Evaluation of Pressurized Intraperitoneal Aerosol Chemotherapy With VRT106 Versus PIPAC in Patients With Advanced Gastric Cancer and PeritonealMetastasis: A Prospective, Multicenter, Open-Label, Randomized Controlled Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This study is a prospective, multicenter, open-label, randomized controlled clinical trial, planned to enroll 30 patients with advanced gastric cancer and peritoneal metastasis. It aims to evaluate the safety and efficacy of systemic therapy plus Pressurized Intra-Peritoneal Aerosol Virus (PIPAV) with VRT106 compared to systemic therapy plus Pressurized Intra-Peritoneal Aerosol Chemotherapy (PIPAC).
详细描述
To evaluate the efficacy and quality of life in different treatment cohorts for patients with advanced gastric cancer and peritoneal metastasis.
To evaluate the biodistribution and biological effects of PIPAV（Pressurized Intra-Peritoneal Aerosol Virus） treatment in patients with advanced gastric cancer and peritoneal metastasis, including viral distribution and shedding characteristics, as well as immunogenicity.
To explore the relationship between pharmacodynamics, biomarkers, and therapeutic efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18 to 75 years, inclusive, regardless of gender.
- •Histologically or pathologically confirmed gastric adenocarcinoma with peritoneal metastasis (confirmed by imaging findings, previous surgical pathology, or positive cytology from ascites/peritoneal fluid), and assessed by the investigator as having unresectable peritoneal lesions with a PCI score >
- •Subjects with no contraindications for laparoscopic surgery.
- •ECOG performance status ≤
- •Expected survival time ≥ 6 months.
- •No blood transfusion or treatment with hematopoietic stimulating factors within 14 days before screening, and meeting the following criteria:
- •Hematology: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelet count (PLT) ≥ 100 × 10⁹/L, hemoglobin (Hb) ≥ 90 g/L.
- •Blood biochemistry: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN) (≤ 3.0 × ULN for subjects with Gilbert syndrome); alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤ 3.0 × ULN; albumin ≥ 2.8 g/dL; creatinine ≤ 1.5 × ULN; or creatinine clearance (Ccr) ≥ 50 mL/min (calculated using the Cockcroft-Gault formula, only required if creatinine > 1.5 × ULN).
- •Coagulation function: Activated partial thromboplastin time (APTT), international normalized ratio (INR), or prothrombin time (PT) ≤ 1.5 × ULN.
- •Female subjects of childbearing potential or male subjects with partners of childbearing potential must use effective contraception throughout the treatment period and for 3 months after the last dose.
- •Voluntary participation in the clinical study, with full understanding and signed informed consent form (ICF); willingness and ability to comply with all trial procedures.
排除标准
- •1. Subjects with gastrointestinal obstruction;
- •Subjects completely dependent on parenteral nutrition;
- •Subjects with decompensated ascites;
- •Subjects with severe abdominal infection (manifesting as peritonitis);
- •Subjects with extensive abdominal adhesions;
- •Subjects undergoing simultaneous cytoreductive surgery and gastrointestinal resection and reconstruction;
- •Subjects with concurrent portal vein thrombosis;
- •Known allergy to any component of the VRT106 formulation (mannitol, human albumin, trehalose, etc.) or to chemotherapy drugs;
- •Use of live attenuated vaccines within 4 weeks prior to the first dose of the study drug, including but not limited to: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccines. Seasonal influenza vaccines for injection are inactivated virus vaccines and are allowed; intranasal influenza vaccines are live attenuated and are not allowed;
- •Use of systemic glucocorticoids (prednisone > 10 mg/day or equivalent dose of similar drugs) or other immunosuppressive therapy within 1 week prior to the first dose of the study drug, except for the following:
- •Use of topical, ocular, intra-articular, intranasal, and inhaled corticosteroids;
- •Use of corticosteroids for prophylactic treatment (e.g., prevention of contrast agent allergy);
- •Use of immunomodulatory drugs, including but not limited to thymosin, interleukin-2, interferon, etc., within 14 days prior to the first dose of the study drug;
