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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Administration method: intraperitoneal infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
The Second Affiliated Hospital of Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
RECRUITINGTo evaluate the safety of CAR-T cell preparations in the treatment of advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Safety and Tolerability]
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
Time frame: From infusion through Month 3
Obtained the recommended dose of CAR-T cells for the treatment of advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Safety and Tolerability]
Dose-limiting toxicity after CEA CAR-T cell infusion
Time frame: From infusion through Month 3
Peritoneal Progression-Free Survival(PPFS) of CEA CAR-T treatment in advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Effectiveness]
PPFS will be assessed from the first CEA-CAR-T cell infusion to death from any cause or the first assessment of progression(Assessed based on RECIST criteria)
Time frame: 2 years
Progression-Free Survival(PFS) of CEA CAR-T treatment in advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Effectiveness]
PFS will be assessed from the first CEA-CAR-T cell infusion to death from any cause or the first assessment of progression(Assessed based on RECIST criteria)
Time frame: 2 years
Overall survival(OS)of CEA CAR-T treatment in advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Effectiveness]
OS will be assessed from the first CEA-CAR-T cell infusion to death from any cause (Assessed by investigators based on IRECIST criteria)
Time frame: 2 years
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Disease Recurrence/Metastasis Rate of CEA CAR-T treatment in advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Effectiveness]
The proportion of patients who experience disease recurrence or metastasis within a specified time period after CAR-T cell infusion.
Time frame: 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]
Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Graded according to ASTCT consensus criteria (Grade 1-5). The incidence of all grades and grade ≥3 toxicities, median onset time and duration, utilization rate of symptomatic treatments (e.g., corticosteroids), and temporal correlation between the occurrence of CRS and ICANS will be analyzed. On-target/off-tumor toxicity involving CEA-expressing organs: The incidence of gastrointestinal toxicity (e.g., oral mucositis, diarrhea, colitis) and pulmonary toxicity (e.g., immune-related pneumonia) will be evaluated.
Time frame: 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]
To determine the time to maximum observed concentration (Tmax) of circulating CAR-T cells.
Time frame: 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]
To estimate the area under the concentration-time curve from time 0 to 28 days (AUC₀-₂₈d) and from time 0 to 90 days (AUC₀-₉₀d) for circulating CAR-T cells.
Time frame: 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]
Immunogenicity: Incidence of anti-CAR antibodies will be assessed. Delayed toxicity: Occurrence of events such as secondary malignancies will be evaluated.
Time frame: 2 years