ADT Increases Naïve T-cell Emigrants from the Thymus. A previous NCI trial (NCT00514072) evaluated naïve T-cell emigrants from the thymus after 3 months of ADT. (Thirty-three patients with biochemically recurrent prostate cancer received ADT on this trial.) T-cell receptor excision circles are detectable byproducts of thymic generation of new T-cells and provide a way to quantify such cells. Naïve CD4 cells are defined by flow cytometry as described in the correlative studies section below. By both measures there was a significant increase in the number of naïve T-cells which potentially can be activated by vaccine. (unpublished) 1.2.5 Combining Androgen Receptor Antagonists with PSA-TRICOM An ongoing clinical trial at the NCI is combining PSA-TRICOM with flutamide, an FDA approved ARA, flutamide in men with non-metastatic CRPC (NCT00450463). Patients are randomized to either PSA-TRICOM with flutamide or flutamide alone. The primary endpoint is TTP as determined by PSA (Bubley criteria) or development of metastatic disease [22]. An interim analysis with about half the patients accrued demonstrated that these 2 agents can be safely combined with minimal toxicity. The interim TTP analysis favored the combination of PSA-TRICOM and flutamide compared to flutamide alone (192 days vs. 108 days) [7]. ( Figure 5) The study is completing accrual at the NCI and the Cancer Institute of New Jersey, but the interim analysis provides a preliminary clinical rationale for the combination of PSA-TRICOM with a modern ARA in chemotherapy-naïve patients with mCRPC. The proposed trial in mCRPC will use metastatic progression as an endpoint, which is a more established therapeutic measure than criteria currently established for non-metastatic disease [23]. Figure 5.