patients with peritoneal metastasis benefit less from this regimen. Hyperthermic intraperitoneal chemotherapy (HIPEC) represents a novel treatment option, which maintains the high concentration of drugs in the abdominal cavity, and improve the anti-tumor efficacy of chemotherapy drugs through the thermo-thermal effect. The purpose of this study is to investigate the efficacy and safety of HIPEC and systemic chemotherapy combined with sintilimab in the first-line treatment of advanced gastric cancer and gastroesophageal junction adenocarcinoma with peritoneal metastasis.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Cancer; Peritoneal Metastases
• Intervention / Treatment: Drug: S-1, Oxaliplatin sintilimab HIPEC

Detailed Description

To determine the efficacy and safety of HIPEC and systemic chemotherapy combined with sintilimab in the first-line treatment of advanced gastric cancer with peritoneal metastasis, patients will receive SOX regimen chemotherapy combined with sintilimab, once every three weeks. In the first cycle, HIPEC will be administrated, and HIPEC or intraperitoneal chemotherapy will be administrated in the second to third cycles according to the patient's condition. Then, another 3-cycle SOX regimen of systemic chemotherapy will be administrated. After the end of 6 cycles, patients will receive maintain treatment with a combination of S-1 and sintilimab until disease progression or intolerable toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 69
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Hongfeng Gou, M.D; Phone Number: +8618980602292; Email: gouhongfeng@yeah.net
• Study Contact Backup: Name: Pengfei Zhang, M.D.; Phone Number: +8617828163584; Email: fly_121988@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18-75 years.
2. Unresectable gastric/gastroesophageal junction adenocarcinoma diagnosed with peritoneal metastasis through laparoscopic exploration and pathological or cytological examination;
3. No previous antitumor treatment.
4. Agree to provide blood/tissue specimens.
5. The expected survival is more than 3 months.
6. ECOG PS≤1.

7. Adequate organ function including the following:

   1. Total bilirubin ≤1.5 times the upper limit of normal (ULN);
   2. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤3×ULN;
   3. Alkaline phosphatase≤2.5×ULN (if the tumor invaded the liver, ≤3×ULN);
   4. Serum creatinine≤1.5×ULN;
   5. Serum amylase and lipase≤1.5×ULN;
   6. International standardized ratio (INR)/partial thromboplastin time (PTT)≤1.5×ULN;
   7. Platelet count ≥ 75,000 /mm3;
   8. Hemoglobin (Hb) ≥ 9 g/dL;
   9. Absolute neutrophil count (ANC) ≥ 1500/mm3;
8. Strict contraception.
9. Patients must be able to understand and be willing to sign the written informed consent form. A signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure.

Exclusion Criteria:

1. Undergoing other drug clinical trials or having participated in any drug clinical trials one month before enrollment.
2. Active autoimmune disease or history of refractory autoimmune disease.
3. Receiving corticosteroids (> 10mg/d prednisone or equivalent dose of steroids) or other systematic immunosuppression therapies within 14 days before enrollment, excluding the following therapies: steroid hormone replacement therapy (≤10mg/d); local steroid therapy; and short-term, prophylactic steroid therapy for preventing allergies or nausea and vomiting.

