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

NCT03873805 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: 17483NCI-2019-01264
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief 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.

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  Up to 28 days post treatment

Secondary Outcomes (4)

• Percent of Participants With CAR T Cells Persistence at Day 28

  Days 28 post infusion

• Expansion of CAR T Cells

  Up to 28 days post treatment

• Percent of Participants Achieving Stable Disease

  Up to 1 year post treatment

• Percent of Participants Alive at Six Months

  From CAR T cell infusion to death from any cause or last contact date, assessed up to 6 months

Study Arms (1)

Treatment (PSCA CAR T cells)

EXPERIMENTAL

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

Interventions

Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes BIOLOGICAL

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

Treatment (PSCA CAR T cells)

Cyclophosphamide DRUG

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

Treatment (PSCA CAR T cells)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (PSCA CAR T cells)

Fludarabine Phosphate DRUG

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

Treatment (PSCA CAR T cells)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All participants must have the ability to understand and the willingness to sign a written informed consent
• Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 or KPS ≥70%.
• 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)
• Documented PSCA+ tumor expression as evaluated by City of Hope (COH) Pathology Care
• 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)
• Rising PSA documented on 2 occasions at least 7 days apart, with absolute increase \> 2 ng/dL despite testosterone \< 50 OR
• Radiographic evidence of new metastatic foci on computed tomography (CT) or bone scan, or soft tissue progression by Response Evaluation Criteria in Solid Tumors (RECIST)
• Prior chemotherapy with cabazitaxel and/or docetaxel is allowed but not required. If there has been prior chemotherapy, at least 2 weeks must have elapsed prior to leukapheresis
• Prior radiotherapy is allowed provided it was not administered to the only evaluable site of disease and was \> 14 days prior to leukapheresis
• No known contraindications to leukapheresis, steroids or tocilizumab
• Total serum bilirubin =\< 2.0 mg/dL (to be performed within 42 days of signing the main study consent)
• Patients with Gilbert syndrome may be included if their total bilirubin is =\< 3.0 x upper limit of normal (ULN) and direct bilirubin =\< 1.5 x ULN
• Aspartate aminotransferase (AST) \< 5 x ULN (to be performed within 42 days of signing the main study consent)
• Alanine aminotransferase (ALT) \< 5 x ULN (to be performed within 42 days of signing the main study consent)
• Creatinine clearance of \>= 50 mL/min per the Cockcroft-Gault formula (to be performed within 42 days of signing the main study consent)

You may not qualify if:

• Participants with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of signing the main consent
• Participants with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, including seizure disorder
• History of allergic reactions attributed to compounds of similar chemical or biologic composition or other agents used in this study
• Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
• History of stroke or intracranial hemorrhage within 6 months prior to signing the main consent
• History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for \>= 3 years
• Uncontrolled active infection
• Active hepatitis B or hepatitis C infection
• Human immunodeficiency virus (HIV) infection
• Any other condition that would, in the investigator's judgment, contraindicate the subject's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Related Publications (1)

• Dorff TB, Blanchard MS, Adkins LN, Luebbert L, Leggett N, Shishido SN, Macias A, Del Real MM, Dhapola G, Egelston C, Murad JP, Rosa R, Paul J, Chaudhry A, Martirosyan H, Gerdts E, Wagner JR, Stiller T, Tilakawardane D, Pal S, Martinez C, Reiter RE, Budde LE, D'Apuzzo M, Kuhn P, Pachter L, Forman SJ, Priceman SJ. PSCA-CAR T cell therapy in metastatic castration-resistant prostate cancer: a phase 1 trial. Nat Med. 2024 Jun;30(6):1636-1644. doi: 10.1038/s41591-024-02979-8. Epub 2024 Jun 12.

  PMID: 38867077 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Results Point of Contact

• Title: Dr. Tanya Dorff
• Organization: City of Hope Medical Center

tdorff@coh.org

626 218 8231

Study Officials

• Tanya B Dorff

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2019
• First Posted: March 13, 2019
• Study Start: August 20, 2019
• Primary Completion: August 20, 2022
• Study Completion: April 13, 2026
• Last Updated: June 26, 2025
• Results First Posted: October 18, 2023

Record last verified: 2025-06

Locations

US (1)