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

Recruiting now · Phase 1

Conditions studied: Castration-Resistant Prostate Carcinoma, Metastatic Prostate Carcinoma, Stage IVB Prostate Cancer AJCC v8

In brief

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.

Key facts

Study ID: NCT05805371
Run by: City of Hope Medical Center
People needed: 21
Starts: 2024-07-19
Expected to finish: 2028-11-11
Last updated by the study team: 2025-11-19

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

Documented informed consent of the participant and/or legally authorized representative (brown)
Assent, when appropriate, will be obtained per institutional guidelines
Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated main consent is processed. However, the research participant is allowed to proceed with lymphodepletion and CAR T cell infusion only after the translated main consent form is signed
Agreement to allow the use of archival tissue from diagnostic tumor biopsies
If unavailable, exceptions may be granted with study principal investigator (PI) approval
Age: >= 18 years
Eastern Cooperative Oncology Group (ECOG) performance status 0-2 or Karnofsky Performance Status (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 the COH Pathology Clinical Trials Specimen Qualification Laboratory (CTSQL)
Fresh or archival biopsy samples may be tested for PSCA expression during screening for eligibility purposes. The results from soft tissue biopsies will be used to confirm eligibility for participants who have a soft-tissue lesion biopsy obtained, but bone biopsy staining results will not impact eligibility since immunohistochemistry (IHC) staining for PSCA has not been optimized in bone specimens. Subjects who undergo bone biopsy on study will be qualified based on the archival tissue result
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 prostate specific antigen (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 CT or bone scan, or soft tissue progression by Response Evaluation Criteria in Solid Tumors (RECIST)
For treatment plan 2, subjects must have at least one and up to 3 metastatic lesions which have not previously been radiated and which is safe for treatment with radiation 16 gray (Gy) in 2 fractions
Fully recovered from the acute toxic effects (except alopecia) to =< grade 1 to prior anti-cancer therapy
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 completed > 14 days prior to leukapheresis
No known contraindications to leukapheresis, steroids or tocilizumab
Absolute neutrophil count (ANC) >= 1,000/mm\^3 (within 42 days prior to enrollment)
NOTE: Growth factor is not permitted within 14 days of ANC assessment
Platelets >= 100,000/mm\^3 (within 42 days prior to enrollment) NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment
Total serum bilirubin =< 2.0 mg/dL (within 42 days prior to enrollment)
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) =< 2.5 x ULN (within 42 days prior to enrollment)
Alanine aminotransferase (ALT) =< 2.5 x ULN (within 42 days prior to enrollment)

You may not qualify if…

Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. Physiologic replacement of steroids (prednisone =< 7.5 mg /day, or hydrocortisone =< 20 mg /day) is allowed
Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening
Subjects 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 to study agent
Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
History of stroke or intracranial hemorrhage within 6 months prior to screening
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
Clinically significant uncontrolled illness
Active infection requiring antibiotics
Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection
Any other condition that would, in the Investigator's judgment, contraindicate the patient'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)

Where it is running

City of Hope Medical Center — Duarte, California, United States (enrolling)

Full record on ClinicalTrials.gov

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