NCT03089203

Brief Summary

This is a single center, single arm Phase I study to establish the safety and feasibility of intravenously administered lentivirally transduced dual PSMA-specific/TGFβ-resistant CAR modified autologous T cells (CART-PSMA-TGFβRDN cells) in patients with metastatic castrate resistant prostate cancer.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
23

participants targeted

Target at P25-P50 for phase_1 prostate-cancer

Timeline
153mo left

Started Mar 2017

Longer than P75 for phase_1 prostate-cancer

Geographic Reach
1 country

1 active site

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress42%
Mar 2017Dec 2038

Study Start

First participant enrolled

March 8, 2017

Completed
12 days until next milestone

First Submitted

Initial submission to the registry

March 20, 2017

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 24, 2017

Completed
21.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 8, 2038

Expected
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 8, 2038

Last Updated

February 23, 2026

Status Verified

February 1, 2026

Enrollment Period

21.5 years

First QC Date

March 20, 2017

Last Update Submit

February 19, 2026

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (3)

  • Occurrence of study related adverse events, laboratory toxicities and clinical events that are possibly, likely, or definitely related to study participation.

    using CTCAE v 4.03

    15 years

  • Clinical feasibility is defined as the frequency of subjects enrolled on this protocol who do not receive CART-PSMA-TGFβRDN cells.

    30 days

  • Manufacturing feasibility is determined by the frequency of product release failures and the occurrence of dose failures (inability to meet target dose).

    30 days

Secondary Outcomes (5)

  • Assess the clinical anti-tumor effect of CART-PSMA-TGFβRDN cells by RECIST

    6 months

  • Assess the clinical anti-tumor effect of CART-PSMA-TGFβRDN cells by PCWG2

    6 months

  • Assess the clinical anti-tumor effect of CART-PSMA-TGFβRDN cells by serum PSA measurement

    6 months

  • Assess the clinical anti-tumor effect of CART-PSMA-TGFβRDN cells by overal survival (OS).

    15 Years

  • Assess the clinical anti-tumor effect of CART-PSMA-TGFβRDN cells by number of subjects with progression free survival (PFS).

    15 Years

Study Arms (5)

