Trial Information

Phase I Study of Adenoviral Vector Delivery of The IL-12 Gene in Men With Recurrence or Persistent Cancer of the Prostate After Primary Therapy With or Without Metastatic Disease (SPORE)

The development of a clinical trial for gene therapy in prostate cancer will be coordinated
with our collaborators at Baylor involved in similar studies in order to facilitate the
approval process. We have submitted a proposal to the NIH Recombinant DNA Advisory Committee
(RAC) committee for accelerated review. A detailed clinical protocol and informed consent
for a Phase I clinical trial of gene therapy for prostate cancer has been approved by the
Baylor Affiliates Review Board and the FDA.

Human subjects included in this project will be limited to men who have biopsy-proven local
recurrence or persistence of cancer in the prostate gland with or without metastatic disease
after hormone therapy, cryosurgery and/or definitive irradiation therapy. Patients with
biopsy-proven prostate cancer, clinical stages T1-T3, Nx-N1 or M0-M1 are eligible.
Biologically active local recurrence of tumor will be defined as biopsy-proven cancer in the
prostate, at least one year after the completion of radiation therapy, in a patient who has
a rising serum PSA level on at least 3 separate occasions at least 2 weeks apart.

Patients will also be carefully followed to document toxicity, using standard CTEP toxicity
criteria. Responses will be categorized as follows: progressive disease, stable disease,
partial objective response, and complete objective response. Progressive disease will be
defined as a rise in the serum PSA level by 25% in the first 3 months and thereafter, a
positive biopsy in conjunction with an enlarging nodule on digital rectal exam or an
enlarging hypoechoic lesion on ultrasound, or the development of new symptoms clearly
related to the cancer in the presence of a positive biopsy, or the presence on biopsy of
cancer of higher grade or cancer that is more extensive. A complete response will be defined
as a serum PSA level that decreases to less than 1 ng/ml, in combination with a negative
biopsy of the prostate and the absence of symptoms referable to cancer. A partial objective
response would be a PSA level that decreases by at least 50% compared to baseline in
association with a biopsy result that shows clearly diminished or minimum but persistent
cancer cells.

This Phase I study is designed to evaluate the safety of Adv/IL-12 gene therapy with an
intent to offer a potential therapeutic advantage. The potential risks associated with the
use of gene therapy in this group would appear reasonable in so far as evaluations will be
frequent and progression (should it occur) will be found early and allow rapid movement of
the patient to other possible therapies. Effectiveness will be monitored by serum PSA,
transrectal ultrasound of the prostate, prostate biopsy and comparison of survival times to
historical survival times for patients with radiation recurrent prostate tumors. Additional
research laboratory analyses will be performed to evaluate the immune response engendered by
this gene therapy protocol. This will consist of analysis of serum and/or plasma and urine
for systemic cytokine production using standard ELISA methodologies that we have performed
in previous studies. In addition we will collect whole blood for the analysis of T cells by
flow cytometry. We have established protocols for this analysis that can detect total CD4
and CD8 cells as well as those that express markers of activation such as HLA/DR.