- •Subjects with active autoimmune disease or a history of autoimmune disease that may recur. However, subjects with the following diseases are not excluded and may be further screened: a. Type 1 diabetes; b. Hypothyroidism (if controlled by hormone replacement therapy alone); c. Controlled celiac disease; d. Skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia); e. Any other disease not expected to recur in the absence of an external trigger;
- •History of splenectomy;
- •Adverse reactions from prior anti-tumor therapy have not recovered to ≤ Grade 1 per NCI-CTCAE v5.0 (excluding alopecia, chemotherapy-induced Grade 2 neurotoxicity, and other toxicities deemed by the investigator to pose no safety risk);
- •History of severe cardiovascular disease, including but not limited to:
- •Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, second- or third-degree atrioventricular block, QT interval corrected using Fridericia's formula (QTcF) ≥ 480 ms, etc.;
- •Occurrence of acute coronary syndrome, acute myocardial infarction, congestive heart failure, stroke, or other Grade 3 or higher cardiovascular events within 6 months prior to the first dose of the study drug;
- •New York Heart Association (NYHA) functional class ≥ II, or left ventricular ejection fraction (LVEF) < 50%;
- •Poorly controlled hypertension per investigator judgment (hypertension not controlled despite standard treatment: systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg);
- •Uncontrolled active infection requiring systemic therapy;
- •Presence of other invasive malignancies besides the study disease. Exceptions include: cured basal cell or squamous cell carcinoma of the skin, carcinoma in situ (e.g., breast cancer, cervical carcinoma in situ), superficial bladder cancer, or malignancies with no recurrence and no treatment for the past 2 years;
- •Pregnant or breastfeeding women;
- •Subjects deemed by the investigator to have other serious systemic diseases or other reasons making them unsuitable for participation in this clinical trial;
- •Subjects who have received other unmarketed investigational drugs/device therapies within 4 weeks prior to the first dose of the study drug;
- •Concurrent enrollment in another clinical study, except for observational (non-interventional) clinical studies or the follow-up phase of an interventional study (must be judged by the investigator as not impacting the efficacy and safety evaluation of this study).
结局指标
主要结局
Incidence of adverse events
时间窗: From the screening period to 28 days after the last intraperitoneal perfusion treatment during the follow-up period
Incidence of adverse events
Incidence of serious adverse events
时间窗: From the screening period to 28 days after the last intraperitoneal perfusion treatment during the follow-up period
Incidence of serious adverse events
Eastern Cooperative Oncology Group Performance status
时间窗: From the screening period to 28 days after the last intraperitoneal perfusion treatment during the follow-up period
0 - Fully active, able to carry on all pre-disease performance without restriction. 1. \- Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2. \- Ambulatory and capable of all self-care but unable to carry out any work activities; up and about more than 50% of waking hours. 3. \- Capable of only limited self-care; confined to bed or chair more than 50% of waking hours. 4. \- Completely disabled; cannot carry on any self-care; totally confined to bed or chair. 5. \- Dead.
Surgical complications
时间窗: From the screening period to 28 days after the last intraperitoneal perfusion treatment during the follow-up period
Surgical complications
Postoperative pain score (Visual Analogue Scale/VAS score)
时间窗: At the beginning of Cycle 1 (each cycle lasting 28 days), at the beginning of Cycle 2 (each cycle lasting 28 days), and at the beginning of Cycle 3 (each cycle lasting 28 days)
Scores of 1-3 are defined as "mild pain (sleep unaffected)"; 4-6 as "moderate pain (sleep affected)"; 7-10 as "severe pain (sleep severely affected)
次要结局
- Peritoneal cancer index，PCI(At the beginning of Cycle 1 (each cycle lasting 28 days), at the beginning of Cycle 2 (each cycle lasting 28 days), and at the beginning of Cycle 3 (each cycle lasting 28 days))
- Peritoneal regression grading score，PRGS(At the beginning of Cycle 1 (each cycle lasting 28 days), at the beginning of Cycle 2 (each cycle lasting 28 days), and at the beginning of Cycle 3 (each cycle lasting 28 days).)
- Quality of life score(At the beginning of Cycle 1 (each cycle lasting 28 days), at the beginning of Cycle 2 (each cycle lasting 28 days), and at the beginning of Cycle 3 (each cycle lasting 28 days).)