Clinical Trials /

A Clinical Research of CAR T Cells Targeting CEA Positive Colorectal Cancer (CRC)

NCT04513431

Description:

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.

Related Conditions:
  • Colorectal Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Early Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: RJBY_anti-CEA CAR-T_CRC01
  • NCT ID: NCT04513431

Conditions

  • Stage III Colorectal Cancer
  • Colorectal Cancer Liver Metastasis

Interventions

DrugSynonymsArms
Anti-CEA-CAR TColorectal cancer

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Colorectal cancerExperimentalColorectal cancer treated with T cells modified with Anti-CEA-CAR T.
  • Anti-CEA-CAR T

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;
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse events that related to treatment
Time Frame:4 weeks
Safety Issue:
Description:Therapy-related adverse events will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)

Secondary Outcome Measures

Measure:Survival time of Anti-CEA CAR T cells in vivo.
Time Frame:3 months
Safety Issue:
Description:To evaluate the presence of circulating CAR T cells with flow cytometry and real time PCR in patient blood.
Measure:Efficacy of anti-CEA CAR T cells to confirm the ability of CAR T cells to kill CEA positive cancer cells
Time Frame:6 months
Safety Issue:
Description:To evaluate the presence of circulating tumor cells with flow cytometry and real time PCR in patient blood.
Measure:Maximum tolerated dose (MTD) of CEA targeted CAR T cells
Time Frame:4 weeks
Safety Issue:
Description:To confirm the maximum tolerated dose of CEA targeted CAR T cells.

Details

Phase:Early Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Ruijin Hospital

Last Updated

August 11, 2020