Chimeric Antigen Receptor-Modified T Cells for Breast 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 HER2-CAR-T cell Infusion for advanced HER2 positive breast cancer.

Detailed Description
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By enrolling patients with advanced HER2 positive breast cancer adapted to enrolled criteria, this study will document for the first time the safety and the short and long term efficacy of HER2-CAR-T cell infusion for advanced HER2 positive breast cancer.The CAR consists of a HER-2 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 retrovirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. 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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Chimeric Antigen Receptor-Modified T Cells for HER-2 Positive Recurrent and Metastatic Breast Cancer

Conditions
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Breast Cancer

Intervention / Treatment
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* Biological: HER-2-targeting CAR T Cells infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chemotherapy refractory Her2 positive breast cancer； Relapsed patients after anti-Her2 using antibody or kinase inhibitor therapy； Patients must be 18 years of age or older； Patients must have an ECOG (Eastern Cooperative Oncology Group )performance status of 0-2； Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters: Absolute neutrophil count greater than 1500/mm3. Platelet count greater than 100,000/mm3. Hemoglobin greater than 10g/dl (patients may receive transfusions to meet this parameter). Total bilirubin < 1.5 times upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m(2). Seronegative for HIV antibody. Seronegative for active hepatitis B, and seronegative for hepatitis C antibody. Patients must be willing to practice birth control during and for four months following treatment.NOTE:women of child-bearing age must have evidence of negative pregnancy test. Patients must be willing to sign an informed consent. Exclusion Criteria: 1. Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months of study will be excluded. 2.Patients with any of the follo wing pulmonary function abnormalities will be excluded: FEV(forced expiratory volume), < 30% predicted; DLCO (diffusing capacity of lung for carbon monoxide) < 30% predicted (post-bronchodilator); Oxygen Saturation less than 90% on room air. 3.Patients with severe liver and kidney dysfunction or consciousness disorders will be excluded. 4.Pregnant and/or lactating women will be excluded. 5.Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors. 6.Patients with any type of primary immunodeficiencies will be excluded from the study. 7.Patients requiring corticosteroids (other than inhaled) will be excluded. 8.Patients with history of T cell tumors will be excluded. 9.Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.

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

Sexes Eligible for Study
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Female

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HER2-CAR-T<br>In interventional studies, participants are assigned to accept HER-2-targeting CAR T Cells infusion so that researchers can evaluate the effects and safety of the CAR-T cell. | Biological: HER-2-targeting CAR T Cells infusion<br>* HER-2-targeting CAR t cells infusion in breast cancer<br>|
| No Intervention: No Intervention<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with Adverse events |  | 24weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tumor load | Tumor load will be quantified with radiology, bone marrow and/or blood | 24weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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breast cancer, HER2, CAR-T cell