Status:
RECRUITING
Exploratory Clinical Study of Claudin18.2-Targeted CAR-DC and CAR-T Therapy in Advanced Colorectal Cancer
Lead Sponsor:
Second Affiliated Hospital, School of Medicine, Zhejiang University
Conditions:
Colorectal Neoplasia
Eligibility:
All Genders
18-70 years
Phase:
PHASE1
Brief Summary
This is an open-label, single-arm clinical study designed to evaluate the safety and preliminary efficacy of Claudin18.2-targeted CAR-DC combined with CAR-T cell therapy in patients with advanced colo...
Detailed Description
Main purpose: To evaluate the safety of Claudin18.2-targeted CAR-T cells in combination with CAR-DCs in patients with advanced colorectal cancer during the dose-escalation phase. To determine the ma...
Eligibility Criteria
Inclusion
- Participants must have a histologically or cytologically confirmed diagnosis of colonic or rectal adenocarcinoma, with at least one measurable lesion meeting RECIST v1.1 criteria (i.e., a target lesion with a longest diameter ≥10 mm on spiral CT scan, or a lymph node with a short axis ≥15 mm).
- Claudin18.2 expression must be confirmed as positive in tumor tissue by immunohistochemistry (IHC).
- Disease progression following standard treatments, including prior administration of fluoropyrimidines, irinotecan, and oxaliplatin. Disease progression may occur during or after treatment. Prior molecular targeted therapies are allowed.
- ECOG performance status of 0 to 1.
- Expected survival of at least 6 months.
- Toxicities related to prior antitumor treatments must have resolved to baseline or ≤ Grade 1 (except for residual alopecia); peripheral neurotoxicity ≤ Grade 2 is acceptable. The minimum washout period is 4 weeks for chemotherapy and immunotherapy, and 2 weeks for targeted therapy.
- Adequate organ function, defined as follows:
- Hematologic function: Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L, platelet count ≥ 75 × 10\^9/L, and hemoglobin ≥ 9 g/dL. No blood transfusions, granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), or erythropoietin (EPO) allowed within 14 days prior to hematology testing.
- Hepatic function: Total bilirubin (TBIL) \< 1.5 × upper limit of normal (ULN); AST and ALT \< 2.5 × ULN. For patients with Gilbert's syndrome, TBIL \< 2 × ULN. For patients with liver metastases, AST and ALT must be \< 5 × ULN.
- Renal function: Serum creatinine ≤ 1.5 × ULN; or if \> 1.5 × ULN, creatinine clearance (CrCl) ≥ 60 mL/min as calculated by the Cockcroft-Gault formula.
- Coagulation function: Prothrombin time (PT) and activated partial thromboplastin time (APTT) \< 1.5 × ULN; international normalized ratio (INR) \< 1.5 or within the therapeutic range if on anticoagulation therapy.
- Participants of childbearing potential must agree to use effective contraception during the study period.
- Participants must have adequate comprehension and voluntarily sign the informed consent form.
- Willingness to comply with all study-related procedures, including scheduled visits, drug administration, laboratory assessments, and other protocol requirements.
Exclusion
- Tumor-related emergencies requiring immediate intervention, such as malignant pericardial effusion or cardiac tamponade, superior vena cava syndrome, or spinal cord compression.
- Clinically significant cardiovascular disease, including:
- Documented cardiovascular events within the past 6 months, such as myocardial infarction, angina, heart failure, severe arrhythmias, or history of angioplasty, stent implantation, or coronary artery bypass grafting (CABG);
- Prolonged QT/QTcF interval with clinical significance (QT/QTcF \> 470 ms in females or \> 450 ms in males).
- Clinically significant bleeding disorders or coagulopathies, such as hemophilia.
- Active infections including HIV, syphilis, or active hepatitis B or C:
- Hepatitis B: HBV-DNA ≥ 1000 IU/mL;
- Hepatitis C: Positive HCV RNA with abnormal liver function.
- History of involuntary psychiatric hospitalization due to mental illness or other psychiatric disorders deemed unsuitable for treatment by the investigator.
- Presence of autoimmune diseases or chronic use of immunosuppressive agents or corticosteroids.
- Poor medication compliance or inability to adhere to the treatment protocol.
- Any other condition that, in the opinion of the investigator, warrants exclusion from the study.
Key Trial Info
Start Date :
April 8 2025
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
April 1 2027
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT06946615
Start Date
April 8 2025
End Date
April 1 2027
Last Update
April 27 2025
Active Locations (1)
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1
Second Affiliated Hospital, School of Medicine, Zhejiang University
Hangzhou, Zhejiang, China, 310009