A Clinical Research of CAR T Cells Targeting EpCAM Positive Cancer

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Clinical Research of CAR T Cells Targeting EpCAM Positive Cancer

Conditions
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Colon Cancer, Esophageal Carcinoma, Pancreatic Cancer, Prostate Cancer, Gastric Cancer, Hepatic Carcinoma

Intervention / Treatment
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* Biological: CAR-T cell immunotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory EpCAM positive cancer. KPS > 60. Life expectancy>3 months. Gender unlimited, age from 18 years to 80 years. Assessable lesions with a minimum size of 10mm by CT scan or MRI. 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. No other serious diseases(autoimmune disease, immunodeficiency etc.). Adequate cardiac function (LVEF ≥ 40%). No other tumors. Patients volunteer to participate in the research. Exclusion Criteria: Allergic to cytokines. Uncontrolled active infection. Acute or chronic GVHD. MODS. Treated with T cell inhibitor. HIV affected. Pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAR-T cell immunotherapy<br>Enrolled patients will receive CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at EpCAM antigen by infusion. | Biological: CAR-T cell immunotherapy<br>* This CAR-T cell immunotherapy with a novel specific Chimeric antigen receptor aiming at EpCAM antigen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity profile of the EpCAM targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0 | Observe and handle the toxicity profile of the EpCAM targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0 | up to 24 months | 

Secondary Outcome Measures

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