CEA CAR-T Therapy After Cytoreduction in Colorectal Cancer Patients With Peritoneal Metastases

Official title

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

Overview

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.

Detailed description

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.

Interventions

• Biological CEA-targeted CAR-T cells
  Administration method: intraperitoneal infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.

Primary outcome measures

• 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] [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] [Time frame: From infusion through Month 3]

Secondary outcome measures (8)

• Peritoneal Progression-Free Survival(PPFS) of CEA CAR-T treatment in advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Effectiveness] [Time frame: 2 years]
• Progression-Free Survival(PFS) of CEA CAR-T treatment in advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Effectiveness] [Time frame: 2 years]
• Overall survival(OS)of CEA CAR-T treatment in advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Effectiveness] [Time frame: 2 years]
• Disease Recurrence/Metastasis Rate of CEA CAR-T treatment in advanced colorectal cancer with peritoneal metastases following cytoreductive surgery [Effectiveness] [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] [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] [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] [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] [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• 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-2. 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 1.
• 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.

Exclusion criteria

• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• The Second Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou

Identifiers

NCT: NCT07247396 · PBC101

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