4. Active or clinically significant cardiac disease:

   1. Congestive heart failure > New York Heart Association (NYHA) class 2;
   2. Active coronary artery disease;
   3. Arrhythmias requiring treatment other than β-blockers or digoxin;
   4. Unstable angina (with angina symptoms at rest), new angina within 3 months before enrollment, or new myocardial infarction within 6 months before enrollment
5. Gastrointestinal perforation, obstruction, or uncontrollable diarrhea in the 6 months prior to enrollment;
6. Other tumors that have not been treated or exist at the same time, except carcinoma in situ of the cervix, treated basal cell carcinoma or superficial bladder tumor. If the tumor was cured and no evidence of disease was found for more than 3 years, the patient can be enrolled. All other tumors must be treated at least 3 years before enrollment.
7. Patients with pheochromocytoma.
8. Patients with a history of HIV infection or active hepatitis B/C.
9. Ongoing > level 2 infection.
10. Symptomatic brain metastasis or meningioma.
11. Unhealed wounds, ulcers or fractures.
12. Renal failure patients requiring blood or peritoneal dialysis.
13. Epileptic that needs medication.
14. History of organ transplantation (including corneal transplantation).
15. Allergic to research drugs or similar drugs, or suspected allergies.
16. Pregnant or lactating women.
17. Medical, psychological or social conditions can affect the recruitment of patients and evaluation of study results.
18. Other antitumor therapy (chemotherapy, radiotherapy, surgery, immunotherapy, biotherapy, chemoembolization) other than investigator drugs. Palliative external irradiation for non-target lesions is allowed.
19. Previously used similar chemotherapy drugs or immune checkpoint inhibitors;
20. Major surgery 4 weeks before recruitment, open biopsy or major trauma surgery (excluding biliary stents, or percutaneous biliary drainage).
21. Treatment with antitumor Chinese herbal medicine.
22. Vaccination history 4 weeks prior to enrollment
23. The investigator believes that patients who are not suitable for the study.

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: SOX+sintilimab+HIPEC; Patient will receive SOX regimen (oxaliplatin 100mg/m2, d1, S-1 BSA<1.25m2 40mg, twice a day; 1.25m2 ≤ BSA < 1.5m2 50mg, twice a day; BSA ≥ 1.5m2 60mg, twice a day; d1-14) chemotherapy combined with sintilimab (200mg, d1), once every three weeks. In the first cycle, HIPEC (paclitaxel 80 mg/m2, d1-d3) will be administrated, and HIPEC or intraperitoneal chemotherapy (paclitaxel 80 mg/m2, d1) will be administrated in the second and third cycles according to the patient's condition. Then, another 3-cycle SOX regimen of systemic chemotherapy. After the end of 6 cycles, maintain treatment with a combination of S-1 and sintilimab until disease progression or intolerable toxicity.

Drug: S-1, Oxaliplatin sintilimab HIPEC; Exploratory laparoscopy or laparotomy; SOX regimen (oxaliplatin 100mg/m2, d1, S-1 BSA<1.25m2 40mg, twice a day; 1.25m2 ≤ BSA < 1.5m2 50mg, twice a day; BSA ≥ 1.5m2 60mg, twice a day; d1-14) chemotherapy combined with sintilimab (200mg, d1), once every three weeks.; In the first cycle, HIPEC (paclitaxel 80 mg/m2, d1-d3) will be administrated,; In the second and third cycles, HIPEC or intraperitoneal chemotherapy (paclitaxel 80 mg/m2, d1) will be administrated according to the patient's condition.; Another 3-cycle SOX regimen of systemic chemotherapy.; After the end of 6 cycles, maintain treatment with a combination of S-1 and sintilimab until disease progression or intolerable toxicity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival	Overall survival (OS) is defined as the time from randomization to death	every 3 month postoperation up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective Response Rate	every 3 month postoperation up to 24 months
DCR	disease control rate	every 3 month postoperation up to 24 months
Progression-free survival	Progression-free survival (PFS) is defined as the time from randomization to diesea progression	every 3 month postoperation up to 24 months
Safety and Tolerability	Treatment-related adverse events as assessed by CTCAE v4.0	every 3 month postoperation up to 24 months

Collaborators and Investigators

• Sponsor: Sichuan University
• Investigators: Principal Investigator: Kun Yang, M.D., West China Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): February 20, 2024
• Primary Completion (Estimated): May 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: January 1, 2024
• First Submitted That Met QC Criteria: January 18, 2024
• First Posted (Estimated): January 19, 2024

Study Record Updates

• Last Update Posted (Estimated): January 19, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: gastric cancer; HIPEC; first-line; 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; Antineoplastic Agents; Oxaliplatin
• Other Study ID Numbers: WCH-2023-1784

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