Phase I/II Trial of Androgen Deprivation, With or Without pTVG-AR, and With or Without T-Cell Checkpoint Blockade, in Patients With Newly Diagnosed, High-Risk Prostate Cancer
The current protocol will examine the use of a plasmid DNA vaccine encoding AR, alone or with T-cell checkpoint blockade, to induce and/or augment therapeutic T-cells following androgen deprivation in patients with newly diagnosed prostate cancer scheduled to undergo prostatectomy. Patients without evidence of metastatic disease, with tissue remaining from a pre-treatment biopsy, and who are being considered for standard treatment by prostatectomy, will be invited to participate and will be on study for up to 15 months.
• Histologically confirmed adenocarcinoma of the prostate
• Patients must be considered candidates for prostatectomy as per standard of care
• High-risk patients for recurrent disease, with high risk defined based on one of the following criteria:
‣ Gleason score 7 and baseline serum prostate specific antigen (PSA) \> 20 ng/mL
⁃ Gleason score \> 7
• Life expectancy of at least 12 months at screening
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate hematologic, renal and liver function as evidenced by the following within 4 weeks of day 1:
‣ Absolute neutrophil count (ANC) \> 1000 / mm3
⁃ HgB \> 9.0 gm/dL independent of transfusion
⁃ Platelets \> 100,000 / mm3
⁃ Creatinine \< 2.0 mg/dL
⁃ Aspartate aminotransferase (AST), Alanine transaminase (ALT) \< 2.5 x institutional upper limit of normal (ULN)
⁃ Total bilirubin \< 2x institutional ULN (NOTE: in subjects with Gilbert's syndrome, if total bilirubin is \>2x ULN, measure direct and indirect bilirubin and if direct bilirubin is within normal range, subject may be eligible)
• No known history of HIV 1 and 2, HTLV-1, or active Hepatitis B or Hepatitis C
• Must have adequate tissue (ten 5µm unstained formalin-fixed paraffin-embedded (FFPE) sections containing prostate cancer) remaining from pre-treatment diagnostic prostate biopsy for research purposes
• Patients must be willing to undergo large-volume blood draws (up to 200mL per time point) for the investigational component of this trial
• For those patients who are sexually active, they must be willing to use barrier contraceptive methods during the period of treatment on this trial
• Patients must be informed of the experimental nature of the study and its potential risks, and must sign an IRB-approved written informed consent form indicating such an
• Ability to comply with all study procedures and willingness to remain supine for 120 minutes during imaging