Clinical trial NCT04513431: A Clinical Research of CAR T Cells Targeting CEA Positive Colorectal Cancer (CRC)
Official title: A Study Evaluating the Safety and Preliminary Efficacy of Anti-CEA CAR-T Cells for the Prevention of Postoperative Recurrence and Metastasis of Stage III Colorectal Cancer or Liver Metastasis of Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Stage III Colorectal Cancer
Colorectal Cancer Liver Metastasis
Lead sponsor: Ruijin Hospital
Sponsor class: OTHER
Collaborators: name: HuaDao (Shanghai) Biomedical Co., Ltd.
First posted: 2020-08-14
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: The main purpose of this research is to verify the safety of CEA targeted chimeric antigen receptor T cells and to determine the proper dosage of CAR T cells infused.

Detailed description: Chimeric antigen receptor (CAR)-modified T cells have demonstrated great successes in treating even late stage cluster of differentiation antigen 19 (CD19) positive B cell malignancies. But it has few studies in solid tumors. The carcino-embryonic antigen(CEA) is widely expressed in cancers like gastric cancer, lung cancer, pancreatic cancer, breast cancer and colorectal cancer. To confirm if CAR T cells still function in solid tumors, we have developed anti-CEA CAR-modified T cells. Preclinical studies have demonstrated effective killing of CEA target cells. In this study, the CEA CARs, will be evaluated in CEA positive gastric cancer. The primary goal is to confirm its adverse effects including cytokine storm response and any other adverse effects. In addition, tumor targeting and disease status after treatment will also be evaluated.

Eligibility criteria: Inclusion Criteria:

1. CEA positive T4/N2 high-risk stage-Ⅲ colorectal cancer after surgery or patients with colorectal cancer liver metastasis after R0 surgery;
2. Patients whose serum CEA ≥11 ng/mL;
3. Life expectancy ≥ 3 months;
4. PS score 0-2, KPS score ≥60;
5. \>3 CTC/7.5 mL blood sample;
6. Patients who plan to use XELOX chemotherapy after surgery;
7. Patients must have adequate organ function , such as NYHA heart function classification grade III or higher, no severe anemia, hypoxia; liver function: total bilirubin ≤ 1.5 × ULN (total bilirubin ≤ 3 × ULN when liver metastasis), ALT≤2.5×ULN, AST≤2.5×ULN (ALT or/and AST≤5×ULN when liver metastasis); renal function: blood creatinine ≤1.5 × ULN and creatinine clearance ≥50 mL/min, only when blood creatinine ≤ Calculate the creatinine clearance rate when 1.5 × ULN;
8. Sufficient peripheral blood can be obtained through peripheral veins without contraindications to apheresis;
9. Patients of childbearing age have no birth plans and take effective contraceptive measures during the study period and within 1 year after the study.

Exclusion Criteria:

1. Patients who have a history of severe central nervous system disease;
2. Other organ metastases except liver;
3. Patients who have non malignant diseases, including autoimmune diseases, primary immunodeficiency diseases or obstructive or restrictive respiratory diseases;
4. Patients received car-t or other gene modified T cell therapy previously;
5. Patients who plan to use other targeted anti-tumor drugs;
6. Patients who participated in other clinical studies within 30 days before screening or planned to participate in other clinical studies during the study period;
7. Patients who have syphilis or HIV / HBV / HCV / HPV / EBV / CMV infection ; HBV-DNA copy number ≥ 1 × 10 \^ 5 copies / ml is required for HBV seropositive patients;
8. Patients who have uncontrollable systemic infectious diseases;
9. Patients who have multiple malignant tumor;
10. Patients who received or may need Chinese herbal medicine, systemic glucocorticoid or other immunosuppressants within 2 weeks before enrollment;
11. Patient who are pregnancy and lactating;
12. Patients who have severe gastroduodenal ulcer, ulcerative colitis and other intestinal inflammation;

Primary outcomes:
measure: Adverse events that related to treatment
timeFrame: 4 weeks
Secondary outcomes:
measure: Survival time of Anti-CEA CAR T cells in vivo.
timeFrame: 3 months
measure: Efficacy of anti-CEA CAR T cells to confirm the ability of CAR T cells to kill CEA positive cancer cells
timeFrame: 6 months
measure: Maximum tolerated dose (MTD) of CEA targeted CAR T cells
timeFrame: 4 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Ruijin Hospital
name: Ren Zhao, Medical PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ruijin Hospital
name: Mei Wang, Medical PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Ruijin Hospital
name: Chen xianze, Medical PhD
role: STUDY_CHAIR
affiliation: Ruijin Hospital
name: Liu Kun, Medical PhD
role: STUDY_CHAIR
affiliation: Ruijin Hospital
name: Shi Yiqing, Medical PhD
role: STUDY_CHAIR
affiliation: Ruijin Hospital
name: Wang Chen, Medical PhD
role: STUDY_CHAIR
affiliation: Ruijin Hospital
name: He Qianyun, Medical PhD
role: STUDY_CHAIR
affiliation: Ruijin Hospital
name: Mao Dongliang, Medical PhD
role: STUDY_CHAIR
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