Sequential Vaccinations in Prostate Cancer Patients

Summary

Background: " Adenocarcinoma of the prostate is the most common cancer diagnosis in American males and follows lung cancer as the leading cause of cancer death. " Vaccine strategies represent a novel therapeutic approach in the treatment for prostate cancer. One potential target for a prostate cancer vaccine is prostatic specific antigen (PSA), due to its restricted expression on prostate cancer and normal prostatic epithelial cells. Objectives: " The primary objective is to determine the impact of granulocyte-macrophage colony stimulating factor (GM-CSF) and recombinant fowlpox granulocyte-macrophage colony stimulating factor (rF-GM-CSF) on the immunologic response in patients treated with these vaccines. " Secondary - to determine the change in prostatic specific antigen (PSA)-specific T cells in patients treated with these vaccines using enzyme linked immunosorbent spot (ELISPOT) assay analysis. " To document any objective anti-tumor responses that may occur. Eligibility: " Patients must have androgen insensitive metastatic prostate cancer. " All patients will have received and progressed on hormonal therapy. " Must have objective evidence of metastasis or relapsing local disease. Therefore, must have a rising PSA and at least one of the following: positive bone scan, palpable disease, or positive imaging studies. " Must have a life expectancy of more than 6 months and Eastern Cooperative Oncology Group (ECOG) status of 0 to 2. "Patients must be human leukocyte antigen serotype within HLA-A A serotype group (HLA-A2+). " Granulocyte count greater than or equal to 1,500/mm\^3, Platelet greater than or equal to 100,000/mm\^3, hemoglobin (Hgb) greater than or equal to 10Gm/dL, Lymphocyte count greater than or equal to 500/mm\^3 ;Bilirubin less than 1.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 2.5x upper limit of normal (ULN),Creatinine Clearance greater than or equal to 60 " No significant cardiac disease, no significant pulmonary disease, no serious inter-current medical illness. Design: " Cohorts three, four and five will provide safety data combining cohort two with rGM-CSF as well as two doses of rFGM-CSF respectively. "This study will be conducted as a small, randomized pilot study to compare the immunologic effects of the above vaccine strategy alone, with recombinant granulocyte-macrophage colony stimulating factor (GM-CSF), or with either of 2 doses of fowlpox-GM-CSF. "This study will consist of 4 randomized arms of 8 patients each, all of whom are HLA-A2+. The maximum accrual to the trial should be 62.

Timeline

Start

2003-05-22

Primary completion

2006-03-07

Completion

2009-06-08

Publications

• Background Correale P, Walmsley K, Nieroda C, Zaremba S, Zhu M, Schlom J, Tsang KY. In vitro generation of human cytotoxic T lymphocytes specific for peptides derived from prostate-specific antigen. J Natl Cancer Inst. 1997 Feb 19;89(4):293-300. doi: 10.1093/jnci/89.4.293.
• Background Vergati M, Cereda V, Madan RA, Gulley JL, Huen NY, Rogers CJ, Hance KW, Arlen PM, Schlom J, Tsang KY. Analysis of circulating regulatory T cells in patients with metastatic prostate cancer pre- versus post-vaccination. Cancer Immunol Immunother. 2011 Feb;60(2):197-206. doi: 10.1007/s00262-010-0927-9. Epub 2010 Oct 26.
• Background Yokokawa J, Cereda V, Remondo C, Gulley JL, Arlen PM, Schlom J, Tsang KY. Enhanced functionality of CD4+CD25(high)FoxP3+ regulatory T cells in the peripheral blood of patients with prostate cancer. Clin Cancer Res. 2008 Feb 15;14(4):1032-40. doi: 10.1158/1078-0432.CCR-07-2056.
• Background Gulley JL, Arlen PM, Madan RA, Tsang KY, Pazdur MP, Skarupa L, Jones JL, Poole DJ, Higgins JP, Hodge JW, Cereda V, Vergati M, Steinberg SM, Halabi S, Jones E, Chen C, Parnes H, Wright JJ, Dahut WL, Schlom J. Immunologic and prognostic factors associated with overall survival employing a poxviral-based PSA vaccine in metastatic castrate-resistant prostate cancer. Cancer Immunol Immunother. 2010 May;59(5):663-74. doi: 10.1007/s00262-009-0782-8. Epub 2009 Nov 5.
• Background Stein WD, Gulley JL, Schlom J, Madan RA, Dahut W, Figg WD, Ning YM, Arlen PM, Price D, Bates SE, Fojo T. Tumor regression and growth rates determined in five intramural NCI prostate cancer trials: the growth rate constant as an indicator of therapeutic efficacy. Clin Cancer Res. 2011 Feb 15;17(4):907-17. doi: 10.1158/1078-0432.CCR-10-1762. Epub 2010 Nov 24.
• Background Smith HA, Maricque BB, Eberhardt J, Petersen B, Gulley JL, Schlom J, McNeel DG. IgG responses to tissue-associated antigens as biomarkers of immunological treatment efficacy. J Biomed Biotechnol. 2011;2011:454861. doi: 10.1155/2011/454861. Epub 2010 Dec 19.
• Background Kim JW, Madan RA, Gulley JL. Initial PSA oscillations precede prolonged stable disease in a patient treated with a therapeutic cancer vaccine. Clin Genitourin Cancer. 2012 Mar;10(1):43-6. doi: 10.1016/j.clgc.2011.09.003. Epub 2011 Oct 21. No abstract available.
• Results Arlen PM, Skarupa L, Pazdur M, Seetharam M, Tsang KY, Grosenbach DW, Feldman J, Poole DJ, Litzinger M, Steinberg SM, Jones E, Chen C, Marte J, Parnes H, Wright J, Dahut W, Schlom J, Gulley JL. Clinical safety of a viral vector based prostate cancer vaccine strategy. J Urol. 2007 Oct;178(4 Pt 1):1515-20. doi: 10.1016/j.juro.2007.05.117. Epub 2007 Aug 16.
• Huang J, Jochems C, Talaie T, Anderson A, Jales A, Tsang KY, Madan RA, Gulley JL, Schlom J. Elevated serum soluble CD40 ligand in cancer patients may play an immunosuppressive role. Blood. 2012 Oct 11;120(15):3030-8. doi: 10.1182/blood-2012-05-427799. Epub 2012 Aug 28.

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