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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00972309
First received: September 3, 2009
Last updated: March 14, 2014
Last verified: November 2013
  Purpose

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.
  • 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 system s 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 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 patient s 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 patient s 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 Intervention Phase
Prostatic Neoplasms
Prostate Specific Antigens
Drug: TARP 29-35 Peptide (Native Peptide)
Drug: TARP 29-37-9V Peptide Epitope Enchanced Peptide
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • 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 Sarg...

Secondary Outcome Measures:
  • Determine the effect of TARP peptide vaccination on serum prostate specific antigen doubling time (PSADT).
  • Determine the effect of TARP peptide vaccination on PSA growth rate and regression rate constants.

Enrollment: 41
Study Start Date: April 2009
Intervention Details:
    Drug: TARP 29-35 Peptide (Native Peptide)
    N/A
    Drug: TARP 29-37-9V Peptide Epitope Enchanced Peptide
    N/A
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Males greater than or equal to 18 years of age with histologically confirmed adenocarcinoma of the prostate.
  • 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 PSA.
  • No evidence of metastatic disease by physical examination, 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 ADT allowed; must be greater than or equal to 6 months since last dose of ADT).
  • A Pre-Enrollment/Baseline 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: 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, WBC greater than or equal to 2,500/mm(3), ALC greater than or equal to 500/mm3, ANC greater than or equal to 1,000/mm(3), platelet count greater than or equal to 100,000/mm(3).
  • PT/PTT less than or equal to 1.5 times ULN unless receiving clinically indicated anticoagulant therapy.
  • SGOT/SGPT < 2.5 times ULN, total bilirubin < 1.5 times ULN, Cr < 1.5 times ULN, estimated GFR (eGFR) > 60 ml/min.
  • Hepatitis B and C negative, unless the result is consistent with prior vaccination or prior infection with full recovery.
  • 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 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.

EXCLUSION CRITERIA:

  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00972309

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Jay A Berzofsky, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00972309     History of Changes
Obsolete Identifiers: NCT00908258
Other Study ID Numbers: 090139, 09-C-0139
Study First Received: September 3, 2009
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Epotope-Enhanced TARP Peptide
Prostate Cancer
TARP Peptide-Pulsed Dendritic Cells
PSADT
HLA-A*0201

Additional relevant MeSH terms:
Neoplasms
Prostatic Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases

ClinicalTrials.gov processed this record on April 17, 2014