Multi-Epitope TARP Peptide Autologous Dendritic Cell Vaccination in Men With Stage D0 Prostate Cancer

Summary

Participation Requirements

Description

TARP T-cell receptor g alternate reading frame protein (TARP) is a 58 amino acid protein expressed by both normal and malignant prostate cancer tissue; 95% of prostate cancer specimens are positive for TARP expression. TARP is highly expressed in prostate cancers of all Gleason types, in primary as ...

TARP T-cell receptor g alternate reading frame protein (TARP) is a 58 amino acid protein expressed by both normal and malignant prostate cancer tissue; 95% of prostate cancer specimens are positive for TARP expression. TARP is highly expressed in prostate cancers of all Gleason types, in primary as well as metastatic disease, and in hormone sensitive and castrate resistant prostate cancer. Therefore, TARP is an ideal tumor antigen target for a vaccine. A prospective, randomized pilot study of 1st generation TARP Peptide vaccination (NCI 09-C-0139) utilizing TARP WT 27-35 and EE29-37-9V peptides was conducted in HLA-A 0201positive men with stage D0 prostate cancer (PSA biochemical recurrence) and a PSA doubling time (PSADT) of greater than or equal to 3 months and less than or equal to 15 months. TARP vaccination was found to be immunogenic, safe and well tolerated, with adverse events limited to injection site reactions less than or equal to Grade 2. TARP vaccination was also associated with a decreased slope log PSA compared to pre-vaccination baseline in 72% of subjects reaching 24 weeks and 74% reaching 48 weeks (p=0.0012 and p=0.0004 for overall changes in slope log PSA, respectively); TARP vaccination also resulted in a 50% decrease in calculated tumor growth rate constant: pre-vaccine g = 0.0042/day, post-vaccine g = 0.0021/day (p=0.003); TARP-specific IFN-g ELISPOT responses were detected in the majority of subjects but did not correlate with decreases in slope log (PSA). Multi-Epitope (ME) TARP Vaccine The vaccine platform includes the original two 9-mer HLA-A*0201 binding TARP peptide epitopes (WT27-35 and EE29-37-9V) utilized in NCI 09-C-0139 as well as an additional five 20-mer TARP peptides overlapping by 10 amino acids for a total of 7 peptides that span the amino acid sequence of the entire TARP protein. The advantage of this multi-epitope TARP peptide vaccine platform is that the overlapping epitopes cover the entire TARP protein, resulting in potential for induction of a multi-valent anti-TARP response. In addition, these longer synthetic peptides include TARP-specific MHC class II CD4+ T cell helper epitopes that will allow generation of better CD8+ T cell responses with improved functional avidity and longevity as well as humoral anti-TARP antibody responses. Study Objectives: Primary: -To assess the difference in the slope log (PSA) for Weeks3-24 minus that formed for the 12 months prior to enrollment on study (referred to as slope324 pre-slope) as well as the slope log (PSA) for weeks 3-48 versus the same pre-treatment slope log (PSA) (referred to as slope 348 preslope) in patients na(SqrRoot) ve to TARP vaccination receiving active, multi-epitope TARP vaccination vs. placebo. Eligibility: Males greater than or equal to 18 years of age with histologically confirmed adenocarcinoma of the prostate. Stage D0 disease with documented biochemical progression documented by rising PSA and no evidence of metastatic disease by physical examination, CT scan or bone scan. PSADT greater than or equal to 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. Performance Status: ECOG 0-1. No other concurrent anticancer therapy or prior prostate cancer vaccines expressing TARP. Study Design: Phase II, prospective, single-blinded, randomized, placebo controlled study of 96 weeks duration in men with Stage D0 prostate cancer. Men with a PSADT greater than or equal to 3 months and less than or equal to 15 months will be randomized 2:1 to receive ME TARP autologous DC vaccination or a control eleutriated monocyte vaccine placebo. An initial lead-in of 6 patientswill be enrolled to allow preliminary assessment of the safety of the ME TARP vaccine platform through 12 weeks before enrollment of prospectively randomized subjects blinded to treatment assignment begins. All patients will receive a total of 6 doses of vaccine (20 x10(6) viable cells/dose) delivered intradermally at Weeks 3, 6, 9, 12, 15, and 24. All patients will undergo a 15-18L apheresis at Week 0 and restaging at Weeks 48 and 96 to confirm maintenance of Stage D0 disease. Sample size: N = 72 (6 lead-in patients for safety assessment, 2:1 randomization: TARP N = 44; placebo N =22).

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