A Clinical Research of CAR T Cells Targeting CEA Positive Cancer

Phase 1

• Conditions: Colorectal Cancer; Lung Cancer; Pancreatic Cancer; Gastric Cancer; Breast Cancer
• Interventions: Biological: Anti-CEA-CAR T

• Registration Number: NCT02349724
• Lead Sponsor: Southwest Hospital, China

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 not yet been fully explored 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, lung cancer, pancreatic cancer, breast cancer and colorectal cancer patients. 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 Timeline

• Study Start: 2014-12
• Study First Submitted: 2015-01-25
• Study First Submitted QC: 2015-01-28
• Study First Posted: 2015-01-29
• Status Verified: 2016-03
• Last Update Submitted: 2017-04-24
• Last Update Posted: 2017-04-25
• Primary Completion: 2018-12
• Study Completion: 2019-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

1. Relapsed or refractory CEA positive lung cancer, pancreatic cancer, gastric cancer, breast cancer and colorectal cancer.
2. KPS>60.
3. Life expectancy>3 months.
4. Gender unlimited, age from 18 years to 80 years.
5. Disease progresses but reserves reaction to recent treatments.
6. Patients who have failed at least one line of a standard treatment.
7. No serious mental disorder.
8. Patients must have adequate cardiac function(no cardiac disease, LVEF≥40% ), adequate pulmonary function as indicated by room air oxygen saturation of >94%, and adequate renal function(Cr≤133umol/L).
9. No other serious diseases(autoimmune disease, immunodeficiency etc.).
10. No other tumors.
11. Patients volunteer to participate in the research.

Exclusion Criteria

1. KPS<50.
2. Patients are allergic to cytokines.
3. MODS.
4. Uncontrolled active infection.
5. Acute or chronic GVHD.
6. Treated with T cell inhibitor.
7. Pregnancy and nursing females.
8. HIV affected.
9. Other situations we think improper for the research.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Breast cancer	Anti-CEA-CAR T	Breast cancer treated with T cells modified with Anti-CEA-CAR T.
Colorectal cancer	Anti-CEA-CAR T	Colorectal cancer treated with T cells modified with Anti-CEA-CAR T.
Lung cancer	Anti-CEA-CAR T	Lung cancer treated with T cells modified with Anti-CEA-CAR T.
Pancreatic cancer	Anti-CEA-CAR T	Pancreatic cancer treated with Anti-CEA-CAR T.
Gastric cancer	Anti-CEA-CAR T	Gastric cancer treated with T cells modified with Anti-CEA-CAR T.

Primary Outcome Measures

Name	Time	Method
Adverse events of each patient.	3 years	Determine the toxicity profile of the CEA targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.

Secondary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) of CEA targeted CAR T cells.	4 weeks	To confirm the maximum tolerated dose of CEA targeted CAR T cells.
Survival time of Anti-CEA CAR T cells in vivo.	3 years	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	12 weeks

Trial Locations

Locations (1)

Southwest Hospital of Third Millitary Medical University; 🇨🇳 Chongqing, Chongqing, China