A Phase I Study of In-Situ, Neoadjuvant, Pre-Radical Prostatectomy RTVP-1 Gene Therapy in Patients With Locally Advanced Adenocarcinoma of the Prostate (SPORE)
The population selected for this study includes patients with locally advanced and/or poorly
differentiated tumors. These patients have an unacceptably high failure rate when treated
by radical prostatectomy alone (over 50% fail within 5 years). The pattern of failure
varies. While some patients present with a local recurrence, many have both a local
recurrence and distant metastases, or just distant metastases. It is reasonable to assume
that many, if not most of these patients, actually harbor micrometastases, present but
undiagnosed clinically, at the time of their radical prostatectomy. Our hypothesis is that
the cytotoxic, proapoptotic, antiangiogenic and immune stimulatory activities of in-situ
RTVP-1 gene therapy will lower the incidence of local tumor recurrences when given to
patients prior to surgery. The second part of our hypothesis is that RTVP-1 gene therapy
will induce a systemic anti-tumor immune response, which will eliminate pre-existing
micrometastases in some of these patients and lower the overall failure rate.
While this Phase I study is not designed to answer these questions, we hope to obtain
mechanistic evidence in support of this hypothesis. A Phase II study will then be proposed
(and properly powered), to study the efficacy of this approach.
Based on our experience with HSV-tk and GCV in-situ gene therapy, it appears that maximal
immune stimulation occurs about 2 weeks following vector injection. Furthermore, repeat
injections of an adenoviral vector do not result in excess toxicity or in the generation of
anti-adenoviral antibodies sufficient to suppress vector activity. We propose here an
intraprostatic injection of RTVP-1 in an adenoviral vector 4-6 weeks prior to radical
prostatectomy, in order to allow full expression of the gene therapy tissue effects.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Assessment of safety/toxicity
After treatment with 3-6 patients per cohort level, the patients will be assessed for the frequency of complications to be assured that they do not exceed those anticipated.
Dov Kadmon, M.D.
Baylor College of Medicine
United States: Food and Drug Administration
|Baylor College of Medicine - Scott Department of Urology||Houston, Texas 77030|