A Pilot Study of Vaccination With Epitope-Enhanced TARP Peptide and TARP Peptide-Pulsed Dendritic Cells in the Treatment of Stage D0 Prostate Cancer

NCT00972309 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 09013909-C-0139
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• PSA (prostate specific antigen) is a protein found on normal and cancerous prostate cells. Levels of this protein are used to identify men who are at risk for prostate cancer and to monitor responses to treatment in men who have been diagnosed with prostate cancer.
• Research has shown that men who continue to have an elevated PSA level following primary treatment for prostate cancer are at increased risk for cancer progression. Studies have shown that the change in PSA levels over time, or PSA doubling time (PSADT), can be accurate in predicting how quickly the cancer is likely to progress. Individuals with a PSADT of less than 3 months are at extremely high risk for disease progression and death from prostate cancer. Individuals with a PSADT of greater than 15 months have a very low risk of death from prostate cancer.
• T-cell receptor alternate reading frame protein (TARP) is a protein that is found in about 95% of prostate cancers and is known to stimulate the immune system. The TARP prostate cancer vaccine is made from pieces of the TARP protein called peptides and includes peptides that have been modified to make them more effective at stimulating immunity. Although these TARP peptides have been shown to stimulate the immune systems of mice, information is needed to determine if they also stimulate the immune system in humans. Since it is unclear what is the best way to give peptide vaccines, the TARP peptides will be given with substances known to stimulate the immune system or in a vaccine made with the patient s own cells. Objectives:
• To determine the immune systems response to vaccination with TARP peptides.
• To determine the safety and toxicity of TARP peptide vaccination.
• To determine if vaccination with the TARP prostate cancer vaccine can slow down PSADT in men with an intermediate PSADT of 3 to 15 months. Eligibility:
• Males 18 years of age and older who have completed their primary treatment for prostate cancer, have stage D0 disease, are Human leukocyte antigen (HLA) A\*0201 positive and who have a PSADT greater than 3 and less than 15 months. Design:
• Patients will be randomized to one of two treatment arms:
• Arm A will receive the TARP vaccine with other substances that stimulate the immune system.
• Arm B will receive the TARP vaccine that includes a patients own white blood cells.
• First week of study, after screening for eligibility has been completed:
• Day 1: Apheresis procedure to extract white blood cells to test the immune response to the vaccine.
• Day 3: Flu vaccine to allow researchers to determine how well a patients immune system is working.
• Clinic visits in Weeks 3, 6, 9, 12, and 15 for physical examination, blood samples, and administration of the TARP peptide vaccine.
• Physical examination and blood samples only in Weeks 18 and 36.
• Additional blood samples and apheresis procedures in Weeks 24 and 48.
• A 6th dose of TARP peptide vaccine will be administer to those patients who have a response to vaccination at week 24.
• No follow-up or long-term study is associated with this study.

Conditions

Prostate Specific Antigens; Prostate Neoplasms

Keywords

Epitope-Enhanced TARP Peptide; Prostate Cancer; TARP Peptide-Pulsed Dendritic Cells; PSADT; HLA-A*0201

Outcome Measures

Primary Outcomes (3)

• Number of Participants With a Positive Immune Response Following Vaccination Determined by Interferon (IFN) Gamma Enzyme-linked Immunosorbent Spot (ELISpot)

  The number of participants in each arm with positive response determined by 3-fold increase over baseline in the number of positive cells by interferon (IFN) gamma enzyme-linked immunosorbent spot (ELISpot) at week 24. Presence of tumor antigen-specific T cells (positive response) mean the vaccine was able to generate immune response (i.e. immunogenicity) which is a good outcome.

  Week 24

• Grades 1-5 Adverse Events Possibly, Probably, or Definitely Related to Drug

  Adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe, Grade 4 is life-threatening, and Grade 5 is death related to adverse event.

  From date treatment consent signed and continuously through 30 days after last vaccination, approximately 59 months and 16 days for Arm A and 58 months and 24 days for Arm B.

• Number of Participants With an Immunological Response of Chromium 51 (51Cr) Release Measured by Tetramer Staining OR Interferon (IFN)-Gamma Enzyme-linked Immune Absorbent Spot (ELISPOT) Assay

  A three-fold increase over baseline in the number of positive cells by tetramer staining OR Interferon (IFN)-gamma enzyme-linked immune absorbent spot (ELISPOT) assay was considered a positive immunological response.

  Weeks 0, 12, 18 and 24

Secondary Outcomes (2)

• PSA Doubling Time (PSADT) Response and Failure

  Weeks 12, 24, 36, and 48

• Change in Tumor Growth Rate Constant: Pre-versus Post T-cell Receptor Alternate Reading Frame Protein (TARP) Vaccination

  42-651 days on treatment

Other Outcomes (1)

• Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0).

  From date treatment consent signed and continuously through 30 days after last vaccination, approximately 59 months and 16 days for Arm A and 58 months and 24 days for Arm B.

