A Clinical Research of CAR T Cells Targeting CEA Positive Cancer

A Clinical Research of Chimeric Antigen Receptor(CAR) T Cells Targeting CEA Positive 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: Unknown
• Conditions: Breast Cancer; Gastric Cancer; Colorectal Cancer; Pancreatic Cancer; Lung Cancer
• 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 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 Type: Interventional
• Enrollment (Anticipated): 75
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400000
      • Recruiting
      • Southwest Hospital of Third Millitary Medical University
      • Contact: Cheng Qian, PhD; Phone Number: 008615086883400; Email: cqian8634@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pancreatic cancer; Pancreatic cancer treated with Anti-CEA-CAR T.	Biological: Anti-CEA-CAR T; T cells modified with CEA targeted chimeric antigen receptor.
Other: Lung cancer; Lung 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.
Other: Gastric cancer; Gastric 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.
Other: Breast cancer; Breast 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.
Other: 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 of each patient.	Determine the toxicity profile of the CEA targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.	3 years

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 years
Efficacy of anti-CEA CAR T cells to confirm the ability of CAR T cells to kill CEA positive cancer cells		12 weeks
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: Southwest Hospital, China
• Investigators: Study Chair: Cheng Qian, MD, PhD, Southwest Hospital, China

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: January 25, 2015
• First Submitted That Met QC Criteria: January 28, 2015
• First Posted (Estimate): January 29, 2015

Study Record Updates

• Last Update Posted (Actual): April 25, 2017
• Last Update Submitted That Met QC Criteria: April 24, 2017
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: CAR T; CEA
• Other Study ID Numbers: TMMU-BTC-002