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History of Changes for Study: NCT03873805
PSCA-CAR T Cells in Treating Patients With Metastatic Castration Resistant Prostate Cancer
Latest version (submitted March 17, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 12, 2019 None (earliest Version on record)
2 May 29, 2019 Recruitment Status, Study Status, Study Description, Oversight, Contacts/Locations, Eligibility, Outcome Measures and Conditions
3 December 13, 2019 Study Identification, Study Status, Eligibility, Arms and Interventions, Conditions and Study Description
4 December 23, 2019 Study Status
5 June 26, 2020 Study Status and Study Identification
6 March 8, 2021 Study Status
7 March 17, 2022 Study Status
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Study NCT03873805
Submitted Date:  March 12, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: 17483
Brief Title: PSCA-CAR T Cells in Treating Patients With Metastatic Castration Resistant Prostate Cancer
Official Title: A Phase I Study to Evaluate PSCA-Targeting Chimeric Antigen Receptor (CAR)-T Cells for Patients With Metastatic Castration Resistant Prostate Cancer
Secondary IDs: NCI-2019-01264 [Registry Identifier: CTRP (Clinical Trial Reporting Program)]
17483 [City of Hope Medical Center]
P30CA033572 [U.S. NIH Grant/Contract]
Open or close this module Study Status
Record Verification: March 2019
Overall Status: Not yet recruiting
Study Start: August 1, 2019
Primary Completion: February 21, 2021 [Anticipated]
Study Completion: February 21, 2021 [Anticipated]
First Submitted: March 11, 2019
First Submitted that
Met QC Criteria:
March 12, 2019
First Posted: March 13, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
March 12, 2019
Last Update Posted: March 13, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: City of Hope Medical Center
Responsible Party: Sponsor
Collaborators: National Cancer Institute (NCI)
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: This phase I trial studies side effects and best dose of PSCA-chimeric antigen receptor (CAR) T cells in treating patients with castration resistant prostate cancer that has spread to other places in the body. 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.
Detailed Description:

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 metastatic castration resistant prostate cancer (mCRPC).

II. Define the recommended phase 2 dose (RP2D) of PSCA-CAR T cells in 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.

Open or close this module Conditions
Conditions: Castration Levels of Testosterone
Castration-Resistant Prostate Carcinoma
Metastatic Prostate Carcinoma
PSA Progression
Stage IV Prostate Cancer AJCC v8
Stage IVA Prostate Cancer AJCC v8
Stage IVB Prostate Cancer AJCC v8
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 33 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Treatment (PSCA CAR T cells)
Patients may receive lymphodepleting regimen including fludarabine 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.
Biological: Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes
Given IV
Other Names:
  • 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
Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-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
  • Cyclophosphamidum
  • Cyclophosphan
  • Cyclophosphane
  • Cyclophosphanum
  • Cyclostin
  • Cyclostine
  • Cytophosphan
  • Cytophosphane
  • Cytoxan
  • Fosfaseron
  • Genoxal
  • Genuxal
  • Ledoxina
  • Mitoxan
  • Neosar
  • Revimmune
  • Syklofosfamid
  • WR- 138719
Drug: Fludarabine
Given IV
Other Names:
  • Fluradosa
Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • SH T 586
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Full toxicity profile
[ Time Frame: Up to 15 years ]

Full toxicity profile as assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v)5 post chimeric antigen receptor (CAR) T cell infusion.
2. Dose-limiting toxicity (DLT)
[ Time Frame: Up to 28 days post treatment ]

Defined by any grade 3 or NCI CTCAE toxicities. Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated for DLTs within 28 days of CAR T cell infusion at the recommended phase 2 dose (RP2D)
Secondary Outcome Measures:
1. CAR T cells persistence
[ Time Frame: Up to 1 year post treatment ]

Defined as CAR T cells > 0.1% of total CD3 cells by flow-cytometry. Maximum persistence (in days) will be described.
2. Expansion of CAR T cells
[ Time Frame: Up to 1 year post treatment ]

Peak expansion (max log10 copies/ug of genomic deoxyribonucleic acid [DNA]) will be described.
3. Disease response
[ Time Frame: Up to 1 year post treatment ]

Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated for response based on Prostate Cancer Working Group 3 (PCWG3) criteria.
4. Overall survival (OS)
[ Time Frame: From CAR T cell infusion to the event date (death) or last contact date (censor date), assessed up to 15 years ]

Kaplan Meier methods will be used to estimate median OS, and graph the results.
5. Progression-free survival (PFS)
[ Time Frame: From CAR T cell infusion to event date (progression/relapse or death) the censor date: off protocol therapy date (required disallowed treatment or withdrawal of consent for further therapy) or last contact date, assessed up to 15 years ]

Defined as survival without biochemical (PSA) or radiographic evidence of disease progression or relapse from the date of CAR T cell infusion. Kaplan Meier methods will be used to estimate median PFS, and graph the results.
6. PSCA expression
[ Time Frame: Up to 1 year post treatment ]

