AzTrials
AzTrials

Metastatic Castration-resistant Prostate CancerPhase 1NCT04227275

A Study of CART-PSMA-TGFβRDN in Patients With Metastatic Castration Resistant Prostate Cancer

A Phase 1 study testing CART-PSMA-TGFβRDN, Cyclophosphamide and Fludarabine in people with Metastatic Castration-resistant Prostate Cancer, run by Tceleron Therapeutics, Inc. at 9 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

Trial summary

Multi-center, open-label, Phase 1 study of the safety, tolerability and feasibility of dosing patients harboring metastatic castration resistant prostate cancer (mCRPC) with genetically modified autologous T cells (CART-PSMA-TGFβRDN cells) engineered to express a chimeric antigen receptor (CAR) capable of recognizing… Read more about this study

Who is it for?
Ages 18 years and older, men only
What is being tested?
CART-PSMA-TGFβRDN, Cyclophosphamide and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
9 sitesUnited States
Study dates
22 Nov 2019to 7 Nov 2022
Phase
Phase 1
Are there results?
None posted in the registry

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

  • Confirmed histologic diagnosis of prostate cancer and have mCRPC, with castrate levels of testosterone (<50 ng/mL)
  • PSA measurable disease per Prostate Working Group 3 (PCWG3) criteria
  • Prior therapies defined as at least 2 prior lines of systemic therapy for prostate cancer, including at least one second generation androgen receptor inhibitor and/or CYP17α inhibitor. At least one line of prior therapy must be in the mCRPC setting
  • Estimated estimated glomerular filtration rate ≥ 60 mL/min by Modification of Diet in Renal Disease criteria
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5x the upper limit of normal (ULN); patients with hepatic metastases ALT and AST ≤ 3.0 x ULN
  • Serum total bilirubin < 1.5 mg/dL unless patient has known Gilbert's Syndrome, then serum bilirubin ≤3 mg/dL
Show all 15Show fewer
  • Serum albumin ≥ 3.0 g/dL
  • Left ventricular ejection fraction (LVEF) ≥ 50%. LVEF assessment must have been performed within 8 weeks of enrollment
  • Hemoglobin ≥ 8 g/dL
  • Absolute neutrophil count ≥ 1000/μL
  • Platelet count ≥ 75,000/μL
  • Patients who have not undergone bilateral orchiectomy must be able to continue gonadotropin-releasing hormone (GnRH) therapy during the study
  • Eastern Cooperative Oncology Group (ECOG) score of 0 or 1
  • Toxicities from any previous therapy must have recovered to Grade 1 or baseline
  • Patients of reproductive potential agree to use of approved highly effective contraceptive methods

Who cannot join

  • Active invasive cancer, other than the proposed cancer included in the study, within 2 years prior to screening, unless treated with curative intent
  • Current treatment with systemic corticosteroids (defined as a dose greater than the equivalent of prednisone 10 mg/day)
  • Active autoimmune disease (including connective tissue disease, uveitis, sarcoidosis, inflammatory bowel disease or multiple sclerosis) or a history of severe autoimmune disease requiring prolonged immunosuppressive therapy (any immunosuppressive therapy within 6 weeks prior to screening visit)
  • Current human immunodeficiency virus (HIV), hepatitis C virus, hepatitis B virus infections; Patients who are hepatitis B core antigen positive, hepatitis B surface antigen negative, should have a quantitative viral load measured; If viral load is undetectable, the patient will not be excluded if hey are able to be treated with anti-viral medication for at least 7 days prior to lymphodepletion until at least 6 months after infusion with viral load and ALT monitoring
  • Active or uncontrolled medical or psychological condition that would preclude participation
  • History of seizure disorder
Show all 15Show fewer
  • Prior allogeneic stem cell transplant
  • Central nervous system malignancy
  • History of severe infusion reaction to monoclonal antibodies or biological therapies, or to study product excipients that would preclude the patient safely receiving CART-PSMA-TGFβRDN cells
  • History of being previously treated with a J591 antibody-based therapy
  • Ferritin levels ≥ 4x the upper limit of normal prior to apheresis or prior to the start of lymphodepleting chemotherapy
  • Active or recent (within the past 6 months prior to apheresis or lymphodepletion) cardiovascular disease, defined as (1) New York Heart Association Class III or IV heart failure, (2) unstable angina, (3) a history of recent (within 6 months) myocardial infarction or sustained (> 30 second) ventricular tachyarrhythmias, or (4) cerebrovascular accident
  • Any active infection currently being treated or any infection within the last 6 weeks that required 7 days or more of IV antibiotics or any active infection within the last 4 weeks that requires use of oral antibiotics. Patients may be eligible once these timeframes elapse and with evidence that the infection has completely resolved
  • Have inadequate venous access for or contraindications for the apheresis procedure
  • Must agree not to participate in a conception process or must agree to a highly effective method of contraception

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • The University of Kansas Hospital

