Clinical Trial: NCT03873805 - My Cancer Genome

NCT03873805

Description:

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.

Related Conditions:

Prostate Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT03873805

Trial Eligibility

Document

Title

Brief Title: PSCA-CAR T Cells in Treating Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer
Official Title: A Phase I Study to Evaluate PSCA-Targeting Chimeric Antigen Receptor (CAR)-T Cells for Patients With PSCA+ Metastatic Castration Resistant Prostate Cancer

Clinical Trial IDs

ORG STUDY ID: 17483
SECONDARY ID: NCI-2019-01264
SECONDARY ID: 17483
NCT ID: NCT03873805

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

Interventions

Drug	Synonyms	Arms
Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes	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	(-)-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	Fluradosa	Treatment (PSCA CAR T cells)
Fludarabine Phosphate	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)

Purpose

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 patients
      with PSCA+ metastatic castration resistant prostate cancer (mCRPC).

      II. Define the recommended phase 2 dose (RP2D) of PSCA-CAR T cells in patients with PSCA+
      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.

Trial Arms

Name	Type	Description	Interventions
Treatment (PSCA CAR T cells)	Experimental	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.	Autologous Anti-PSCA-CAR-4-1BB/TCRzeta-CD19t-expressing T-lymphocytes Cyclophosphamide Fludarabine Fludarabine Phosphate

Eligibility Criteria

        Inclusion Criteria:

          -  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.

          -  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) < 3 x ULN (to be performed within 42 days of signing
             the main study consent)

          -  Alanine aminotransferase (ALT) < 3 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)

          -  Cardiac function (12 lead-electrocardiography [ECG]) (to be performed within 42 days
             of signing the main study consent)

          -  Left ventricular ejection fraction > 40% (to be performed within 42 days of signing
             the main study consent)

          -  Participants of reproductive potential must agree to use acceptable birth control
             methods throughout study therapy and for 3 months after final dose of study treatment

        Exclusion Criteria:

          -  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)

Maximum Eligible Age:	N/A
Minimum Eligible Age:	18 Years
Eligible Gender:	Male
Healthy Volunteers:	No

Primary Outcome Measures

Measure:	Full toxicity profile
Time Frame:	Up to 15 years
Safety Issue:
Description:	Full 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.

Secondary Outcome Measures

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

Measure:	Expansion of CAR T cells
Time Frame:	Up to 1 year post treatment
Safety Issue:
Description:	Peak expansion (max log10 copies/ug of genomic deoxyribonucleic acid [DNA]) will be described.

Measure:	Disease response
Time Frame:	Up to 1 year post treatment
Safety Issue:
Description:	Rates and associated 90% Clopper and Pearson binomial confidence limits will be estimated for response based on Prostate Cancer Working Group 3 (PCWG3) criteria.

Measure:	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
Safety Issue:
Description:	Kaplan Meier methods will be used to estimate median OS, and graph the results.

Measure:	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
Safety Issue:
Description:	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.

Measure:	PSCA expression
Time Frame:	Up to 1 year post treatment
Safety Issue:
Description:	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.

Measure:	Serum cytokine profile
Time Frame:	Up to 1 year post treatment
Safety Issue:
Description:	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.

Details

Phase:	Phase 1
Primary Purpose:	Interventional
Overall Status:	Recruiting
Lead Sponsor:	City of Hope Medical Center

Last Updated

March 10, 2021

Clinical Trials /

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