Trials / Recruiting

RecruitingNCT05805371

PSCA-Targeting CAR-T Cells Plus or Minus Radiation for the Treatment of Patients With PSCA+ Metastatic Castration-Resistant Prostate Cancer

A Phase 1b Study Evaluating Combinations With PSCA-Targeting Chimeric Antigen Receptor (CAR)-T Cells for Patients With PSCA+ Metastatic Castration-Resistant Prostate Cancer

Status: Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 21 (estimated)

Sponsor: City of Hope Medical Center · Academic / Other
Sex: Male
Age: 18 Years
Healthy volunteers: Not accepted

Summary

This phase Ib trial tests the safety, side effects, and best dose of autologous anti-prostate stem cell antigen (PSCA)-chimeric antigen receptor (CAR)-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes (PSCA-CAR T cells), plus or minus radiation, in treating patients with castration-resistant prostate cancer that has spread from where it first started (primary site) to other places in the body (metastatic). Castration-resistant prostate cancer continues to grow and spread despite the surgical removal of the testes or medical intervention to block androgen production. CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving PSCA-targeting CAR T-cells, with or without radiation, may kill more tumor cells in men with castration-resistant prostate cancer.

Detailed description

PRIMARY OBJECTIVE: I. Assess the feasibility, safety, and activity of lymphodepleting chemotherapy followed by up to 3 cycles of 50M PSCA-CAR T cell immunotherapy per course either alone (treatment plan 1 \[TP1\]) or in combination with metastasis-directed radiation therapy (MDRT) (treatment plan 2 \[TP2\]) in adult patients with metastatic castration-resistant prostate cancer (mCRPC). SECONDARY OBJECTIVES: I. Describe persistence and expansion of CAR T cells in peripheral blood (PB). II. Describe cytokine levels over the study period. III. Estimate disease response rates. IV. Estimate 6-month progression-free survival (PFS) rate. V. Estimate 1-year overall survival (OS) rate. EXPLORATORY OBJECTIVES: I. Describe the immune landscape changes in PB and tumors. II. Describe phenotype of CAR T cells in PB. III. Describe tumor evolution in PB (circulating tumor cells \[CTCs\], circulating cell-free deoxyribonucleic acid \[DNA\] \[cfDNA\]) and tumors. IV. Determine whether urine cytokines and cellularity is predictive of cystitis occurrence/severity. V. Analyze microbial changes in stool associated with CAR T cell therapy. OUTLINE: Patients are assigned to 1 of 2 treatment plans. TREATMENT PLAN I: Patients undergo leukapheresis and lymphodepletion and receive PSCA-CAR T cells intravenously (IV) up to 3 times on study. TREATMENT PLAN II: Patients undergo leukapheresis, radiation in 2 doses, and lymphodepletion, and receive PSCA-CAR T cells IV up to 3 times on study. Patients in both arms undergo bone scan, computed tomography (CT) scan, tumor biopsy, and collection of blood, stool and urine samples throughout the trial.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes	Given IV
PROCEDURE	Biopsy	Undergo tumor biopsy
PROCEDURE	Biospecimen Collection	Undergo blood, stool, and urine sample collection
PROCEDURE	Bone Scan	Undergo bone scan
PROCEDURE	Computed Tomography	Undergo CT scan
RADIATION	External Beam Radiation Therapy	Undergo radiation
PROCEDURE	Leukapheresis	Undergo leukapheresis
PROCEDURE	Lymphodepletion Therapy	Undergo lymphodepletion

Timeline

Start date: 2024-07-19
Primary completion: 2028-11-11
Completion: 2028-11-11
First posted: 2023-04-10
Last updated: 2025-11-19

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT05805371. Inclusion in this directory is not an endorsement.