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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Peritoneal Metastases From Colorectal Cancer
• Intervention / Treatment: Biological: CEA-targeted CAR-T cells

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.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lifeng Sun, MD; Phone Number: 0571-87783583; Email: sunlifeng@zju.edu.cn
• Study Contact Backup: Name: Ying Yuan, MD; Phone Number: 0571-87784818; Email: yuanying1999@zju.edu.cn

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310017
      • Recruiting
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
      • Principal Investigator: Lifeng Sun, MD
      • Sub-Investigator: Jian Wang, MD
      • Contact: Lifeng Sun, MD; Phone Number: 0571-87783583; Email: sunlifeng@zju.edu.cn
      • Contact: Ying Yuan, MD; Phone Number: 0571-87784818; Email: yuanying1999@zju.edu.cn
      • Principal Investigator: Ying Yuan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged ≥18 years and ≤75 years at the time of informed consent signing.
2. Pathologically confirmed colorectal cancer with peritoneal metastases.
3. Patients who have failed standard treatments (disease progression or intolerance, e.g., failure of oxaliplatin, irinotecan, fluorouracil, etc.) or have no effective treatment options.
4. 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).
5. Tumor samples resected during cytoreductive surgery are confirmed CEA-positive by immunohistochemistry (distinct membranous staining, positive rate ≥10%).
6. Regardless of synchronous or metachronous peritoneal metastases, there are no metastatic sites outside the peritoneum, and the primary tumor has been resected.
7. Expected survival time of at least 3 months.
8. ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1.

9. Unless otherwise specified, subjects must have adequate organ function as follows:

   1. 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.
   2. Cardiac function: Echocardiography shows left ventricular ejection fraction (LVEF) >50%, and electrocardiogram (ECG) shows no significant abnormalities.
   3. Renal function: Serum creatinine ≤2.0×ULN, blood urea nitrogen (BUN) ≤1.5×ULN.
   4. Liver function: ALT and AST ≤3.0×ULN; total bilirubin ≤2.0×ULN (≤3.0×ULN for Gilbert's syndrome).
   5. Oxygen saturation >92% without oxygen supplementation.
10. 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.
11. Male patients agree to use appropriate contraceptive methods.
12. Able to comply with the study protocol and follow-up procedures.

Exclusion Criteria:

1. Unwilling to sign the informed consent form.
2. Received or are currently receiving anti-tumor drug therapy within 2 weeks prior to enrollment, except for perioperative hyperthermic intraperitoneal chemotherapy.
3. Clinically confirmed active or uncontrolled bacterial, fungal, or viral infections.
4. 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.
5. 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.
6. Have a history of mental illness.
7. 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.
8. 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.
9. Known hypersensitivity to any component of the study product, or other potential hypersensitivity to immunotherapy as deemed by the investigator.
10. Pregnant or lactating women.
11. The investigator judges that the patient has other serious diseases that may affect follow-up and short-term survival.
12. Other situations deemed ineligible by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intraperitoneal infusion of CEA-targeted CAR-T; Infusion of CEA-targeted CAR-T cells by dose of 1-5x10^5 cells/kg	Biological: CEA-targeted CAR-T cells; Administration method: intraperitoneal infusion. Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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]	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	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	From infusion through Month 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	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)	2 years
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.	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.	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.	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.	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.	2 years

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Collaborators: Chongqing Precision Biotech Co., Ltd
• Investigators: Principal Investigator: Ying Yuan, Second Affiliated Hospital, School of Medicine, Zhejiang University; Principal Investigator: Lifeng Sun, Second Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): November 3, 2025
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: November 17, 2025
• First Submitted That Met QC Criteria: November 23, 2025
• First Posted (Actual): November 25, 2025

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 23, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: PBC101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No