A Phase 1 interventional study of Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes and Cyclophosphamide in Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma and Stage IV Prostate Cancer AJCC v8, sponsored by City of Hope Medical Center. Active, not recruiting at 1 site in United States. Open to male participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-06-02.
Sponsored by City of Hope Medical Center · Phase 1, Interventional, and Treatment
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.
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.
6,370 studies on the registry are indexed under Prostatic Neoplasms; 1,400 are open to participants now.
This study's enrollment of 14 is below the median of 58 across 4,822 interventional studies indexed under Prostatic Neoplasms.
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Documented castration resistant prostate cancer (mCRPC) (Note: castration will be defined by a testosterone \< 50 ng/dL achieved by orchiectomy or luteinizing hormone-releasing hormone [LHRH] agonist/antagonist therapy)
Progression of disease manifest by one of the following means during treatment with at least one advanced androgen targeted therapy (e.g., abiraterone or enzalutamide)
Total serum bilirubin =\< 2.0 mg/dL (to be performed within 42 days of signing the main study consent)
Exclusion Criteria:
Patients may receive lymphodepleting regimen (either standard or modified) including fludarabine IV on days -5 to -3 and cyclophosphamide IV on days -5 to -3 or on days -4 and/or -3. The study PI and the protocol team will choose a chemotherapy regimen, for lymphodepletion prior to the PSCA-CAR T cell infusion (with the exception of cohorts 1 and -1 which will not receive lymphodepletion), based on the research participant's disease type and prior therapies. Patients then receive autologous anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T lymphocytes IV over 10-15 minutes at day 0.
Biological: Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes · Drug: Cyclophosphamide · Drug: Fludarabine · Drug: Fludarabine Phosphate
Given IV
Also known as: Autologous Anti-PSCA(dCH2)BBz-CAR T-cells, Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-cells, PSCA(dCH2)BBzeta-CAR T-cells
Given IV
Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Given IV
Also known as: Fluradosa
Given IV
Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586
Grade 3 Toxicity Profile
Grade 3 toxicity profile as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5 and modified Cytokine Release Syndrome (CRS) grading as applicable post chimeric antigen receptor (CAR) T cell infusion.
Time frame: Up to 32 months
Number of Participants Experiencing a Dose-limiting Toxicity (DLT)
Defined by any grade 3 or NCI CTCAE toxicities and modified CRS grading as applicable.
Time frame: Up to 28 days post treatment
Percent of Participants With CAR T Cells Persistence at Day 28
Persistence is defined as CAR T cells comprising at least 7.5 copies/ug of DNA of total CD3 cells.
Time frame: Days 28 post infusion
Expansion of CAR T Cells
Peak expansion (max log10 copies/ug of genomic deoxyribonucleic acid \[DNA\]) will be described.
Time frame: Up to 28 days post treatment
Percent of Participants Achieving Stable Disease
Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated for response based on Prostate Cancer Working Group 3 (PCWG3) criteria.
Time frame: Up to 1 year post treatment
Percent of Participants Alive at Six Months
Rates and associated 95% exact Clopper and Pearson binomial confidence intervals will be estimated.
Time frame: From CAR T cell infusion to death from any cause or last contact date, assessed up to 6 months
| Milestone | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) |
|---|---|---|---|
| Started | 3 | 6 | 5 |
| Completed | 3 | 6 | 5 |
| Not completed | 0 | 0 | 0 |
Grade 3 toxicity profile as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5 and modified Cytokine Release Syndrome (CRS) grading as applicable post chimeric antigen receptor (CAR) T cell infusion.
| Participants | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) |
|---|---|---|---|
| Anemia : Yes | 2 | 2 | 0 |
| Anemia : No | 1 | 4 | 5 |
| Lymphocyte count decreased : Yes | 1 | 0 | 1 |
| Lymphocyte count decreased : No | 2 | 6 | 4 |
| Fatigue : Yes | 0 | 2 | 0 |
| Fatigue : No | 3 | 4 | 5 |
| Pain : Yes | 0 | 1 | 0 |
| Pain : No | 3 | 5 | 5 |
| Cystitis noninfective : Yes | 0 | 2 | 0 |
| Cystitis noninfective : No | 3 | 4 | 5 |
| Hematuria : Yes | 0 | 1 | 0 |
| Hematuria : No | 3 | 5 | 5 |
| Rash maculo-papular : Yes | 0 | 1 | 0 |
| Rash maculo-papular : No | 3 | 5 | 5 |
Defined by any grade 3 or NCI CTCAE toxicities and modified CRS grading as applicable.
| Participants | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) |
|---|---|---|---|
| Number of Participants Experiencing a Dose-limiting Toxicity (DLT) | 0 | 2 | 0 |
Persistence is defined as CAR T cells comprising at least 7.5 copies/ug of DNA of total CD3 cells.
