Bethesda, Maryland 20892

  • Prostate Cancer


RATIONALE: Vaccines made from peptides may help the body build an effective immune response to kill tumor cells. It is not yet known whether vaccines are more effective with or without dendritic cells in treating patients with prostate cancer. PURPOSE: This randomized phase I trial is studying the side effects of vaccine therapy in treating patients with progressive stage D0 prostate cancer.

Study summary:

OBJECTIVES: Primary - Determine the safety and toxicity of TARP peptide vaccination vs TARP peptide-pulsed dendritic cell vaccination in patients with biochemically progressing stage D0 prostate cancer naïve to androgen-deprivation therapy. - Determine the T-lymphocyte immune responses of these patients after treatment with TARP peptide vaccination with Montanide® ISA-51 VG and sargramostim vs autologous dendritic cells, as measured by tetramer staining, IFN-γ ELISPOT, and ^51Cr-release cytotoxic T-lymphocyte assays. Secondary - Determine the effect of TARP peptide vaccination on serum prostate-specific antigen doubling time (PSADT) in these patients. - Correlate TARP tumor expression by in situ hybridization with immunologic reactivity. OUTLINE: Patients are randomized to 1 of 2 treatment arms. - Arm I: Patients receive vaccine comprising wild-type and epitope-enhanced TARP peptides with Montanide® ISA-51 VG and sargramostim subcutaneously on weeks 3, 6, 9, 12, and 15*. - Arm II: Patients receive vaccine comprising autologous, TARP peptide-pulsed dendritic cells intradermally on weeks 3, 6, 9, 12, and 15*. NOTE: *Patients that achieve PSA doubling time (PSADT) response at week 24 (i.e., ≥ 50% increase in calculated PSADT OR a PSADT > 15 months) may receive an additional dose of vaccine on week 36. All patients will receive a booster of vaccine at week 48. Patients undergo PSADT response assessment at baseline and at weeks 12, 24, 36, 48, 60, 72, 84, and 96. Patients undergo apheresis and blood sample collection periodically for biomarker analysis. Samples are analyzed for humoral and cellular immune responses to TARP peptide vaccination (e.g., CD4 and CD8 percent and absolute counts), NKT cells, and antigen-specific T-lymphocyte responses by flow cytometry, tetramer staining, IFN-γ ELISPOT, and ^51Cr-release cytotoxic T-lymphocyte assay.


DISEASE CHARACTERISTICS: - Histologically confirmed adenocarcinoma of the prostate - HLA-A*201-positive disease - Stage D0 disease with biochemical progression documented by a rising PSA - Must have completed all prior definitive therapy (i.e., surgery, brachytherapy, cryotherapy, or radiotherapy) or other definitive-intent local therapy for the primary tumor and recovered - A rise in PSA of > 2 ng/mL above the nadir (per RTOG-ASTRO consensus criteria) for patients underwent definitive radiation therapy or cryotherapy - Two absolute rises in PSA > 0.3 ng/mL (per NCCN guidelines) for patients underwent radical prostatectomy - Baseline prostate-specific antigen doubling time (PSADT) > 3 months and ≤ 15 months - Must have ≥ 3 PSA measurements over ≥ 3 months - The interval between PSA measurements must be ≥ 4 weeks - Non-castrate level of testosterone ≥ 50 ng/dL - Prior androgen-deprivation therapy allowed (must be ≥ 6 months since last dose) - No brain, visceral, or bony metastatic disease by physical examination, CT scan, and bone scan PATIENT CHARACTERISTICS: - ECOG performance status (PS) 0-2 OR Karnofsky PS 70-100% - Life expectancy ≥ 1 year - Hemoglobin ≥ 10.0 g/dL - WBC ≥ 3,000/mm³ - Absolute lymphocyte count ≥ 500/mm³ - ANC ≥ 1,500/mm³ - Platelet count ≥ 100,000/mm³ - PT/PTT ≤ 1.5 times upper limit of normal (ULN) (unless receiving clinically indicated anticoagulant therapy) - SGOT and SGPT ≤ 2.5 times ULN - Total bilirubin < 1.5 times ULN - Creatinine < 1.5 times ULN - Estimated glomerular filtration rate > 60 mL/min - Hepatitis B and C negative (unless result is consistent with prior vaccination or infection with full recovery) - HIV negative - No active infection - No active second malignancy, other than adequately treated squamous cell or basal cell carcinoma of the skin or superficial bladder carcinoma - No contraindication to live attenuated intranasal influenza vaccine (FluMist™) (i.e., asthma or reactive airways disease, cardiovascular or pulmonary disease, chronic metabolic diseases [including diabetes mellitus], renal dysfunction, or hemoglobinopathies) PRIOR CONCURRENT THERAPY: - See Disease Characteristics - More than 8 weeks since prior immunosuppressive (cytotoxic chemotherapy, systemic steroids) or immunomodulating agents, including intravenous immunoglobulins (IVIG) - Topical and intranasal steroid therapy is allowed - More than 4 weeks since prior and no other concurrent investigational agents - More than 14 days since prior and no concurrent systemic steroids - Oral corticosteroids for management of acute allergic reactions or contact hypersensitivity of ≤ 14 days duration allowed - Topical and intranasal steroids allowed - No prior prostate cancer vaccines expressing TARP or HLA-A2 - No concurrent chemotherapy, hormonal therapy, or radiation therapy - No concurrent pharmacologic doses of immune-modulating agents, including IVIG, recombinant cytokines, or growth factors - No concurrent medications used for urinary symptoms, including 5-alpha reductase inhibitors (finasteride or dutasteride) - Medications for urinary symptoms that do not alter 5-alpha reductase inhibitors (e.g., Flomax) are allowed - Must be on chronic stable dose - No concurrent herbal, nutritional, or alternative supplements known to alter PSA (e.g., phytoestrogens and saw palmetto) - No other concurrent anticancer therapy



Primary Contact:

Principal Investigator
Jay A. Berzofsky, MD, PhD
NCI - Vaccine Branch

Backup Contact:


Location Contact:

Bethesda, Maryland 20892
United States

Clinical Trials Office - Warren Grant Magnusen Clinical Center
Phone: 888-NCI-1937

Site Status: Recruiting

Data Source:

Date Processed: November 27, 2022

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