The purpose of this study is to test the feasibility and safety of in situ gene therapy using non-replicating adenovirus (Ad5)-mediated expression of the sodium-iodide symporter (NIS) gene injected directly into the prostate in patients with locally recurrent prostate cancer following external radiotherapy (EBRT) or permanent prostate brachytherapy (PPB).
Approval for human investigation by the Federal Drug Administration (FDA) and Institutional Review Board (IRB) was obtained for this study. The procedure includes injection of the adenovirus directly into the prostate via a template-guided transperineal route similar to a PPB approach using fluoroscopy and trans-rectal ultrasound image guidance. Viral particles are injected in 5 mL of solution subdivided into equivalent aliquots to 50 separate intraprostatic injection sites. Three days following injection, patients undergo 123I tracer dose imaging with subsequent planned 131I therapy subject to the condition that a prostate dose from 5-20 Gy can be delivered.
In preclinical animal studies, SPECT/CT imaging demonstrated distinct images of the NIS-transduced prostates. In the first eight human subjects treated to the 109 to 1012 viral particle levels, no Grade 2 or greater toxicity has been observed with median 2.1 years (range:0.1 to 6.5 years) of follow up. Dose levels of 109 to 1011 viral particles did not demonstrate 123I tracer uptake sufficient to deliver a therapeutic dose of 131I, whereas 3 of 5 patients receiving 1012 viral particles demonstrated sufficient uptake and received 131I.
Direct injection of non-replicating adenovirus into the prostate in pre-clinical animal and clinical studies has been without significant adverse events. Adequate uptake by the transfected cells expressing the NIS gene has been demonstrated in vivo and meaningful doses of radiation delivered to the prostate in patients receiving 1012 injected viral particles. Patient accrual continues in order to fully evaluate the safety and efficacy of this novel approach in the management of localized radiorecurrent prostate cancer.
Clinical trial identification
All authors have declared no conflicts of interest.