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Prostatic NeoplasmsPhase 2NCT02362451

Multi-Epitope TARP Peptide Autologous Dendritic Cell Vaccination in Men With Stage D0 Prostate Cancer

A Phase 2 study testing Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine in people with Prostatic Neoplasms and Prostate Cancer, run by National Cancer Institute (NCI) at 1 site in United States.

Terminated

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

Official record
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Trial summary

Background: Men who continue to have an elevated or rising prostate specific antigen (PSA) level after their primary prostate cancer treatment are at increased risk for their cancer to progress. The time it takes to progress is highly variable. Read more about this study

Who is it for?
Ages 18 years and older, men only
Conditions the study is for
Prostatic Neoplasms, Prostate Cancer
What is being tested?
Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine
Type of treatment
Vaccines
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
7 participants
Where
1 siteUnited States
Study dates
10 Jul 2015to 13 Feb 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

None listed.

Who cannot join

  • Patients with an active second malignancy other than adequately treated squamous or basal cell carcinoma of the skin.
  • Patients with active infection.
  • Patients on immunosuppressive therapy including:
  • Systemic corticosteroid therapy for any reason. Patients receiving inhaled or topical corticosteroids may participate.
  • Other significant or uncontrolled medical illness. Patients with a remote history of asthma or active mild asthma may participate.
  • Patients who, in the opinion of the Principal Investigator, have significant medical or psychosocial problems that warrant exclusion

Trial locations and contacts

1 site in 1 country.

United States1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Randomized, Placebo-Controlled Phase II Study of Multi-Epitope TARP Peptide Autologous Dendritic Cell Vaccination in Men With Stage D0 Prostate Cancer

Background:

  • Men who continue to have an elevated or rising prostate specific antigen (PSA) level after their primary prostate cancer treatment are at increased risk for their cancer to progress. The time it takes to progress is highly variable. One way to predict this progression is based on the change in PSA levels over time. This is called the PSA doubling time (PSADT). Researchers want to test a vaccine on men with Stage D0 prostate cancer. Stage D0 means the PSA has become detectable again or has started to rise after primary treatment, but has not spread to other organs.
Read more

Objectives:

  • To test a vaccines effectiveness on the rate of PSA increase using PSADT and tumor growth rates.

Eligibility:

  • Men with Stage D0 prostate cancer with a PSADT between 3 and 15 months.

Design:

  • Participants will be screened with blood tests, scans, physical exam, and medical history. Their prostate cancer will be confirmed.
  • Participants will undergo apheresis. Blood will be removed with a needle from one arm. A machine will separate the white blood cells. The blood, minus the white cells, will be returned through a needle in the other arm.
  • Participants will have 14 visits. At each visit, they will have a physical exam and blood tests. They will discuss any side effects.
  • Participants will get injections of either the vaccine or placebo at weeks 3, 6, 9, 12, 15, and 24. Both will be made from the participants own cells.
  • Participants will be selected randomly to receive either active vaccine or placebo. For every two participants assigned to active vaccine, one participant will be assigned to placebo vaccine.
  • Participants will get a Vaccine Report Card to to complete after receiving vaccine.
  • The study lasts 96 weeks.
Read the detailed description

TARP

  • T-cell receptor g alternate reading frame protein (TARP) is a 58 amino acid protein expressed by both normal and malignant prostate cancer tissue; 95% of prostate cancer specimens are positive for TARP expression. TARP is highly expressed in prostate cancers of all Gleason types, in primary as well as metastatic disease, and in hormone sensitive and castrate resistant prostate cancer. Therefore, TARP is an ideal tumor antigen target for a vaccine.
  • A prospective, randomized pilot study of 1st generation TARP Peptide vaccination (National Cancer Institute (NCI) 09-C-0139) utilizing TARP WT 27-35 and EE29-37-9V peptides was conducted in human leukocyte antigen serotype within the HLA-A serotype group (HLA-A 0201) positive men with stage D0 prostate cancer (prostate specific antigen (PSA) biochemical recurrence) and a PSA doubling time (PSADT) of greater than or equal to 3 months and less than or equal to 15 months. TARP vaccination was found to be immunogenic, safe and well tolerated, with adverse events limited to injection site reactions less than or equal to Grade 2. TARP vaccination was also associated with a decreased slope log PSA compared to pre-vaccination baseline in 72% of subjects reaching 24 weeks and 74% reaching 48 weeks (p=0.0012 and p=0.0004 for overall changes in slope log PSA, respectively); TARP vaccination also resulted in a 50% decrease in calculated tumor growth rate constant: pre-vaccine g = 0.0042/day, post-vaccine g = 0.0021/day (p=0.003); TARP-specific interferon gamma (IFN-g) enzyme-linked immune absorbent spot (ELISPOT) responses were detected in the majority of subjects but did not correlate with decreases in slope log (PSA).

Multi-Epitope (ME) TARP Vaccine

  • The vaccine platform includes the original two 9-mer HLA-A*0201 binding TARP peptide epitopes (WT27-35 and EE29-37-9V) utilized in NCI 09-C-0139 as well as an additional five 20-mer TARP peptides overlapping by 10 amino acids for a total of 7 peptides that span the amino acid sequence of the entire TARP protein.
  • The advantage of this multi-epitope TARP peptide vaccine platform is that the overlapping epitopes cover the entire TARP protein, resulting in potential for induction of a multi-valent anti-TARP response. In addition, these longer synthetic peptides include TARP-specific major histocompatibility complex (MHC)class II cluster of differentiation 4 (CD4)+ T cell helper epitopes that will allow generation of better cluster of differentiation 8 (CD8)+ T cell responses with improved functional avidity and longevity as well as humoral anti-TARP antibody responses.

