HIPEC Priming Followed by Serplulimab Plus SOX/XELOX in Locally Advanced Gastric Cancer

NCT07621484 | Not Yet Recruiting Phase 2

• 1 other identifier: HIPEC-PRIME01
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

Patients with locally advanced gastric cancer (LAGC), particularly those with serosal invasion, remain at high risk of peritoneal recurrence despite standard perioperative treatment. Hyperthermic intraperitoneal chemotherapy (HIPEC) may eradicate free intraperitoneal tumor cells and microscopic peritoneal disease while potentially enhancing systemic anti-tumor immune activation. This is a prospective, single-center, single-arm exploratory study evaluating a HIPEC priming strategy followed by serplulimab-based neoadjuvant therapy in patients with locally advanced gastric cancer (cT3-4aN+M0). Eligible patients will undergo diagnostic laparoscopy confirming no visible peritoneal metastasis (P0) and negative peritoneal cytology (CY0), followed by docetaxel-based HIPEC. After recovery from HIPEC, patients will initially receive one cycle of serplulimab combined with fluoropyrimidine monotherapy (S-1 or capecitabine), followed by subsequent cycles of serplulimab combined with SOX/XELOX chemotherapy prior to radical gastrectomy. The primary endpoints are pathological complete response (pCR) rate and major pathological response (MPR) rate. Secondary endpoints include R0 resection rate, objective response rate (ORR), peritoneal recurrence-free survival (PRFS), overall survival (OS), and safety.

Conditions

Locally Advanced Gastric Cancer; Gastric Adenocarcinoma; Gastroesophageal Junction Adenocarcinoma

Keywords

Locally Advanced Gastric Cancer; HIPEC; Hyperthermic Intraperitoneal Chemotherapy; Peritoneal Recurrence

Outcome Measures

Primary Outcomes (2)

• Pathological Complete Response (pCR) Rate

  Proportion of patients achieving pathological complete response, defined as the absence of residual viable tumor cells in both the primary tumor and regional lymph nodes after neoadjuvant treatment and radical gastrectomy.

  At the time of surgery

• Major Pathological Response (MPR) Rate

  Proportion of patients achieving major pathological response, defined as ≤10% residual viable tumor cells in the resected primary tumor specimen following neoadjuvant treatment.

  At the time of surgery

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Perioperative

• R0 Resection Rate

  At surgery

• Peritoneal Recurrence-Free Survival (PRFS)

  Up to 3 years after surgery

• Overall Survival (OS)

  Up to 3 years

• Incidence of Treatment-Related Adverse Events

  From the date of informed consent signing until the end of the safety follow-up period (30 days after the last dose of study treatment)

Study Arms (1)

Experimental

EXPERIMENTAL

Participants will undergo diagnostic laparoscopy with peritoneal lavage cytology followed by docetaxel-based hyperthermic intraperitoneal chemotherapy (HIPEC). After recovery from HIPEC, patients will receive one induction cycle of serplulimab combined with fluoropyrimidine monotherapy (S-1 or capecitabine), followed by subsequent cycles of serplulimab combined with SOX/XELOX neoadjuvant chemotherapy prior to radical gastrectomy with D2 lymphadenectomy

Procedure: Hyperthermic Intraperitoneal Chemotherapy; Drug: Serplulimab; Drug: S-1; Drug: Capecitabine; Drug: Oxaliplatin; Procedure: Radical Gastrectomy

Interventions

Hyperthermic Intraperitoneal Chemotherapy PROCEDURE

Docetaxel-based hyperthermic intraperitoneal chemotherapy administered after diagnostic laparoscopy in patients with P0/CY0 locally advanced gastric cancer

Experimental

Serplulimab DRUG

Serplulimab administered intravenously every 3 weeks as part of neoadjuvant treatment

Experimental

S-1 DRUG

Oral S-1 administered during neoadjuvant treatment.