Cohort 1

EXPERIMENTAL

CART-PSMA-TGFβRDN cells 1-3x10\^7 Day 0

Biological: CART-PSMA-TGFβRDN cells

Cohort 2

EXPERIMENTAL

CART-PSMA-TGFβRDN cells 1-3x10\^8 Day 0

Biological: CART-PSMA-TGFβRDN cells

Cohort -3

EXPERIMENTAL

CART-PSMA-TGFβRDN cells 1-3x10\^7 Day 0

Biological: CART-PSMA-TGFβRDN cellsDrug: CyclophosphamideDrug: Fludarabine

Cohort 4

EXPERIMENTAL

CART-PSMA-TGFβRDN cells 0.70-1.00 x 10\^8 Day 0

Biological: CART-PSMA-TGFβRDN cellsDrug: CyclophosphamideDrug: Fludarabine

Cohort 3

EXPERIMENTAL

CART-PSMA-TGFβRDN cells at the MTD (established by Cohorts 1-2) on day 0

Biological: CART-PSMA-TGFβRDN cellsDrug: CyclophosphamideDrug: Fludarabine

Interventions

CART-PSMA-TGFβRDN cellsBIOLOGICAL

autologous CAR T cells

Cohort -3Cohort 1Cohort 2Cohort 3Cohort 4
CyclophosphamideDRUG

300 mg/m2/day given over 3 days

Cohort -3Cohort 3Cohort 4
FludarabineDRUG

30 mg/m2/day given over 3 days

Cohort -3Cohort 3Cohort 4

Eligibility Criteria

Age18 Years+
Sexmale(Gender-based eligibility)
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Metastatic castrate resistant prostate cancer
  • RETIRED WITH PROTOCOL VERSION 15
  • Radiographic evidence of osseous metastatic disease and/or measurable, non-osseous metastatic disease (nodal or visceral)
  • Patients ≥ 18 years of age
  • ECOG performance status of 0 - 1
  • Adequate organ function, as defined by:
  • Serum creatinine ≤ 1.5 mg/dl or creatinine clearance ≥ 60 cc/min
  • Serum total bilirubin \< 1.5x ULN
  • Serum ALT/AST \< 2x ULN
  • Adequate hematologic reserve within 4 weeks of eligibility confirmation by physician-investigator as defined by:
  • Hgb \> 10 g/dl
  • PLT \> 100 k/ul
  • ANC \> 1.5 k/ul Note: Subjects must not be transfusion dependent
  • Evidence of progressive castrate resistant prostate adenocarcinoma, as defined by:
  • Castrate levels of testosterone (\< 50 ng/ml) with or without the use of androgen-deprivation therapy AND
  • +5 more criteria

You may not qualify if:

  • RETIRED WITH PROTOCOL V16
  • History of an active non-curative non-prostate primary malignancy within the prior 3 years
  • RETIRED WITH PROTOCOL VERSION 6
  • Subjects who require the chronic use of systemic corticosteroid therapy. Patients may be on a low dose of steroids (≤10mg equivalent of prednisone).
  • RETIRED WITH PROTOCOL V13
  • Subjects with Class III/IV cardiovascular disability according to the New York Heart Association Classification
  • Subjects with symptomatic vertebral metastases affecting spinal cord function (as determined by clinical history, physical exam, or MRI imaging)
  • Active autoimmune disease, including connective tissue disease, uveitis, inflammatory bowel disease, or multiple sclerosis; or a history of severe (as judged by the physician-investigator) autoimmune disease requiring prolonged immunosuppressive therapy
  • Patients with ongoing or active infection.
  • History of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
  • Active hepatitis B, hepatitis C or HIV infection.
  • Active medical condition that, in the opinion of the physician-investigator, would substantially increase the risk of uncontrollable CRS or CAR Neurotoxicity.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

  • Narayan V, Barber-Rotenberg JS, Jung IY, Lacey SF, Rech AJ, Davis MM, Hwang WT, Lal P, Carpenter EL, Maude SL, Plesa G, Vapiwala N, Chew A, Moniak M, Sebro RA, Farwell MD, Marshall A, Gilmore J, Lledo L, Dengel K, Church SE, Hether TD, Xu J, Gohil M, Buckingham TH, Yee SS, Gonzalez VE, Kulikovskaya I, Chen F, Tian L, Tien K, Gladney W, Nobles CL, Raymond HE; Prostate Cancer Cellular Therapy Program Investigators; Hexner EO, Siegel DL, Bushman FD, June CH, Fraietta JA, Haas NB. PSMA-targeting TGFbeta-insensitive armored CAR T cells in metastatic castration-resistant prostate cancer: a phase 1 trial. Nat Med. 2022 Apr;28(4):724-734. doi: 10.1038/s41591-022-01726-1. Epub 2022 Mar 21.

    PMID: 35314843DERIVED

  • Kloss CC, Lee J, Zhang A, Chen F, Melenhorst JJ, Lacey SF, Maus MV, Fraietta JA, Zhao Y, June CH. Dominant-Negative TGF-beta Receptor Enhances PSMA-Targeted Human CAR T Cell Proliferation And Augments Prostate Cancer Eradication. Mol Ther. 2018 Jul 5;26(7):1855-1866. doi: 10.1016/j.ymthe.2018.05.003. Epub 2018 May 8.

    PMID: 29807781DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Cyclophosphamidefludarabine

Condition Hierarchy (Ancestors)

Genital Neoplasms, MaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsGenital Diseases, MaleGenital DiseasesUrogenital DiseasesProstatic DiseasesMale Urogenital Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Naomi Haas, MD

    Universtiy of Pennsylvania

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 20, 2017

First Posted

March 24, 2017

Study Start

March 8, 2017

Primary Completion (Estimated)

September 8, 2038

Study Completion (Estimated)

December 8, 2038

Last Updated

February 23, 2026

Record last verified: 2026-02

Locations

US(1)