A Pilot Study of Vaccination With Epitope-Enhanced TARP Peptide and TARP Peptide-Pulsed Dendritic Cells in the Treatment of Stage D0 Prostate Cancer
Condition: Prostate Specific Antigens; Prostate Neoplasms
MeSH terms: Prostatic Neoplasms
Intervention: T-cell receptor alternate reading frame protein (TARP) peptide vaccine; T-cell receptor alternate reading frame protein (TARP) dendritic cell vaccine
Intervention description: 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; 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.
Intervention MeSH terms: Vaccines
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 41.0
Sex: Male
Minimum age: 18 Years
Maximum age: 100 Years
Healthy volunteers: No
Keywords: Epitope-Enhanced TARP Peptide; Prostate Cancer; TARP Peptide-Pulsed Dendritic Cells; PSADT; HLA-A*0201

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.
    

Eligibility criteria:

        -  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.

        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.