Trial Information

Phase I Trial of Adenovirus- Mediated IL-12 Gene Transduction in Patients With Radiorecurrent Prostate Cancer

Patients with radiorecurrent prostate cancer have few viable treatment options, both in
terms of efficacy and morbidity. Local therapies fail even in highly selected patients due
to locally advanced disease, microscopic metastases, and a worsening of the biology of
cancer cells. Furthermore, attempts at salvage local treatments have the complications of
incontinence, impotence and in some cases unremitting penile pain. Pre-clinical studies in a
mouse model of prostate cancer have noted the potential benefit of adenovirus-mediated gene
therapy to deliver IL-12 in this clinical scenario. This treatment was able to significantly
growth suppress the injected tumor to prolong survival and reduce the number of
pre-established metastases. The mechanisms underlying this activity involved both innate
immunity (neutrophils and natural killer [NK] cells) and acquired immunity ( T cells) and
enhanced expression of Fas to further sensitize Fas/Fas ligand (FasL) killing.

This is a Phase I study. Therefore, the primary objective is finding the Maximum Tolerated
Dose. Within this realm will be monitoring of pro-inflammatory cytokines. Secondary aspects
will involve correlating important mechanisms identified in the pre-clinical model:
induction of T cells.