NCT03873805

PSCA-CAR T Cells in Treating Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer

A Phase I Study to Evaluate PSCA-Targeting Chimeric Antigen Receptor (CAR)-T Cells for Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: Male
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies side effects and best dose of PSCA-chimeric antigen receptor (CAR) T cells in treating patients with prostate stem cell antigen positive (PSCA+) castration resistant prostate cancer that has spread to other places in the body (metastatic). PSCA-CAR T cells are immune cells that have been engineered in the laboratory to kill tumor cells. This is done by using a virus to insert a piece of deoxyribonucleic acid (DNA) into the immune cells that allows them to recognize prostate tumor cells. It is not yet known how well PSCA-CAR T cells works in killing tumor cells in patients with metastatic castration resistant prostate cancer.

Detailed description

PRIMARY OBJECTIVES: I. Define the safety and tolerability of autologous anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T lymphocytes (PSCA-CAR T cells) in patients with PSCA+ metastatic castration resistant prostate cancer (mCRPC). II. Define the recommended phase 2 dose (RP2D) of PSCA-CAR T cells in patients with PSCA+ mCRPC. SECONDARY OBJECTIVES: I. Assess the expansion and persistence of PSCA-CAR T cells. II. Assess clinical response based on Prostate Cancer Working Group 3 (PCWG3) criteria. III. Assess survival outcomes (including biochemical progression free survival \[PFS\], radiographic PFS and overall survival \[OS\]). IV. Assess serum cytokine profiles in peripheral blood pre- and post-therapy. V. Describe the PSCA expression level on tumor cells prior to CAR T cell infusion, and the relationship it may have with disease response and observed toxicities. EXPLORATORY OBJECTIVES: I. Characterize the phenotypes and frequencies of immune cell subsets in the peripheral blood pre- and post-therapy. II. Enumerate and characterize tumor-infiltrating lymphocytes (TILs) pre- and post-therapy. III. Enumerate and analyze gene expression of circulating tumor cells (CTC) pre- and post-therapy. IV. Analyze circulating cell-free DNA (cfDNA). V. Determine the immunogenicity of PSCA-CAR T cells. OUTLINE: This is a dose-escalation study. Patients may receive lymphodepleting regimen at the discretion of the treating physician including fludarabine intravenously (IV) on days -5 to -3 and cyclophosphamide IV on days -5 to -3 or on days -4 and/or -3. Patients then receive autologous anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T lymphocytes IV over 10-15 minutes at day 0. After completion of study treatment, patients are followed up at day 1, every 2 days for up to 14 days, weekly for up to 1 month, every month for up to 1 year, and then annually for up to 15 years.

Conditions

• Castration-Resistant Prostate Carcinoma
• Metastatic Prostate Carcinoma
• Stage IV Prostate Cancer AJCC v8
• Stage IVA Prostate Cancer AJCC v8
• Stage IVB Prostate Cancer AJCC v8

Interventions

Type	Name	Description
BIOLOGICAL	Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes	Given IV
DRUG	Cyclophosphamide	Given IV
DRUG	Fludarabine	Given IV
DRUG	Fludarabine Phosphate	Given IV

Timeline

• Start date: 2019-08-20
• Primary completion: 2022-08-20
• Completion: 2026-04-13
• First posted: 2019-03-13
• Last updated: 2025-06-26
• Results posted: 2023-10-18

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study