Study Arms (2)

Cohort 1: T-cell receptor alternate reading frame protein (TARP)

EXPERIMENTAL

TARP peptides

Biological: T-cell receptor alternate reading frame protein (TARP) peptide vaccine

Cohort: 2 -T-cell receptor alternate reading frame protein (TARP)

EXPERIMENTAL

TARP dendritic cells

Biological: T-cell receptor alternate reading frame protein (TARP) dendritic cell vaccine

Interventions

T-cell receptor alternate reading frame protein (TARP) peptide vaccine BIOLOGICAL

Will receive an admixture of the wildtype and epitope enhanced TARP peptides emulsified with Montanide ISA 51 VG and granulocyte-macrophage colony-stimulating factor (GM-CSF). TARP peptide will be administered subcutaneously at weeks 3, 6, 9, 12 and 15 for a total of five vaccinations with a booster dose of vaccine at Weeks 48 and 96

Cohort 1: T-cell receptor alternate reading frame protein (TARP)

T-cell receptor alternate reading frame protein (TARP) dendritic cell vaccine BIOLOGICAL

Will receive peptide pulsed dendritic cells administered intradermally in two vaccination sites. TARP pulsed dendritic cells will be administered at weeks 3, 6, 9, 12 and 15 for a total of five vaccinations with a booster dose of vaccine at Weeks 48 and 96.

Cohort: 2 -T-cell receptor alternate reading frame protein (TARP)

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males greater than or equal to 18 years of age with histologically confirmed adenocarcinoma of the prostate.
• Human leukocyte antigen-A (HLA-A)\*201 positive
• Patients must have
• Completed and recovered from all prior definitive therapy (surgery, brachytherapy, cryotherapy or radiotherapy) for the primary tumor, or other definitive-intent local therapy.
• Stage D0 disease with documented biochemical progression documented by a rising prostate-specific antigen (PSA).
• No evidence of metastatic disease by physical examination, computed tomography (CT) scan or bone scan.
• For patients following definitive radiation therapy or cryotherapy: a rise in PSA of \>2ng/mL above the nadir.
• For patients following radical prostatectomy: 2 absolute PSA values \> 0.3 ng/mL
• Non-castrate level of testosterone: greater than or equal to 50 ng/dL (prior androgen deprivation treatment (ADT) allowed; must be greater than or equal to 6 months since last dose of ADT).
• A Pre-Enrollment/Baseline prostate-specific antigen doubling time (PSADT) \> 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
• For patients receiving 5-alpha reductase inhibitors (5ARI) e.g. finasteride or dutasteride, only PSA values obtained after at least 3 months on therapy may be used to calculate PSADT.
• Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-2 or Karnofsky 70-100%
• Life expectancy greater than or equal to 1 year.

You may not qualify if:

• HLA-A\*201 negative
• Patients with an active second malignancy other than adequately treated squamous or basal cell carcinoma of the skin, or superficial bladder carcinoma.
• Patients with active infection.
• Patients with brain, visceral or bony metastatic disease.
• Patients in who live attenuated intranasal influenza vaccine (FluMist) is contraindicated including individuals with asthma or reactive airways disease, cardiovascular or pulmonary disease, chronic metabolic diseases (including diabetes mellitus), renal dysfunction or hemoglobinopathies.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Stern LJ, Wiley DC. Antigenic peptide binding by class I and class II histocompatibility proteins. Behring Inst Mitt. 1994 Jul;(94):1-10. No abstract available.

  PMID: 7998902 BACKGROUND

• Berzofsky JA, Ahlers JD, Belyakov IM. Strategies for designing and optimizing new generation vaccines. Nat Rev Immunol. 2001 Dec;1(3):209-19. doi: 10.1038/35105075.

  PMID: 11905830 BACKGROUND

• Rivoltini L, Squarcina P, Loftus DJ, Castelli C, Tarsini P, Mazzocchi A, Rini F, Viggiano V, Belli F, Parmiani G. A superagonist variant of peptide MART1/Melan A27-35 elicits anti-melanoma CD8+ T cells with enhanced functional characteristics: implication for more effective immunotherapy. Cancer Res. 1999 Jan 15;59(2):301-6.

  PMID: 9927036 BACKGROUND

• Berzofsky JA, Wood LV, Terabe M. Cancer vaccines: 21st century approaches to harnessing an ancient modality to fight cancer. Expert Rev Vaccines. 2013 Oct;12(10):1115-8. doi: 10.1586/14760584.2013.836906. No abstract available.

  PMID: 24124874 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

TARP; Protein Subunit Vaccines

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Vaccines, Acellular; Vaccines, Subunit; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: Dr. Hoyoung Maeng
• Organization: National Cancer Institute

hoyoung.maeng@nih.gov

240-781-3253

Study Officials

• Hoyoung M Maeng, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: September 3, 2009
• First Posted: September 4, 2009
• Study Start: May 11, 2009
• Primary Completion: February 4, 2015
• Study Completion: February 4, 2015
• Last Updated: October 12, 2022
• Results First Posted: October 12, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.
• Access Criteria: Clinical data will be made available via subscription to Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).

Locations

US (1)