Intervention of Bladder Cancer by CAR-T

Study Overview
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Brief Summary
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This is a Phase I/II and multicenter study designed to evaluate the efficacy and safety of 4SCAR-T cells in participants with locally advanced or metastatic urothelial bladder cancer (UBC) who have no further treatment available.

Official Title
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Intervention of Advanced or Metastatic Urothelial Bladder Cancer by 4SCAR-T Cell Therapies

Conditions
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Bladder Cancer, Urothelial Carcinoma Bladder

Intervention / Treatment
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* Genetic: 4SCAR-PSMA
* Genetic: 4SCAR-FRa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically documented locally advanced or metastatic UBC (including renal pelvis, ureters, urinary bladder, and urethra) Representative tumor specimens as specified by the protocol Adequate hematologic and end organ function Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Life expectancy greater than or equal to (>/=) 12 weeks Measurable disease, as defined by RECIST v1.1 Exclusion Criteria: Any approved anti-cancer therapy within 3 weeks prior to initiation of study treatment Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments Leptomeningeal disease Malignancies other than UBC within 5 years prior to Cycle 1, Day 1 Pregnant and lactating women Significant cardiovascular disease Severe infections within 4 weeks prior to infusion Major surgical procedure other than for diagnosis within 4 weeks History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins; known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation History of autoimmune disease Prior allogeneic stem cell or solid organ transplant History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan Positive test for human immunodeficiency virus (HIV) and/or active hepatitis B or hepatitis C or tuberculosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4SCAR-PSMA<br>4SCAR PSMA-modified T cells can recognize and kill tumor cells through the recognize of PSMA .This study will evaluate the side effects and effective doses of 4SCAR-PSMA T cells in treating refractory and recurrent solid tumors. | Genetic: 4SCAR-PSMA<br>* PSMA-specific 4th Generation CART<br>|
| Experimental: 4SCAR-FRa<br>4SCAR FRa-modified T cells can recognize and kill tumor cells through the recognize of FRa .This study will evaluate the side effects and effective doses of 4SCAR-FRa T cells in treating refractory and recurrent solid tumors. | Genetic: 4SCAR-FRa<br>* FRa-specific 4th Generation CART<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival rate after receiving 4SCART infusion | to determine the efficacy of 4SCAR T cells | 1 year | 
| Using CTCAE 4 standard to evaluate the level of adverse events after receiving 4SCART infusion | to evaluate the level of adverse events with CTCAE 4 | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The expansion and persistence of 4SCAR T cells | The investigators will monitor the expansion and functional persistence of 4SCAR T cells in the peripheral blood of patients and the correlation with antitumor effects | 1 year | 
| Immune responses after infusions | assessment of cytokine profile | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAR T, Bladder