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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Stage III Colorectal Cancer; Colorectal Cancer Liver Metastasis
• Intervention / Treatment: Biological: Anti-CEA-CAR T

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.

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Mei Wang, Medical PhD; Phone Number: +86-13601810867; Email: 13601810867@163.com
• Study Contact Backup: Name: Lin Tian, Medical PhD; Phone Number: 13651760950; Email: lin.tian@huadaocart.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: Colorectal cancer; Colorectal cancer treated with T cells modified with Anti-CEA-CAR T.	Biological: Anti-CEA-CAR T; T cells modified with CEA targeted chimeric antigen receptor.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	3 months
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.	6 months
Maximum tolerated dose (MTD) of CEA targeted CAR T cells	To confirm the maximum tolerated dose of CEA targeted CAR T cells.	4 weeks

Collaborators and Investigators

• Sponsor: Ruijin Hospital
• Collaborators: HuaDao (Shanghai) Biomedical Co., Ltd.
• Investigators: Principal Investigator: Ren Zhao, Medical PhD, Ruijin Hospital; Principal Investigator: Mei Wang, Medical PhD, Ruijin Hospital; Study Chair: Chen xianze, Medical PhD, Ruijin Hospital; Study Chair: Liu Kun, Medical PhD, Ruijin Hospital; Study Chair: Shi Yiqing, Medical PhD, Ruijin Hospital; Study Chair: Wang Chen, Medical PhD, Ruijin Hospital; Study Chair: He Qianyun, Medical PhD, Ruijin Hospital; Study Chair: Mao Dongliang, Medical PhD, Ruijin Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): August 30, 2020
• Primary Completion (Anticipated): March 30, 2021
• Study Completion (Anticipated): August 30, 2023

Study Registration Dates

• First Submitted: July 31, 2020
• First Submitted That Met QC Criteria: August 11, 2020
• First Posted (Actual): August 14, 2020

Study Record Updates

• Last Update Posted (Actual): August 14, 2020
• Last Update Submitted That Met QC Criteria: August 11, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplastic Processes; Colorectal Neoplasms; Neoplasm Metastasis
• Other Study ID Numbers: RJBY_anti-CEA CAR-T_CRC01

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