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Castration-Resistant Prostate CarcinomaPhase 1NCT05805371

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

A Phase 1 study testing Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes, Biopsy and Biospecimen Collection in people with Castration-Resistant Prostate Carcinoma and Metastatic Prostate Carcinoma, run by City of Hope Medical Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes, Biopsy and Biospecimen Collection
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
1 siteUnited States
Study dates
9 Oct 2024to 11 Nov 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Men only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)
  • Creatinine clearance of >= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 42 days prior to enrollment)
  • Corrected QT interval (QTc) =< 480 ms
  • Note: to be performed within 28 days prior to day 1 of protocol therapy
  • Cardiac function (12 lead- electrocardiogram [ECG]) without acute abnormalities requiring investigation or intervention (within 42 days prior to enrollment)
  • Seronegative for human immunodeficiency virus (HIV) antigen (Ag)/antibody (Ab) combo, hepatitis C virus (HCV), active hepatitis B virus (HBV) (surface antigen negative), and syphilis (rapid plasma reagin [RPR])
  • If positive, hepatitis C ribonucleic acid (RNA) quantitation must be performed OR
  • If seropositive for HIV, HCV or HBV, nucleic acid quantitation must be performed. Viral load must be undetectable
  • Note infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
  • Meets other institutional and federal requirements for infectious disease titer requirements
  • Note Infectious disease testing to be performed within 28 days prior to day 1 of protocol therapy
  • Agreement by males of childbearing potential to use an effective method of birth control or abstain from heterosexual activity for the course of the study through at least 3 months after the last dose of protocol therapy
  • Childbearing potential defined as not being surgically sterilized

Who cannot join

  • 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
Show all 12Show fewer
  • 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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

United States1 site, 1 recruiting

  • City of Hope Medical Center

    Duarte, California, 91010

    Tanya B. Dorff, 626-218-8231, tdorff@coh.org

    Tanya B. Dorff

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. 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:

  1. 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:

  1. 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.

  1. 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.

Being tested
Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes, Biopsy, Biospecimen Collection, Bone Scan, Computed Tomography
Medical subject headings
Prostatic Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytesBiological

    Also called 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

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo tumor biopsy

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood, stool, and urine sample collection

  • Bone ScanProcedure or surgery

    Also called Bone Scintigraphy

    Undergo bone scan

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • External Beam Radiation TherapyRadiation

    Also called Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy

    Undergo radiation

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis

  • Lymphodepletion TherapyProcedure or surgery

    Also called Lymphodepleting Therapy, Lymphodepletion

    Undergo lymphodepletion

Study groups in NCT05805371
Study groupRoleWhat they receive
Treatment plan I (PSCA CAR T-cells)ExperimentalPatients undergo leukapheresis and lymphodepletion and receive PSCA-CAR T cells IV up to 3 times on study. Patients undergo bone scan, CT scan, tumor biopsy, and collection of blood, stool, and urine samples throughout the trial.
Receives: Biological: Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Procedure: Leukapheresis; Procedure: Lymphodepletion Therapy
Treatment plan II (PSCA CAR T-cells, radiation)ExperimentalPatients undergo leukapheresis, radiation in 2 doses, and lymphodepletion, and receive PSCA-CAR T cells IV up to 3 times on study. Patients undergo bone scan, CT scan, tumor biopsy, and collection of blood, stool, and urine samples throughout the trial.
Receives: Biological: Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Bone Scan; Procedure: Computed Tomography; Radiation: External Beam Radiation Therapy; Procedure: Leukapheresis; Procedure: Lymphodepletion Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence of adverse events

    Dose limiting toxicities (DLTs), cystitis, grade 3 toxicities and the full toxicity profile as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5 and cytokine release syndrome (CRS) and neurotoxicity as assessed by modified CRS grading. The recommended phase 2 dose (RP2D) will be based on the treatment plan 2 toxicity, activity and correlative data. Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated for DLTs within the DLT period. Tables will be created to summarize all toxicities and side effects by attribution to treatment arm, dose, organ and severity.

    Measured: Post chimeric antigen receptor (CAR) T cell infusion up to 15 years

  2. 50% prostate specific antigen (PSA) level reduction

    Statistical and graphical methods will be used to describe cytokine levels (peripheral blood) and PSA levels over the study period.

    Measured: From baseline measurement up to 1 year post study treatment

Secondary outcomes (9)

  1. Persistence of CAR T cells

    Maximum persistence (in days) will be described by treatment plan, recognizing the number of CAR T cycles the participant received.

    Measured: Up to 28 days post last study treatment

  2. Expansion of CAR T cells

    Peak expansion (log10 copies/ug of genomic deoxyribonucleic acid [DNA]) will be described by treatment plan, recognizing the number of CAR T cycles the participant received.

    Measured: Up to 28 days post last study treatment

  3. PSCA tumor expression

    PSCA expression on tumor cells by IHC and/or flow cytometry.

    Measured: From baseline to end of cycle 1 (Cycle length is 56 days)

  4. Serum cytokine profile

    Statistical and graphical methods will be used.

    Measured: Before CAR T cell infusion through completion of cycle 2, up to 4 months (Cycle length is 56 days)

  5. Overall survival

    Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated.

    Measured: From time of lymphodepletion to date of death, assessed at 1 year

  6. Progression-free survival

    Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated.

    Measured: Survival without radiographic evidence of disease progression from time of lymphodepletion to the date of progression or death, assessed at 6 months

  7. Disease response by PSA

    Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated.

    Measured: From baseline up to 1 year post study treatment

  8. Disease response by immune-modified Response Evaluation Criteria in Solid Tumors criteria

    Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated.

    Measured: At baseline, and months 3, 6, 9 and 12

  9. Disease response by Prostate Cancer Working Group criteria

    Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated.

    Measured: At baseline, and months 3, 6, 9 and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Apr 2023
  2. Study start9 Oct 2024
  3. Primary completion11 Nov 2028 (estimated)
  4. Study completion11 Nov 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05805371
Sponsor's protocol ID
22378
Other IDs
NCI-2023-02186, 22378, P30CA033572
Status last verified
Aug 2026
First submitted
24 Mar 2023
Last updated
21 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes, Biopsy and Biospecimen Collection in people with Castration-Resistant Prostate Carcinoma and Metastatic Prostate Carcinoma, run by City of Hope Medical Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 37 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 21 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of adverse events (time frame: Post chimeric antigen receptor (CAR) T cell infusion up to 15 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05805371.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2026.

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