Study Objectives:

Primary:

-To assess the difference in the slope log (PSA) for Weeks3-24 minus that formed for the 12 months prior to enrollment on study (referred to as slope324 pre-slope) as well as the slope log (PSA) for weeks 3-48 versus the same pre-treatment slope log (PSA) (referred to as slope 348 preslope) in patients na(SqrRoot) ve to TARP vaccination receiving active, multi-epitope TARP vaccination vs. placebo.

Eligibility:

  • Males greater than or equal to 18 years of age with histologically confirmed adenocarcinoma of the prostate.
  • Stage D0 disease with documented biochemical progression documented by rising PSA and no evidence of metastatic disease by physical examination, computed tomography (CT) scan or bone scan.
  • Prostate specific antigen doubling time (PSADT) greater than or equal to 3 months and less than or equal to 15 months: ----Patients must have greater than or equal to 3 PSA measurements over greater than or equal to 3 months. --- The interval between PSA measurements must be greater than or equal to 4 weeks.
  • Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-1.
  • No other concurrent anticancer therapy or prior prostate cancer vaccines expressing TARP.

Study Design:

  • Phase II, prospective, single-blinded, randomized, placebo controlled study of 96 weeks duration in men with Stage D0 prostate cancer. Men with a PSADT greater than or equal to 3 months and less than or equal to 15 months will be randomized 2:1 to receive multi-epitope (ME) TARP autologous dendritic cell (DC) vaccination or a control eleutriated monocyte vaccine placebo.
  • An initial lead-in of 6 patientswill be enrolled to allow preliminary assessment of the safety of the ME TARP vaccine platform through 12 weeks before enrollment of prospectively randomized subjects blinded to treatment assignment begins.
  • All patients will receive a total of 6 doses of vaccine (20 x10(6) viable cells/dose) delivered intradermally at Weeks 3, 6, 9, 12, 15, and 24. All patients will undergo a 15-18L apheresis at Week 0 and restaging at Weeks 48 and 96 to confirm maintenance of Stage D0 disease.

Sample size: N = 72 (6 lead-in patients for safety assessment, 2:1 randomization: TARP N = 44; placebo N =22).

Being tested
Autologus elutriated monocyte placebo vaccine, Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine
Keywords
Dendritic Cell Vaccine, Multi Epitope Tarp Peptide, Autolougous Dendritic Cell, D0 Prostate Cancer, Vaccine Therapy
Medical subject headings
Prostatic Neoplasms

What participants receive

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

  • Autologus elutriated monocyte placebo vaccineBiological

    20x10^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24

  • Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccineBiological

    20x10^6 viable cells/dose at weeks 3, 6, 9, 12, 15 and 24

Study groups in NCT02362451
Study groupRoleWhat they receive
1/Lead-in T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine TreatmentExperimentalAll patients to receive autologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine before randomization
Receives: Biological: Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine
2/Active T-cell Receptor g Alternate Reading Frame Protein Dendritic Cell (DC) Vaccine TreatmentExperimentalAutologous multi-epitope T-cell receptor g alternate reading frame protein (TARP) DC vaccine after randomization
Receives: Biological: Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine
3/PlaceboPlacebo comparatorAutologous elutriated monocyte vaccine placebo after randomization
Receives: Biological: Autologus elutriated monocyte placebo vaccine

What is being measured

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

  1. Change in the Slope Log of Prostate-specific Antigen Pre vs Post Treatment

    PSA Doubling Time (PSADT) and slope log (PSA) were calculated at every study visit using the PSADT Memorial Sloane Kettering nomogram. The values were calculated to demonstrate the rate of rise of PSA, expressed as the velocity in nanograms/mL/year, or the PSA doubling time, in months or years. PSA is a tumor marker for prostate cancer and after surgery (undetectable - e.g. <0.2 ng/mL) or radiation PSA should fall to a very low level when the disease is effectively treated. When PSA increases (>2.0 ng/mL) after surgery or radiation that could mean recurrence of the disease. If prostate cancer is growing slower or shrinking after the treatment, PSADT can be longer while PSA slope log is shorter as tumor will make less PSA.

    Measured: One year pre-enrollment; weeks 3-24, and 3 - 48 post vaccine

Secondary outcomes (1)
  1. Progression Free Survival (PFS)

    PFS is defined as the duration of time from start of vaccine treatment to time of progression or death. Given the study population in biochemically recurrent prostate cancer, progression is defined as 1)"radiographic progression" by computed tomography (CT) or bone scan, 2) prostate-specific antigen doubling time (PSADT) that is 3 month or shorter, 3) PSADT decrease 50% or more compared to enrollment PSADT.

    Measured: Week 96 after initial vaccination

Timeline

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

  1. First posted13 Feb 2015 (estimated)
  2. Study start10 Jul 2015
  3. Primary completion13 Feb 2020
  4. Study completion13 Feb 2020

Why it stopped: Slow accrual.

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
7 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02362451
Sponsor's protocol ID
150075
Other IDs
15-C-0075
Status last verified
Mar 2022
First submitted
12 Feb 2015
Last updated
18 Mar 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: All IPD recorded in the medical record will be shared with intramural investigators upon request. All collected individual participant data (IPD) will be shared with collaborators under the terms of collaborative agreements.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Multi-epitope (ME) T-cell receptor g alternate reading frame protein (TARP) vaccine in people with Prostatic Neoplasms and Prostate Cancer, run by National Cancer Institute (NCI) at 1 site 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 0 inclusion and 6 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 18 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Change in the Slope Log of Prostate-specific Antigen Pre vs Post Treatment (time frame: One year pre-enrollment; weeks 3-24, and 3 - 48 post vaccine). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 18 Mar 2022.

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