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

  • Recruiting
  • Treatment
  • Interventional
  • Non Randomized
  • Biological & Procedure
  • PHASE1
  • City of Hope Medical Center
  • 18 Years -


Study Purpose

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.

Intervention

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


Eligibility Requirements

info icon 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

info icon Agreement to allow the use of archival tissue from diagnostic tumor biopsies * If unavailable, exceptions may be granted with study principal investigator (PI) approval

info icon Age: \>= 18 years

info icon Eastern Cooperative Oncology Group (ECOG) performance status 0-2 or Karnofsky Performance Status (KPS) \>= 70%

info icon 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

info icon Fully recovered from the acute toxic effects (except alopecia) to =\< grade 1 to prior anti-cancer therapy

info icon If there has been prior chemotherapy, at least 2 weeks must have elapsed prior to leukapheresis

info icon Prior radiotherapy is allowed provided it was not administered to the only evaluable site of disease and was completed \> 14 days prior to leukapheresis

info icon No known contraindications to leukapheresis, steroids or tocilizumab

info icon 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

info icon Platelets \>= 100,000/mm\^3 (within 42 days prior to enrollment) NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment

info icon 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

info icon Aspartate aminotransferase (AST) =\< 2.5 x ULN (within 42 days prior to enrollment)

info icon Alanine aminotransferase (ALT) =\< 2.5 x ULN (within 42 days prior to enrollment)

info icon Creatinine clearance of \>= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula (within 42 days prior to enrollment)

info icon Corrected QT interval (QTc) =\< 480 ms * Note: to be performed within 28 days prior to day 1 of protocol therapy

info icon Cardiac function (12 lead- electrocardiogram \[ECG\]) without acute abnormalities requiring investigation or intervention (within 42 days prior to enrollment)

info icon 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

info icon 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

info icon 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

info icon Minimum age: 18

info icon 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

info icon Subjects with clinically significant arrhythmia or arrhythmias not stable on medical management within two weeks of screening

info icon 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

info icon History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent

info icon Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia

info icon History of stroke or intracranial hemorrhage within 6 months prior to screening

info icon 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

info icon Clinically significant uncontrolled illness

info icon Active infection requiring antibiotics

info icon Known history of immunodeficiency virus (HIV) or hepatitis B or hepatitis C infection

info icon 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

info icon 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)

Recruiting status

Recruiting

Estimated enrollment

21

 
Study start date

Jul 19, 2024

Study end date

Nov 11, 2026

Last updated

Mar 22, 2025

Primary purpose

Treatment

Design

Interventional

Intervention

Biological & Procedure

Study phase

PHASE1

Allocation

Non Randomized

 

Sponsor:

City of Hope Medical Center

Collaborator:

National Cancer Institute (NCI)

Investigator:

Tanya B Dorff

NCT05805371

Clinic Location Investigator Distance RECRUITING STATUS Contact