The Efficacy and Safety of HIPEC Combined With PD-1 and SOX Chemotherapy for the Translational Treatment of GC or EGJC With PM

NCT06427252 | Active Not Recruiting Phase 2

• 1 other identifier: HISTORIA
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Gastric cancer (GC) with peritoneal metastasis has a poor prognosis and short survival. In recent years, heat intraperitoneal perfusion chemotherapy (HIPEC) has gained better efficacy in the treatment of peritoneal metastases of many malignant tumors, including GC with peritoneal metastasis. The use of immune checkpoint inhibitors (ICIs) in the treatment of advanced GC has made significant progress in recent years. And studies showed that patients who were responded to immunotherapy combined with chemotherapy as the first-line treatment were able to achieve significant survival benefit after radical resection. However, whether HIPEC combined with immunotherapy for peritoneal metastatic gastric cancer improves the R0 resection rate and prolongs survival time is currently unclear. Therefore, we conducted this prospective multicenter clinical trial to explore the effective dose and safety of the combination of systemic chemotherapy, HIPEC, anti-PD-1 and anti-HER-2 therapy, which will provide a clinical basis for the treatment of advanced GC.

Conditions

Gastric Cancer, Metastatic

Keywords

gastric cancer; peritoneal metastasis; HIPEC; immunotherapy

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  The proportion of patients still alive at one year from the start of patient enrollment was calculated as a percentage of all patients. Deaths from all causes were included in the calculation of overall survival. The OS of patients who did not reach the one-year loss to follow-up was counted as data censored at the time of last confirmed survival before the loss to follow-up, i.e., only the time point of last known survival was counted in the number of survivors.

  1 year

Secondary Outcomes (3)

• Progression-free Survival

  1 year

• Completeness of cytoreduction score

  1 year

• Objective Response Rate

  1 year

Study Arms (1)

HIPEC plus PD-1 plus SOX therapy

EXPERIMENTAL

HIPEC treatment (paclitaxel, at 43°C for 60 min) was performed on the 1st day after the first exploratory laparotomy and on the third day after the radical surgery for a total of 2-3 times (total amount of paclitaxel was 175 mg/m2 ). Systemic therapy was started 3 weeks after HIPEC. Systemic therapy including: Tirilizumab: 200 mg, Q3W; oxaliplatin: 130mg/m2, Q3W; Herceptin: loading dose of 8 mg/kg followed by 6 mg/kg Q3W. Tegeo: Oral administration: 40 mg per dose for BSA \<1.25, 50 mg per dose for BSA 1.25 to 1.5, and 60 mg per dose for BSA ≥1.5, twice daily for each treatment cycle Q3W; After 2-6 weeks, laparoscopic exploration was performed, PCI score was calculated, and radical surgery was performed in patients who were eligible for radical surgery. Postoperative HIPEC was performed twice.

Drug: HIPEC; Drug: Systemic therapy

Interventions

HIPEC DRUG

In the experimental group, HIPEC treatment (paclitaxel, 3000 ml of physiological saline at 43°C for 60 min) was performed on the first day after the first exploratory laparotomy and on the third day after the radical surgery for a total of 2-3 times (total amount of paclitaxel was 175 mg/m2 ), with an interval of not more than 72 h. Intravenous systemic therapy was started 3 weeks after the completion of HIPEC treatment. systemic therapy.

HIPEC plus PD-1 plus SOX therapy

Systemic therapy DRUG

1. Tirilizumab: 200 mg, i.v., D1, Q3W; 2. oxaliplatin: 130mg/m2, i.v., D1, Q3W; 3. Herceptin: a tri-weekly dosing regimen with an initial loading dose of 8 mg/kg followed by 6 mg/kg Q3W. 4. Tegeo: Oral administration: 40 mg per dose for BSA \<1.25, 50 mg per dose for BSA 1.25 to 1.5, and 60 mg per dose for BSA ≥1.5, twice daily for each treatment cycle D1-D14, Q3W;

HIPEC plus PD-1 plus SOX therapy

Eligibility Criteria

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

You may qualify if:

• patients with a pathologically confirmed primary diagnosis of gastric/esophagogastric junctional cancer who have not undergone chemotherapy, radiotherapy, or other antitumor therapy prior to the start of the clinical trial;
• age 18 to 75 years Eastern Coorperative Oncology Group (ECOG): 0 to 1 points;
• diagnosis of metastatic adenocarcinoma of the peritoneum \[peritoneal cancer index (PCI) ≤ 20 points\] with or without ascites (beyond the pelvis but not reaching full abdominal ascites) by laparoscopic exploration;
• Voluntarily sign the informed consent form.
• good cardiac function for resection with curative intent. If clinically indicated, patients with underlying ischemic, valvular heart disease or other severe heart disease should be evaluated preoperatively by a cardiologist;
• normal function of major organs and subjects are required to meet the following laboratory criteria: 1) Absolute neutrophil count (ANC) ≥ 1.5x109/L in the last 14 days without granulocyte colony-stimulating factor (GCSF); 2) Platelets ≥ 100 x 109/L in the absence of blood transfusion in the last 14 days; 3) Hemoglobin \> 9 g/dL without transfusion or erythropoietin use in the last 14 days; 4) Total bilirubin ≤ 1.5 x upper limit of normal (ULN); enrollment is also allowed if total bilirubin \> 1.5 x ULN but direct bilirubin ≤ ULN; 5) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN.
• \) Blood creatinine ≤1.5×ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) ≥60 ml/min; 7) good coagulation function, defined as International Normalized Ratio (INR) or Prothrombin Time (PT) ≤ 1.5 x ULN; 8) Normal thyroid function, defined as thyrotropin (TSH) within the normal range. If baseline TSH is outside the normal range, subjects may also be enrolled if total T3 (or FT3) and FT4 are within the normal range; 9) Cardiac enzyme profiles within the normal range (enrollment will be allowed if the investigator determines that the laboratory abnormality is not of clinical significance); 7) Thyroid function: thyroid stimulating hormone (TSH) and free thyroxine (FT3/FT4) in the normal range or mildly abnormal without clinical significance; 8. weight of 40 kg or more (including 40 kg), or BMI \> 18.5; 9. female patients must meet:
• Menopausal (defined as absence of menstruation for at least 1 year with no confirmed cause other than menopause) status, or surgically sterilized (removal of ovaries and/or uterus), or patients of childbearing potential must also meet the following requirements:
• Pregnancy test within 7 days prior to first dose must be negative;
• Agree to use contraception with an annual failure rate of \< 1% or remain abstinent (avoid heterosexual intercourse) (at least 120 days from signing the informed consent form until at least 9 months after the last dose of the test drug and at least 9 months after the procedure (contraceptive methods with an annual failure rate of \< 1% include bilateral tubal ligation, male sterilization, proper use of hormonal contraceptives that suppress ovulation, hormone-releasing intrauterine contraceptives, and copper-containing intrauterine devices). .;
• No breastfeeding is allowed. 10. The subject reads and fully understands the patient instructions and signs the informed consent form.

You may not qualify if:

• the patient has a previous (within 5 years) or concurrent other malignant tumor;
• patients who are preparing for or have previously received organ or bone marrow transplantation;
• have had a blood transfusion within 2 weeks prior to the first dose, or have a history of bleeding, and any bleeding event with a severity rating of 3 or more on the CTCAE 4.0 within 4 weeks prior to screening;
• abnormal coagulation with bleeding tendency (INR in the absence of anticoagulants at normal values \> 1.5); patients treated with anticoagulants or vitamin K antagonists such as warfarin, heparin, or their analogues; the use of low-dose warfarin (1 mg orally once daily) for prophylactic purposes is permitted, provided the International Normalized Ratio of the prothrombinogen time (INR) is ≤ 1.5, or Small-dose aspirin (no more than 100 mg daily);
• an actinic/venous thrombotic event within 6 months prior to screening, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis (except for venous thrombosis due to intravenous cannulation for pre-chemotherapy, which has resolved in the judgment of the investigator), and pulmonary embolism;
• myocardial infarction, poorly controlled arrhythmia (including QTc interval ≥ 450 ms in men and ≥ 470 ms in women) within 6 months prior to the first dose (QTc interval is calculated using the Fridericia formula);
• the presence of NYHA class III-IV cardiac insufficiency or cardiac ultrasound: LVEF (left ventricular ejection fraction) \<50%;
• urine protein ≥++ and confirmed 24-hour urine protein quantification \>1.0 g;
• have multiple factors that interfere with oral administration of medications (e.g., inability to swallow, chronic diarrhea, and intestinal obstruction)
• pleural effusion with clinical symptoms requiring clinical intervention;
• human immunodeficiency virus (HIV) infection;
• active tuberculosis;
• long-standing unhealed wounds or incompletely healed fractures;
• patients with pre-existing and current interstitial pneumonitis, pneumoconiosis, radiation pneumonitis, drug-associated pneumonitis, and severely impaired lung function that may interfere with the detection and management of suspected drug-associated pulmonary toxicity
• the presence of a known active or suspected autoimmune disease, except those who are in a stable state of that disease at the time of enrollment (not requiring systemic immunosuppressive therapy);

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

The First Affiliated Hospital of Nanjing Medical University

Nanjing, Jiangsu, 210029, China

Location

Related Publications (1)

• Zhang Y, Li F, Liu H, Li P, Li Q, Wang L, Zhang D, Wu H, Xu H, Yang L, Xu ZK. Efficacy and safety of HIPEC combined with PD-1 and SOX chemotherapy for gastric or oesophagogastric junctional cancer with peritoneal metastasis (HISTORIA): protocol for a prospective, multicentre, single-arm, phase II study. BMJ Open. 2025 Sep 14;15(9):e098326. doi: 10.1136/bmjopen-2024-098326.

  PMID: 40953882 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms; Neoplasm Metastasis

Interventions

Hyperthermic Intraperitoneal Chemotherapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chemotherapy, Adjuvant; Combined Modality Therapy; Therapeutics; Drug Therapy; Hyperthermia, Induced

Study Officials

• Zekuan Xu, PhD

  The First Affiliated Hospital with Nanjing Medical University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2024
• First Posted: May 23, 2024
• Study Start: May 31, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): May 31, 2027
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

CN (1)