PSCA expression on tumor cells by immunohistochemistry (IHC) and/or flow cytometry. Linear regression will be used to assess the relationship between PSCA expression and disease response and toxicities experienced.
7. Serum cytokine profile
[ Time Frame: Up to 1 year post treatment ]

Serum cytokine profile before and after CAR T cell infusion: to assess potential cytokine release syndrome (CRS) toxicity and CAR T cell effector function, sequential serum samples will be analyzed for Th1/Th2 cytokines (e.g., IL-2, IFNgamma, TNFalpha, IL-10, GMCSF, IL-6, MIP-1alpha) by bead array.
Other Outcome Measures:
1. Phenotypes and frequencies of immune cell subsets in the peripheral blood pre- and post-therapy
[ Time Frame: Up to 1 year post treatment ]

Analysis will include CD4:CD8 ratios, differentiation status (CD62L, CD27, CD45 RA/RO), and exhaustion markers (PD1, Tim3, LAG3),trafficking (CCR7, alpha4beta7), proliferation markers (ki67) and effector functions (cytotoxicity, Th1/Th2 cytokines, and CD107a degranulation) on endogenous and CAR+ T cells. Will provide descriptive statistics for exploratory studies.
2. Phenotype of tumor-infiltrating lymphocytes
[ Time Frame: Up to 1 year post treatment ]

Will provide descriptive statistics for exploratory studies.
3. Gene expression
[ Time Frame: Up to 1 year post treatment ]

Assessed by ribonucleic acid sequencing (RNA-seq) of circulating tumor cells (CTCs). Will provide descriptive statistics for exploratory studies.
4. Circulating free DNA (cfDNA) in peripheral blood
[ Time Frame: Up to 1 year post treatment ]

Assessed by whole exome sequencing. Will provide descriptive statistics for exploratory studies.
5. CAR immunogenicity
[ Time Frame: Up to 1 year post treatment ]

Based on the presence of anti-PSCA CAR antibodies or T cell mediated immune responses. Will provide descriptive for statistics exploratory studies.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: Male
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • All subjects 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 Karnofsky performance status (KPS) performance status of 70% or greater
  • 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)
      • Rising PSA documented on 2 occasions at least 7 days apart, with absolute increase > 2 ng/dL despite testosterone < 50
      • 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 3 months must have elapsed since completion of therapy
  • Prior radiotherapy is allowed provided it was not administered to the only evaluable site of disease and was > 14 days prior to screening
  • No known contraindications to leukapheresis, steroids or tocilizumab
  • Total serum bilirubin =< 2.0 mg/dL (to be performed within 42 days prior to day 1 of protocol therapy)
    • 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) < 3 x ULN (to be performed within 42 days prior to day 1 of protocol therapy)
  • Alanine aminotransferase (ALT) < 3 x ULN (to be performed within 42 days prior to day 1 of protocol therapy)
  • Creatinine clearance of >= 50 mL/min per the Cockcroft-Gault formula (to be performed within 42 days prior to day 1 of protocol therapy)
  • If not receiving anticoagulants: International normalized ratio (INR) OR prothrombin (PT) =< 1.5 x ULN (to be performed within 42 days prior to day 1 of protocol therapy). If on anticoagulant therapy: PT must be within therapeutic range of intended use of anticoagulants
  • If not receiving anticoagulants: Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (to be performed within 42 days prior to day 1 of protocol therapy). If on anticoagulant therapy: aPTT must be within therapeutic range of intended use of anticoagulants
  • Cardiac function (12 lead-electrocardiography [ECG]) (to be performed within 42 days prior to day 1 of protocol therapy)
  • Left ventricular ejection fraction > 40% (to be performed within 42 days prior to day 1 of protocol therapy)
  • Pulmonary function tests (diffusing capacity of the lung for carbon monoxide [DLCO] of 40% of best predicted) (to be performed within 42 days prior to day 1 of protocol therapy)
  • Subjects of reproductive potential must agree to use acceptable birth control methods throughout therapy and for 3 months after final study treatment

Exclusion Criteria:

  • Taxane chemotherapy or radium223 within 3 months of study screening
  • Concurrent use of systemic corticosteroids or chronic use of immunosuppressant medications above physiologic replacement doses (prednisone =< 7.5 mg /day, or hydrocortisone =< 20 mg /day is allowed). Recent or current use of inhaled steroids is not exclusionary
  • 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 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 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
  • 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)
Open or close this module Contacts/Locations
Study Officials: Tanya B Dorff
Principal Investigator
City of Hope Medical Center
Locations: United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
Contact:Contact: Tanya B. Dorff 626-218-8231 tdorff@coh.org
Contact:Principal Investigator: Tanya B. Dorff
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations:
Links:
Available IPD/Information:

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