NCT00972309CompletedPhase 1
A Pilot Study of Vaccination With Epitope-Enhanced TARP Peptide and TARP Peptide-Pulsed Dendritic Cells in the Treatment of Stage D0 Prostate Cancer
National Cancer Institute (NCI)2 sites in 1 country41 target enrollmentStarted: May 11, 2009Last updated:
Conditions
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 41
- Locations
- 2
- Primary Endpoint
- Grades 1-5 Adverse Events Possibly, Probably, or Definitely Related to Drug
Study Overview
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.
Detailed Description
BACKGROUND:
- T-cell receptor alternate reading frame protein (TARP) is expressed by both normal and malignant prostate cancer tissue and is found in about 95% of prostate cancer specimens. TARP is immunogenic and hence is a target antigen for vaccination.
- The immunogenicity of TARP peptides can be augmented through epitope enhancement that is achieved through amino acid substitutions resulting in increased peptide binding affinity.
- Two HLA-A*0201 TARP peptide epitopes are associated with generation of catalytic T-cell responses: TARP27-35 and TARP29-37. Substitution of Val for Leu at position 9 in TARP29-37, results in a peptide with increased binding affinity (TARP29-37-9V) that induces antigen specific T cells able to recognize wild type and multiple modified TARP peptides. The affinity of the TARP 27-35 peptide, corresponding to a distinct but overlapping epitope, is high enough that no enhancement was required.
- Stage D0 prostate cancer patients have no evidence of visceral or bony metastatic disease but have persistently elevated or rising prostate-specific antigen (PSA) levels (biochemical progression) and are at increased risk for disease progression. Since they lack much of the immune dysfunction associated with the high tumor burden characteristic of end-stage metastatic disease, they are an ideal population in which to study therapeutic vaccination to slow or prevent disease recurrence and progression.
- Dendritic cells (DC) are the most potent antigen-presenting cells of the immune system and are being studied extensively for anti-tumor activity in a broad spectrum of cancer patients.
- As the optimal method for therapeutic immunization with peptide vaccines in patients with cancer is unclear, vaccination with TARP peptides in Montanide ISA 51 VG adjuvant plus Sargramostim will be studied in a randomized fashion with autologous, TARP peptide-pulsed dendritic cells (DCs) in HLA-A*0201 Stage D0 prostate cancer patients.
OBJECTIVES:
- Determine the safety and toxicity of TARP peptide and TARP peptide-pulsed dendritic cell vaccination in patients with Stage D0 prostate cancer.
- Determine the T-lymphocyte immune responses to TARP peptide vaccination with Montanide ISA 51 VG plus Sargramostim or autologous dendritic cells as measured by tetramer staining, interferon (IFN)-gamma enzyme-linked immune absorbent spot (ELISpot) and (51)Cr release cytotoxic T lymphocytes (CTL) assays.
ELIGIBILITY:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 100 Years (Adult, Older Adult)
- Sex
- Male
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Grades 1-5 Adverse Events Possibly, Probably, or Definitely Related to Drug
Time Frame: 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.
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.
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
Time Frame: Weeks 0, 12, 18 and 24
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.
Number of Participants With a Positive Immune Response Following Vaccination Determined by Interferon (IFN) Gamma Enzyme-linked Immunosorbent Spot (ELISpot)
Time Frame: Week 24
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.
Secondary Outcomes
- 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)
Investigators
Hoyoung M. Maeng, M.D.
Principal Investigator
National Cancer Institute (NCI)
Study Sites (2)
Loading locations...
Similar Trials
Completed
Phase 2
Combination Immunotherapy in Biochemically Recurrent Prostate CancerProstate CancerNCT03315871National Cancer Institute (NCI)40
Completed
Phase 2
Vaccine Therapy in Treating Patients With Recurrent Prostate CancerProstate CancerNCT00030602University of Maryland, Baltimore
Completed
Phase 2
Phase II Study of Adenovirus/PSA Vaccine in Men With Hormone - Refractory Prostate CancerHormone Refractory Prostate CancerNCT00583024David M Lubaroff32
Unknown
Phase 1
Peptide-specific Vaccination in HLA-A*02 Positive Patients With Biochemical Recurrence After Radical ProstatectomyRecurrent Prostate CancerNCT02452307University Hospital Tuebingen36
Unknown
Phase 1
Phase 1A/1B Study of PSA/IL-2/GM-CSF Vaccine for Recurrent Prostate Cancer in Hormone Naive and Hormone Independent PatientsProstate CancerNCT02058680OncBioMune Pharmaceuticals48