    Kansas City, Kansas, 66160

  • Sarah Cannon Research Insitute

    Nashville, Tennessee, 37203

  • Columbia University Medical Center

    New York, New York, 10032

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Thomas Jefferson University

    Philadelphia, Pennsylvania, 19107

  • University of Pittsburgh Medical Center

    Pittsburgh, Pennsylvania, 15232

  • University of Washington Medical Center

    Seattle, Washington, 98195

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

About this study

Official title: A Phase 1 Open-Label, Multi-Center Study of PSMA Targeted Genetically Modified Chimeric Antigen Receptor T Cells in Patients With Metastatic Castration Resistant Prostate Cancer

Multi-center, open-label, Phase 1 study of the safety, tolerability and feasibility of dosing patients harboring metastatic castration resistant prostate cancer (mCRPC) with genetically modified autologous T cells (CART-PSMA-TGFβRDN cells) engineered to express a chimeric antigen receptor (CAR) capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA) and activating the T cell.

Read the detailed description

This is a Phase 1 single-arm study designed to identify the dose and regimen of CART-PSMA- TGFβRDN cells that can be safely administered intravenously following the lymphodepletion (LD) regimen to patients with metastatic castration resistant prostate cancer (mCRPC). Following Dose Escalation, a Cohort Expansion will enroll patients to further explore the safety and tolerability of the selected dose and schedule.

It is anticipated that up to 50 patients will enroll in this study in both dose escalation and cohort expansion.

Being tested
CART-PSMA-TGFβRDN, Cyclophosphamide, Fludarabine, Anakinra
Keywords
Chimeric Antigen Receptor (CAR), T-cells, Prostate-Specific Membrane Antigen (PSMA), Prostate Cancer
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • CART-PSMA-TGFβRDNBiological

    Intravenous administration of genetically modified autologous T cells engineered to express a protein capable of recognizing the tumor antigen prostate-specific membrane antigen (PSMA), as well as a dominant negative TGFβ receptor

  • CyclophosphamideDrug

    Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-PSMA-TGFβRDN genetically modified T cells

  • FludarabineDrug

    Patients will receive cyclophosphamide and fludarabine lymphodepletion chemotherapy followed by the investigational product, CART-PSMA-TGFβRDN genetically modified T cells

  • AnakinraDrug

    In applicable cohorts, patients will receive anakinra prophylactically starting on the day of administration of investigational product, CART-PSMA-TGFβRDN genetically modified T cells

Study groups in NCT04227275
Study groupRoleWhat they receive
Dose EscalationExperimentalDose escalation of intravenous CART-PSMA-TGFβRDN cells for patients with metastatic castration resistant prostate cancer
Receives: Biological: CART-PSMA-TGFβRDN; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Anakinra

What is being measured

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

  1. Dose Escalation: Dose Identification of CART-PSMA-TGFβRDN

    Incidence of Dose Limiting Toxicity (DLT)

    Measured: Up to 2 years

  2. Cohort Expansion: Safety of CART-PSMA-TGFβRDN

    Percentage of patients experiencing adverse events (AEs), including serious and severe AEs overall, by dose level, and severity grade

    Measured: Up to 2 years

Secondary outcomes (3)

  1. Preliminary efficacy of CART-PSMA-TGFβRDN as assessed by biochemical Objective Response Rate (ORR)

    ORR defined as the proportion of patients with maximal prostate-specific antigen (PSA) decline of greater than or equal to 50% at 12 weeks post infusion

    Measured: Up to 2 years

  2. Feasibility of CART-PSMA-TGFβRDN

    Proportion of patients who did not receive CART-PSMA-TGFβRDN cells

    Measured: Up to 2 years

  3. Peripheral expansion and persistence of CART-PSMA-TGFβRDN

    Quantitative polymerase chain reaction (qPCR)

    Measured: Up to 15 years

Timeline

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

  1. First posted13 Jan 2020
  2. Study start22 Nov 2019
  3. Primary completion7 Nov 2022
  4. Study completion7 Nov 2022

Why it stopped: Based on the safety events and evidence of biologic activity without sustained clinical responses the Sponsor finds the risk/benefit analysis unfavorable for patients and has terminated the study.

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
Not applicable
Intervention model
Sequential
Model description
Sequential dose escalation
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04227275
Sponsor's protocol ID
CART-PSMA-TGFβRDN-02
Status last verified
Aug 2023
First submitted
12 Dec 2019
Last updated
21 Aug 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CART-PSMA-TGFβRDN, Cyclophosphamide and Fludarabine in people with Metastatic Castration-resistant Prostate Cancer, run by Tceleron Therapeutics, Inc. at 9 sites 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 15 inclusion and 15 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: stopped early, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites 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?

The study was stopped early (reason given: Based on the safety events and evidence of biologic activity without sustained clinical responses the Sponsor finds the risk/benefit analysis unfavorable for patients and has terminated the study.). Results are not available in the source record.

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

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Escalation: Dose Identification of CART-PSMA-TGFβRDN (time frame: Up to 2 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 NCT04227275.

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 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in