| Percent of participants | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) |
|---|---|---|---|
| Percent of Participants With CAR T Cells Persistence at Day 28 | 66 (9 to 99) | 66 (22 to 96) | 60 (15 to 95) |
Peak expansion (max log10 copies/ug of genomic deoxyribonucleic acid \[DNA\]) will be described.
| log10 copies/ug of DNA | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) |
|---|---|---|---|
| Expansion of CAR T Cells | 2.1 (1.6 to 2.6) | 3.3 (2.5 to 4.0) | 2.8 (2.3 to 3.4) |
Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated for response based on Prostate Cancer Working Group 3 (PCWG3) criteria.
| percentage of participants | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) |
|---|---|---|---|
| Percent of Participants Achieving Stable Disease | 0 (0 to 71) | 67 (22 to 96) | 60 (15 to 95) |
Rates and associated 95% exact Clopper and Pearson binomial confidence intervals will be estimated.
| Percentage of participants | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) |
|---|---|---|---|
| Percent of Participants Alive at Six Months | 33 (1 to 91) | 67 (22 to 96) | 40 (5 to 85) |
Collected over While on study, up to 3 years. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Dose Level 1 (Starting Dose Level 1) | 3/3 (100%) | 2/3 (66.7%) | 3/3 (100%) |
| Dose Level 2 (Dose Level 1b) | 6/6 (100%) | 2/6 (33.3%) | 6/6 (100%) |
| Dose Level 3 (Dose Level 1d) | 5/5 (100%) | 4/5 (80%) | 5/5 (100%) |
| Event | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) |
|---|---|---|---|
| Generalized edemaGeneral disorders | 1/3 | 0/6 | 0/5 |
| Urinary tract infectionInfections and infestations | 1/3 | 0/6 | 0/5 |
| CRSImmune system disorders | 0/3 | 0/6 | 1/5 |
| SepsisInfections and infestations | 0/3 | 0/6 | 1/5 |
| Pain in extremityMusculoskeletal and connective tissue disorders | 0/3 | 0/6 | 1/5 |
| StrokeNervous system disorders | 0/3 | 0/6 | 1/5 |
| Abdominal painGastrointestinal disorders | 0/3 | 1/6 | 0/5 |
| IleusGastrointestinal disorders | 0/3 | 1/6 | 0/5 |
| Cytomegalovirus infection reactivationInfections and infestations | 0/3 | 1/6 | 0/5 |
| HyponatremiaMetabolism and nutrition disorders | 0/3 | 1/6 | 0/5 |
| Event | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) |
|---|---|---|---|
| AnemiaBlood and lymphatic system disorders | 3/3 | 6/6 | 5/5 |
| ConstipationGastrointestinal disorders | 2/3 | 6/6 | 3/5 |
| NauseaGastrointestinal disorders | 3/3 | 4/6 | 5/5 |
| FatigueGeneral disorders | 2/3 | 6/6 | 4/5 |
| Lymphocyte count decreasedInvestigations | 1/3 | 6/6 | 5/5 |
| Neutrophil count decreasedInvestigations | 0/3 | 6/6 | 5/5 |
| White blood cell decreasedInvestigations | 2/3 | 6/6 | 5/5 |
| HypoalbuminemiaMetabolism and nutrition disorders | 3/3 | 6/6 | 5/5 |
| HypertensionVascular disorders | 3/3 | 6/6 | 5/5 |
| BruisingInjury, poisoning and procedural complications | 1/3 | 5/6 | 2/5 |
| Age, Continuous(years) | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) | Total |
|---|---|---|---|---|
| Median | 62 (59 to 69) | 70 (42 to 73) | 69 (62 to 72) | 69 (42 to 73) |
| Sex: Female, Male(Participants) | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) | Total |
|---|---|---|---|---|
| Female | 0 | 0 | 0 | 0 |
| Male | 3 | 6 | 5 | 14 |
| Race (NIH/OMB)(Participants) | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) | Total |
|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 2 | 2 |
| White | 3 | 6 | 3 | 12 |
| More than one race | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 |
| Region of Enrollment(participants) | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) | Total |
|---|---|---|---|---|
| United States | 3 | 6 | 5 | 14 |
| Baseline PSA (Prostate Specific Antigen)(ng/mL) | Dose Level 1 (Starting Dose Level 1) | Dose Level 2 (Dose Level 1b) | Dose Level 3 (Dose Level 1d) | Total |
|---|---|---|---|---|
| Median | 16.5 (10.7 to 20.4) | 88.0 (11.7 to 590.2) | 235.3 (1.8 to 3260.0) | 88.0 (1.8 to 3260.0) |
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