A Clinical Research of CAR T Cells Targeting HER2 Positive Cancer

Study Overview
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Brief Summary
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Chimeric antigen receptor T cells (CAR-T) therapy has not yet been fully explored in solid tumors. Human epidermal growth factor receptor-2(HER2) is widely expressed in cancers. Investigators have developed anti-HER2 CAR-modified T cells and validated the efficiency targeting HER2-positive cancer in preclinical studies. This study is aimed to confirm its adverse effects including cytokine storm response and any other adverse effects. In addition, CAR-T cells persistence, tumor elimination and disease status after treatment will be evaluated.

Official Title
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A Clinical Research of CAR T Cells Targeting HER2 Positive Cancer

Conditions
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Breast Cancer, Ovarian Cancer, Lung Cancer, Gastric Cancer, Colorectal Cancer, Glioma, Pancreatic Cancer

Intervention / Treatment
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* Biological: Anti-HER2 CAR-T


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Relapsed or refractory HER2 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. Chemistry: Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 3 times the upper limit of normal (patients without liver metastasis) or 6 times the upper limit of normal (patients with liver metastasis). Serum creatinine less or equal to 3 times the upper limit of normal Total bilirubin less than or equal to 3 times the upper limit of normal. 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. Other situations improper for the research.

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: HER2 positive cancers<br>Patients with relapsed and refractory cancer of HER2 expression will be treated with anti-HER2 CAR-T cells | Biological: Anti-HER2 CAR-T<br>* HER-2-targeting CAR-T cells infusion in HER2 positive cancers<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the toxicity profile of the HER2 targeted CAR T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0. | Observe and handle the toxicity profile of the HER2 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-HER2 CAR T cells in vivo. | Detect the existence of CAR-T cells in the blood of participants through qPCR or flow cytometry. | 1 year | 
| Efficacy of anti-HER2 CAR T cells to confirm the ability of CAR T cells to eliminate HER2 positive cancer cells | Evaluate the anti-tumor efficacy of CAR-T therapy by Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 and Immune-Related Response Criteria（iRECIST）. | 12 weeks | 
| Maximum tolerated dose (MTD) of HER2 targeted CAR T cells | Determine the maximum tolerated dose of each participant through the grades of side effects. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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safety, HER2 CAR-T, efficiency, refractory and relapsed cancer