A Clinical Research of CAR T Cells Targeting EpCAM Positive Cancer

Phase 1

• Conditions: Colon Cancer; Esophageal Carcinoma; Gastric Cancer; Hepatic Carcinoma; Pancreatic Cancer; Prostate Cancer
• Interventions: Biological: CAR-T cell immunotherapy

• Registration Number: NCT03013712
• Lead Sponsor: First Affiliated Hospital of Chengdu Medical College

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of EpCAM-specific CAR T Cells infusion for EpCAM positive Cancer.

Detailed Description

This study is being conducted to evaluate the safety and efficacy of Chimeric antigen receptor (CAR) T cells targeting EpCAM in treating patients with EpCAM positive cancer. In the research, the investigators design a novel CAR consists of a EpCAM targeting antibody scFv with two intracellular signaling domains derived from CD3 zeta and CD28. Autologous T cells will be gene-engineered with the CAR gene using a lentivirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. The infusion dose is (1-10)×106 EpCAM-CAR positive T cells/kg, and the specific cells numbers depends on the situation of individual CAR-T cells preparation. The way of infusion is vascular interventional mediated or endoscopy, and the cells perfusion process would lasts 15min to 30min, and the specific time depends on patent's tumor-burdened state. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy.

Study Timeline

• Status Verified: 2017-01
• Study Start: 2017-01
• Study First Submitted: 2017-01-03
• Study First Submitted QC: 2017-01-04
• Last Update Submitted: 2017-01-04
• Study First Posted: 2017-01-06
• Last Update Posted: 2017-01-06
• Primary Completion: 2018-12
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Relapsed or refractory EpCAM positive cancer.

2. KPS > 60.

3. Life expectancy>3 months.

4. Gender unlimited, age from 18 years to 80 years.

5. Assessable lesions with a minimum size of 10mm by CT scan or MRI.

6. Acceptable organ function Hematology:

   • Absolute neutrophil count greater than 800/mm^3 without the support of filgrastim.
   • White blood cell (WBC) (> 2000/mm^3).
   • Platelet count greater than 50,000/mm^3.
   • Hemoglobin greater than 9.0 g/dl.

7. No other serious diseases(autoimmune disease, immunodeficiency etc.).

8. Adequate cardiac function (LVEF ≥ 40%).

9. No other tumors.

10. Patients volunteer to participate in the research.

Exclusion Criteria

1. Allergic to cytokines.
2. Uncontrolled active infection.
3. Acute or chronic GVHD.
4. MODS.
5. Treated with T cell inhibitor.
6. HIV affected.
7. Pregnancy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CAR-T cell immunotherapy	CAR-T cell immunotherapy	Enrolled patients will receive CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at EpCAM antigen by infusion.

Primary Outcome Measures

Name	Time	Method
Toxicity profile of the EpCAM targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0	up to 24 months	Observe and handle the toxicity profile of the EpCAM targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0

Secondary Outcome Measures

Name	Time	Method
Survival time of anti-EpCAM CAR T cells in vivo	up to 24 months	Detect the existence of CAR-T cells in the blood of participants through flow cytometry
Anti-tumor efficacy of CAR-T therapy by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1	up to 24 months	Anti-tumor efficacy of CAR-T therapy for patients with EpCAM positive cancers was assessed by RECIST v1.1

Trial Locations

Locations (1)

IEC of Chengdu Medical College; 🇨🇳 Chendu, China