Experimental

Capecitabine DRUG

Oral capecitabine administered during neoadjuvant treatment.

Experimental

Oxaliplatin DRUG

Intravenous oxaliplatin administered as part of SOX/XELOX neoadjuvant chemotherapy.

Experimental

Radical Gastrectomy PROCEDURE

Standard radical gastrectomy with D2 lymphadenectomy performed after completion of neoadjuvant therapy.

Experimental

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years (inclusive); gender unrestricted.
• Histologically confirmed gastric or gastroesophageal junction adenocarcinoma via endoscopic biopsy.
• Clinical stage cT3-4a (imaging evidence of tumor invasion into or penetration through the serosa), any N (lymph node positive), M0 (no distant organ metastasis), based on the 8th Edition of the AJCC Staging Manual.
• Diagnostic laparoscopy confirms the absence of macroscopic peritoneal metastasis (P0) and negative peritoneal lavage cytology (CY0).
• Adequate cardiac function, rendering the patient eligible for curative-intent resection. If clinically indicated, patients with underlying ischemic heart disease, valvular heart disease, or other severe cardiac conditions must undergo a preoperative cardiac evaluation by a cardiologist.
• ECOG Performance Status (PS) score of 0 or 1 within 7 days prior to enrollment.
• Anticipated survival time of ≥ 6 months.
• Hepatitis B surface antigen (HBsAg) negative (-) and Hepatitis B core antibody (HBcAb) negative (-). If HBsAg is positive (+) or HBcAb is positive (+), the Hepatitis B virus DNA (HBV-DNA) level must be \< 1000 copies/mL, \< 200 IU/mL, or below the upper limit of normal (ULN) at the study center to be eligible for enrollment.
• HCV antibody negative (-).
• Major organ function is normal, defined as meeting the following criteria (having not received transfusions of blood products, albumin, recombinant human thrombopoietin, or colony-stimulating factors \[CSF\] within 14 days prior to randomization):
• Hematologic System Absolute Neutrophil Count (ANC) ≥ 1.5×10⁹/L Platelets (PLT) ≥ 100×10⁹/L Hemoglobin (Hb) ≥ 90 g/L Liver Function Total Bilirubin (TBIL) ≤ 1.5×Upper Limit of Normal (ULN) Alanine Aminotransferase (ALT) ≤ 2.5×ULN; ≤ 5.0×ULN for patients with liver metastases Aspartate Aminotransferase (AST) ≤ 2.5×ULN; ≤ 5.0×ULN for patients with liver metastases Alkaline Phosphatase (ALP) ≤ 2.5×ULN; ≤ 5.0×ULN for patients with liver and/or bone metastases Albumin ≥ 25 g/L Renal Function Creatinine Clearance (CrCl) ≥ 50 mL/min (calculated using the Cockcroft-Gault formula) Coagulation Function Activated Partial Thromboplastin Time (APTT) ≤ 1.5×ULN Prothrombin Time (PT) ≤ 1.5×ULN International Normalized Ratio (INR) ≤ 1.5×ULN -Female patients must meet the following criteria:
• Be in a postmenopausal state (defined as having had no menstruation for at least 1 year, with no other confirmed cause for amenorrhea other than menopause), or have undergone surgical sterilization (removal of ovaries and/or uterus); alternatively, patients with reproductive potential must simultaneously meet the following requirements:
• A serum pregnancy test result must be negative within 7 days prior to randomization;
• Agree to use a contraceptive method with an annual failure rate of \< 1% or practice abstinence (avoidance of heterosexual intercourse) (from the time of signing the informed consent form until at least 120 days after the last dose of the investigational drug, and at least 6 \[months\] after the last dose of the chemotherapy drug ...months (contraceptive methods with an annual failure rate of \< 1% include bilateral tubal ligation, vasectomy, correct use of ovulation-suppressing hormonal contraceptives, hormone-releasing intrauterine devices \[IUDs\], and copper-containing IUDs);
• Must not be breastfeeding. -Male patients must meet the following criteria: Agree to practice abstinence (avoid heterosexual intercourse) or use contraception, as specified below: If the partner is a female of childbearing potential or is pregnant, the male patient must practice abstinence or correctly use condoms for contraception-to prevent drug exposure to the embryo-during the chemotherapy treatment period and for at least 6 months after the last dose of chemotherapy medication, and for at least 120 days after the last dose of the investigational drug. The reliability of sexual abstinence should be evaluated with reference to the duration of the clinical study, patient preference, and lifestyle. Periodic abstinence (e.g., calendar-based, ovulation-based, basal body temperature, or post-ovulation methods) and withdrawal (coitus interruptus) are not considered acceptable methods of contraception.

