Intraperitoneal Infusion of EpCAM CAR-T Cell in Advanced Gastric Cancer With Peritoneal Metastasis (WCH-GC-CART)

Study Overview
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Brief Summary
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To investigate the safety and efficacy of intraperitoneal infusion of EpCAM CAR-T cell in advanced gastric cancer with peritoneal metastasis by a prospective nonrandomized controlled trial.

Detailed Description
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Chimeric antigen receptor modified T (CAR-T) cells have the capability in targeting and recognizing tumor antigen, and can specifically recognize, bind and kill tumor cells with positive antigen. Through local drug delivery, CAR-T cells have successfully achieved remarkable effect to treat solid tumors. Gastric cancer is one of the most frequent malignant tumors with high mortality, especially in China. Peritoneal metastasis is one of the common routes of metastasis. Once peritoneal metastasis occurred, patients should be categorized as clinical pathological stage IV with extremely poor prognosis, and the effect of routine treatments would be unsatisfactory. Epithelial cell adhesion molecule (EpCAM) is highly expressed in gastric cancer cells and closely associated with the poor prognosis of patients. In our previous pre-clinical research researches, the investigators have obtained CAR-T cells targeting EpCAM (EpCAM CAR-T), and finished the preparations of cells which could be used in clinical practice. Based on our previous works, the investigators aim to investigate the safety and efficacy of peritoneal infusion of EpCAM CAR-T cell in advanced gastric cancer with peritoneal metastasis by a prospective nonrandomized controlled trial. The results of this clinical trial are expected to provide the new treatment strategy for gastric cancer patients with peritoneal metastasis.

Official Title
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Clinical Trial of Intraperitoneal CAR-T Cells Infusion for the Treatment of Advanced Gastric Cancer With Peritoneal Metastasis

Conditions
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Neoplasm, Stomach, Metastases, Neoplasm, Neoplasm Seeding

Intervention / Treatment
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* Biological: CAR-T cells targeting EpCAM
* Biological: Chemotherapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with EpCAM positive gastric cancer who have peritoneal metastasis at first visit; Patients with highly suspected or previous proven peritoneal metastasis by biopsy, CT, digital rectal examination, etc. who failed to the routine therapies like chemotherapy; Age between 18 and 75; Estimated survival time is longer than 3 months; Eastern Cooperative Oncology Group (ECOG）scores 0-2; Hemoglobin≥90g/L, ANC≥1.5×109/L, PLT≥80×109/L; Negative pregnancy test for child-bearing period; both male and female patients should agree to apply effective contraceptive methods in the period of treatment and one year after treatment; Both patients and families totally understand the objectives and risks of the treatments and sign the informed consent. Exclusion Criteria: Comorbidity with other diseases treated by immunosuppressive drugs or steroids therapy systematically; Uncontrolled active infection; HIV positive; Active hepatic B or C virus infection, active tuberculosis; Pregnant or lactation female; Disagree to apply effective contraceptive methods in the period of treatment and one year after treatment; Positive cytology examination alone.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CAR-T cell and chemotherapy<br>Biological: CAR-T cells targeting EpCAM Chemotherapy: determined by medical Oncologist | Biological: CAR-T cells targeting EpCAM<br>* Biological: CAR-T cells targeting EpCAM<br>Biological: Chemotherapy<br>* Chemotherapy: determined by medical Oncologist<br>|
| Active Comparator: chemotherapy<br>Chemotherapy: determined by medical Oncologist | Biological: Chemotherapy<br>* Chemotherapy: determined by medical Oncologist<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EpCAM CAR-T cells treatment related adverse events | Adverse events after receiving EpCAM CAR-T cells treatment, according to NCI-CTCAE v4.0. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival outcome | 2-year overall survival rate | 2 years | 
| Metabolism kinetics of CAR-T cells | The level of CAR-T cells will be tested regularly by Real-time Quantitative Polymerase Chain Reaction Detecting System(qPCR) or Flow cytometry. | 2 years | 
| Progress free survival outcome | 2-year progress free survival | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Epithelial Cell Adhesion Molecule, Chimeric Antigen Receptor-modified T cell, Gastric carcinoma, Peritoneal metastasis