Back to resultsA Clinical Research of CAR T Cells Targeting CEA Positive Colorectal Cancer (CRC) (CRC)
Primary Purpose
Stage III Colorectal Cancer, Colorectal Cancer Liver Metastasis
Status
Unknown status
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Anti-CEA-CAR T
Sponsored by
About this trial
This is an interventional prevention trial for Stage III Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- CEA positive T4/N2 high-risk stage-Ⅲ colorectal cancer after surgery or patients with colorectal cancer liver metastasis after R0 surgery;
- Patients whose serum CEA ≥11 ng/mL;
- Life expectancy ≥ 3 months;
- PS score 0-2, KPS score ≥60;
- >3 CTC/7.5 mL blood sample;
- Patients who plan to use XELOX chemotherapy after surgery;
- 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;
- Sufficient peripheral blood can be obtained through peripheral veins without contraindications to apheresis;
- 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:
- Patients who have a history of severe central nervous system disease;
- Other organ metastases except liver;
- Patients who have non malignant diseases, including autoimmune diseases, primary immunodeficiency diseases or obstructive or restrictive respiratory diseases;
- Patients received car-t or other gene modified T cell therapy previously;
- Patients who plan to use other targeted anti-tumor drugs;
- Patients who participated in other clinical studies within 30 days before screening or planned to participate in other clinical studies during the study period;
- 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;
- Patients who have uncontrollable systemic infectious diseases;
- Patients who have multiple malignant tumor;
- Patients who received or may need Chinese herbal medicine, systemic glucocorticoid or other immunosuppressants within 2 weeks before enrollment;
- Patient who are pregnancy and lactating;
- Patients who have severe gastroduodenal ulcer, ulcerative colitis and other intestinal inflammation;
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Colorectal cancer
Arm Description
Colorectal cancer treated with T cells modified with Anti-CEA-CAR T.
Outcomes
Primary Outcome Measures
Adverse events that related to treatment
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
Survival time of Anti-CEA CAR T cells in vivo.
To evaluate the presence of circulating CAR T cells with flow cytometry and real time PCR in patient blood.
Efficacy of anti-CEA CAR T cells to confirm the ability of CAR T cells to kill CEA positive cancer cells
To evaluate the presence of circulating tumor cells with flow cytometry and real time PCR in patient blood.
Maximum tolerated dose (MTD) of CEA targeted CAR T cells
To confirm the maximum tolerated dose of CEA targeted CAR T cells.
Full Information
NCT ID
NCT04513431
First Posted
July 31, 2020
Last Updated
August 11, 2020
Sponsor
Ruijin Hospital
Collaborators
HuaDao (Shanghai) Biomedical Co., Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04513431
Brief Title
A Clinical Research of CAR T Cells Targeting CEA Positive Colorectal Cancer (CRC)
Acronym
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
2. Study Status
Record Verification Date
August 2020
Overall Recruitment Status
Unknown status
Study Start Date
August 30, 2020 (Anticipated)
Primary Completion Date
March 30, 2021 (Anticipated)
Study Completion Date
August 30, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ruijin Hospital
Collaborators
HuaDao (Shanghai) Biomedical Co., Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stage III Colorectal Cancer, Colorectal Cancer Liver Metastasis
7. Study Design
Primary Purpose
Prevention
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Colorectal cancer
Arm Type
Experimental
Arm Description
Colorectal cancer treated with T cells modified with Anti-CEA-CAR T.
Intervention Type
Biological
Intervention Name(s)
Anti-CEA-CAR T
Intervention Description
T cells modified with CEA targeted chimeric antigen receptor.
Primary Outcome Measure Information:
Title
Adverse events that related to treatment
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)
Time Frame
4 weeks
Secondary Outcome Measure Information:
Title
Survival time of Anti-CEA CAR T cells in vivo.
Description
To evaluate the presence of circulating CAR T cells with flow cytometry and real time PCR in patient blood.
Time Frame
3 months
Title
Efficacy of anti-CEA CAR T cells to confirm the ability of CAR T cells to kill CEA positive cancer cells
Description
To evaluate the presence of circulating tumor cells with flow cytometry and real time PCR in patient blood.
Time Frame
6 months
Title
Maximum tolerated dose (MTD) of CEA targeted CAR T cells
Description
To confirm the maximum tolerated dose of CEA targeted CAR T cells.
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
CEA positive T4/N2 high-risk stage-Ⅲ colorectal cancer after surgery or patients with colorectal cancer liver metastasis after R0 surgery;
Patients whose serum CEA ≥11 ng/mL;
Life expectancy ≥ 3 months;
PS score 0-2, KPS score ≥60;
>3 CTC/7.5 mL blood sample;
Patients who plan to use XELOX chemotherapy after surgery;
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;
Sufficient peripheral blood can be obtained through peripheral veins without contraindications to apheresis;
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:
Patients who have a history of severe central nervous system disease;
Other organ metastases except liver;
Patients who have non malignant diseases, including autoimmune diseases, primary immunodeficiency diseases or obstructive or restrictive respiratory diseases;
Patients received car-t or other gene modified T cell therapy previously;
Patients who plan to use other targeted anti-tumor drugs;
Patients who participated in other clinical studies within 30 days before screening or planned to participate in other clinical studies during the study period;
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;
Patients who have uncontrollable systemic infectious diseases;
Patients who have multiple malignant tumor;
Patients who received or may need Chinese herbal medicine, systemic glucocorticoid or other immunosuppressants within 2 weeks before enrollment;
Patient who are pregnancy and lactating;
Patients who have severe gastroduodenal ulcer, ulcerative colitis and other intestinal inflammation;
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mei Wang, Medical PhD
Phone
+86-13601810867
Email
13601810867@163.com
First Name & Middle Initial & Last Name or Official Title & Degree
Lin Tian, Medical PhD
Phone
13651760950
Email
lin.tian@huadaocart.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ren Zhao, Medical PhD
Organizational Affiliation
Ruijin Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mei Wang, Medical PhD
Organizational Affiliation
Ruijin Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Chen xianze, Medical PhD
Organizational Affiliation
Ruijin Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Liu Kun, Medical PhD
Organizational Affiliation
Ruijin Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Shi Yiqing, Medical PhD
Organizational Affiliation
Ruijin Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Wang Chen, Medical PhD
Organizational Affiliation
Ruijin Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
He Qianyun, Medical PhD
Organizational Affiliation
Ruijin Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Mao Dongliang, Medical PhD
Organizational Affiliation
Ruijin Hospital
Official's Role
Study Chair
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Clinical Research of CAR T Cells Targeting CEA Positive Colorectal Cancer (CRC)
We'll reach out to this number within 24 hrs