NCT07247396招募中1 期
A Clinical Trial to Evaluate the Safety and Efficacy of CEA-Directed CAR-T Cell Immunotherapy in Patients With Advanced Colorectal Cancer and Peritoneal Metastases Following Cytoreductive Surgery
Second Affiliated Hospital, School of Medicine, Zhejiang University1 个研究点 分布在 1 个国家目标入组 12 人开始时间: 2025年11月3日最近更新:
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- To evaluate the safety of CAR-T cell preparations in the treatment of advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Safety and Tolerability]
研究概览
简要总结
This single-arm, open-label, dose-escalation trial aims to evaluate the safety and efficacy of CEA-targeted CAR-T cells and to obtain their pharmacokinetic profile in patients with advanced colorectal cancer and peritoneal metastases after cytoreductive surgery; the recommended dose will then be derived from these data.
详细描述
This is a single-arm, open-label, dose-escalation study to evaluate the safety, preliminary efficacy, and pharmacokinetics of CEA-targeted autologous CAR-T cells administered by intraperitoneal infusion in patients with advanced colorectal cancer and peritoneal metastases following cytoreductive surgery. Three dose levels will be tested: 1 × 10⁵, 3 × 10⁵, and 5 × 10⁵ CAR⁺ cells/kg.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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 years and ≤75 years at the time of informed consent signing.
- •Pathologically confirmed colorectal cancer with peritoneal metastases.
- •Patients who have failed standard treatments (disease progression or intolerance, e.g., failure of oxaliplatin, irinotecan, fluorouracil, etc.) or have no effective treatment options.
- •Underwent cytoreductive surgery for peritoneal metastases from colorectal cancer, with cytoreduction completeness (CC) score of CC-0 to CC-
- •Postoperative recovery is good, without severe postoperative complications. A baseline enhanced whole-abdominal CT scan (within 1 week before or after 1 month post-surgery) shows no distant metastases outside the peritoneum (e.g., liver, lung, bone, brain).
- •Tumor samples resected during cytoreductive surgery are confirmed CEA-positive by immunohistochemistry (distinct membranous staining, positive rate ≥10%).
- •Regardless of synchronous or metachronous peritoneal metastases, there are no metastatic sites outside the peritoneum, and the primary tumor has been resected.
- •Expected survival time of at least 3 months.
- •ECOG (Eastern Cooperative Oncology Group) performance status of 0 or
- •Unless otherwise specified, subjects must have adequate organ function as follows:
- •Hematology: White blood cell (WBC) count ≥3.5×10⁹/L, neutrophil count ≥1.8×10⁹/L, lymphocyte count >0.5×10⁹/L, platelet count ≥80×10⁹/L, hemoglobin ≥90g/L.
- •Cardiac function: Echocardiography shows left ventricular ejection fraction (LVEF) >50%, and electrocardiogram (ECG) shows no significant abnormalities.
- •Renal function: Serum creatinine ≤2.0×ULN, blood urea nitrogen (BUN) ≤1.5×ULN.
- •Liver function: ALT and AST ≤3.0×ULN; total bilirubin ≤2.0×ULN (≤3.0×ULN for Gilbert's syndrome).
- •Oxygen saturation >92% without oxygen supplementation.
- •Women of childbearing potential have a negative pregnancy test within 7 days prior to enrollment, have no immediate plans for pregnancy, and agree to use contraceptive measures (or other fertility control methods) before and during the trial.
- •Male patients agree to use appropriate contraceptive methods.
- •Able to comply with the study protocol and follow-up procedures.
排除标准
- •Unwilling to sign the informed consent form.
- •Received or are currently receiving anti-tumor drug therapy within 2 weeks prior to enrollment, except for perioperative hyperthermic intraperitoneal chemotherapy.
- •Clinically confirmed active or uncontrolled bacterial, fungal, or viral infections.
- •Have other uncured malignant tumors, except for carcinoma in situ of the lung, carcinoma in situ of the cervix, or basal cell carcinoma of the skin.
- •Have a history of severe asthma, active autoimmune disease, immunodeficiency, or require long-term immunosuppressive drug therapy; exceptions include vitiligo, type 1 diabetes, autoimmune-related hypothyroidism requiring hormonal therapy, and psoriasis not requiring systemic treatment.
- •Have a history of mental illness.
- •Have uncontrolled comorbidities, including but not limited to symptomatic congestive heart failure, unstable angina, arrhythmia; severe coronary artery disease or cerebrovascular disease, or other diseases deemed ineligible by the investigator.
- •Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) with HBV DNA titer above the normal range; positive for hepatitis C virus (HCV) antibody with HCV RNA above the normal range; positive for human immunodeficiency virus (HIV) antibody; positive for syphilis.
- •Known hypersensitivity to any component of the study product, or other potential hypersensitivity to immunotherapy as deemed by the investigator.
- •Pregnant or lactating women.
- •The investigator judges that the patient has other serious diseases that may affect follow-up and short-term survival.
- •Other situations deemed ineligible by the investigator.
研究组 & 干预措施
Intraperitoneal infusion of CEA-targeted CAR-T
Experimental
Infusion of CEA-targeted CAR-T cells by dose of 1-5x10^5 cells/kg
干预措施: CEA-targeted CAR-T cells (Biological)
结局指标
主要结局
To evaluate the safety of CAR-T cell preparations in the treatment of advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Safety and Tolerability]
时间窗: From infusion through Month 3
Incidence of adverse events during the study, evaluated per the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) criteria
Obtained the recommended dose of CAR-T cells for the treatment of advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Safety and Tolerability]
时间窗: From infusion through Month 3
Dose-limiting toxicity after CEA CAR-T cell infusion
次要结局
- Peritoneal Progression-Free Survival(PPFS) of CEA CAR-T treatment in advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Effectiveness](2 years)
- Progression-Free Survival(PFS) of CEA CAR-T treatment in advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Effectiveness](2 years)
- Overall survival(OS)of CEA CAR-T treatment in advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Effectiveness](2 years)
- Disease Recurrence/Metastasis Rate of CEA CAR-T treatment in advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Effectiveness](2 years)
- To evaluate the toxicity related to CAR-T cell preparations in the treatment of advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Safety](From infusion through Month 3)
- To evaluate the long-term biosafety of CAR-T cell preparations in the treatment of advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Pharmacokinetics](From infusion through Month 3)
- To evaluate the long-term biosafety of CAR-T cell preparations in the treatment of advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Safety](2 years)
研究者
研究点 (1)
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