A Pilot Study of Vaccination With Epitope-Enhanced TARP Peptide and TARP Peptide-Pulsed Dendritic Cells in the Treatment of Stage D0 Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT00972309|
Recruitment Status : Completed
First Posted : September 4, 2009
Results First Posted : October 12, 2022
Last Update Posted : October 12, 2022
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- 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.
- 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.
- 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.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Prostate Specific Antigens Prostate Neoplasms||Biological: T-cell receptor alternate reading frame protein (TARP) peptide vaccine Biological: T-cell receptor alternate reading frame protein (TARP) dendritic cell vaccine||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||41 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of Vaccination With Epitope-Enhanced TARP Peptide and TARP Peptide-Pulsed Dendritic Cells in the Treatment of Stage D0 Prostate Cancer|
|Actual Study Start Date :||May 11, 2009|
|Actual Primary Completion Date :||February 4, 2015|
|Actual Study Completion Date :||February 4, 2015|
Experimental: Cohort 1: T-cell receptor alternate reading frame protein (TARP)
Biological: T-cell receptor alternate reading frame protein (TARP) peptide vaccine
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
Experimental: Cohort: 2 -T-cell receptor alternate reading frame protein (TARP)
TARP dendritic cells
Biological: T-cell receptor alternate reading frame protein (TARP) dendritic cell vaccine
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.
- 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.
- 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.
- PSA Doubling Time (PSADT) Response and Failure [ Time Frame: Weeks 12, 24, 36, and 48 ]PSADT response is defined as: a > 50% increase in calculated PSADT OR a PSADT > 15 months. Participant's whose PSADT is decreased by > 50% will be considered PSADT failures. Week 24 PSADT responders will be allowed to receive an additional dose of T-cell receptor alternate reading frame protein (TARP) peptide vaccine at Week 36.
- Change in Tumor Growth Rate Constant: Pre-versus Post T-cell Receptor Alternate Reading Frame Protein (TARP) Vaccination [ Time Frame: 42-651 days on treatment ]Changes in tumor growth rate constants (g) was calculated from fitting the prostate-specific antigen (PSA) curves to an exponential tumor growth model. Comparison of the median growth rate constant to 75th percentile [upper quartile]) of the estimated g of individual subjects pre- and post-TARP vaccination. The Tumor Growth Rate Constant was calculated using a regression-growth equation: f(t) = exp(-d x t) + exp(g x t) - 1, where exp is the base of the natural logarithm, e = 2.7182…, and f(t) is the PSA measurement at time t in days, normalized to (divided by) the PSA measurement at day 0, the time at which treatment is commenced. Rate constant d (decay, in days-1) represents the exponential decrease/regression rate constant of the PSA signal during therapy. Rate constant g (growth, also in days-1) represents the exponential growth/re-growth rate constant of the tumor during treatment.
- Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). [ 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. ]Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
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|Ages Eligible for Study:||18 Years to 100 Years (Adult, Older Adult)|
|Sexes Eligible for Study:||Male|
|Accepts Healthy Volunteers:||No|
- INCLUSION CRITERIA:
- 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.
- Hemoglobin greater than or equal to 10.0 gm/dL, white blood cell (WBC) greater than or equal to 2,500/mm(3), absolute lymphocyte count (ALC) greater than or equal to 500/mm(3), absolute neutrophil count (ANC) greater than or equal to 1,000/mm(3), platelet count greater than or equal to 100,000/mm(3).
- Prothrombin time (PT)/ partial thromboplastin time (PTT) less than or equal to 1.5 times upper limits of normal (ULN) unless receiving clinically indicated anticoagulant therapy.
- Serum glutamic oxaloacetic transaminase (SGOT)/Serum glutamic pyruvic transaminase (SGPT) < 2.5 times ULN, total bilirubin < 1.5 times ULN, creatinine (Cr) < 1.5 times ULN, estimated glomerular filtration rate (GFR) estimated glomerular filtration rate (eGFR) > 60 ml/min.
- Hepatitis B and C negative, unless the result is consistent with prior vaccination or prior infection with full recovery.
- Human immunodeficiency virus (HIV) negative
- No use of investigational agents within 4 weeks of study enrollment.
- No use of immunosuppressive (cytotoxic chemotherapy, systemic steroids) or immunomodulating agents (including intravenous immune globulin (IVIG) within 8 weeks of study entry. Note: topical and intranasal steroid therapy is permitted.
- No other concurrent anticancer therapy.
- No alternative medications known to alter PSA (e.g. phytoestrogens and saw palmetto). Note: patients receiving medications for urinary symptoms such as Flomax or 5-alpha reductase inhibitors (finasteride and dutasteride) on a chronic stable dose for at least 3 months are allowed.
- No prior prostate cancer vaccines expressing TARP or HLA A2.
- Able to understand and provide Informed Consent.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00972309
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Hoyoung M Maeng, M.D.||National Cancer Institute (NCI)|
Documents provided by Hoyoung M. Maeng, M.D., National Cancer Institute (NCI):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
|Responsible Party:||Hoyoung M. Maeng, M.D., Principal Investigator, National Cancer Institute (NCI)|
|Other Study ID Numbers:||
|First Posted:||September 4, 2009 Key Record Dates|
|Results First Posted:||October 12, 2022|
|Last Update Posted:||October 12, 2022|
|Last Verified:||September 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.|
Statistical Analysis Plan (SAP)
Informed Consent Form (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).|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Epitope-Enhanced TARP Peptide
TARP Peptide-Pulsed Dendritic Cells
Genital Neoplasms, Male
Neoplasms by Site
Genital Diseases, Male
Male Urogenital Diseases
Physiological Effects of Drugs