You may not qualify if:

• History of other active malignancies within the past 5 years, or the presence of other active malignancies at the time of enrollment. Patients with cured localized tumors-such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, or carcinoma in situ of the breast-are eligible for enrollment.
• Presence of documented distant metastases (e.g., liver, lung, or bone metastases) or laparoscopically confirmed peritoneal seeding (P1).
• Patients scheduled to undergo, or with a history of having undergone, organ or bone marrow transplantation.
• Occurrence of myocardial infarction or poorly controlled arrhythmias (including a QTc interval ≥ 450 ms for males or ≥ 470 ms for females; QTc interval calculated using the Fridericia formula) within 6 months prior to enrollment.
• Presence of NYHA Class III or IV heart failure, or a cardiac ultrasound result showing a Left Ventricular Ejection Fraction (LVEF) \< 50%.
• Human Immunodeficiency Virus (HIV) infection.
• Presence of active pulmonary tuberculosis.
• History of, or current presence of, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-induced pneumonitis, or severe impairment of pulmonary function that could interfere with the detection or management of suspected drug-related pulmonary toxicity.
• Presence of a known active or suspected autoimmune disease. Exceptions are made for patients whose disease is in a stable state at the time of enrollment (defined as requiring no systemic immunosuppressive therapy).
• Receipt of a live vaccine within 28 days prior to enrollment; inactivated viral vaccines for seasonal influenza are permitted.
• Patients requiring systemic corticosteroid therapy (at a prednisone-equivalent dose \> 10 mg/day) or other immunosuppressive medications within 14 days prior to enrollment or during the study period. However, the following exceptions are permitted: in the absence of active autoimmune disease, patients may use topical or inhaled corticosteroids, or receive adrenal replacement therapy at a prednisone-equivalent dose ≤ 10 mg/day.
• Presence of any active infection requiring systemic anti-infective treatment within 14 days prior to enrollment; prophylactic antibiotic treatment (e.g., for the prevention of urinary tract infections or chronic obstructive pulmonary disease) is an exception.
• Prior receipt of any anti-tumor therapy for the current gastric cancer, including chemotherapy, radiotherapy, targeted therapy, or immunotherapy.
• Currently receiving treatment in another clinical study, or the planned start date of the treatment in this study is less than 14 days after the completion of treatment in a previous clinical study.
• Known history of severe allergy to any monoclonal antibody or excipients of the investigational drug.

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead

MeSH Terms

Interventions

Hyperthermic Intraperitoneal Chemotherapy; S 1 (combination); Capecitabine; Oxaliplatin

Intervention Hierarchy (Ancestors)

Chemotherapy, Adjuvant; Combined Modality Therapy; Therapeutics; Drug Therapy; Hyperthermia, Induced; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Shanghai Changzheng Hospital

Model Details: All enrolled participants will undergo HIPEC followed by serplulimab-based neoadjuvant therapy prior to radical gastrectomy.

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: June 2, 2026
• Study Start: May 10, 2026
• Primary Completion (Estimated): May 9, 2028
• Study Completion (Estimated): May 9, 2028
• Last Updated: June 2, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share