Phase I - Pre-Radical Prostatectomy RTVP-1 Gene Therapy for Prostate Cancer
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||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)|
- Assessment of safety/toxicity [ Time Frame: 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. ] [ Designated as safety issue: Yes ]
- To collect data on the morphologic and cytotoxic changes in the radical prostatectomy specimen [ Time Frame: Tumor response as measured by cytoreduction is not likely to be the major effect of the treatment. ] [ Designated as safety issue: No ]
|Study Start Date:||August 2006|
|Study Completion Date:||April 2011|
|Primary Completion Date:||April 2011 (Final data collection date for primary outcome measure)|
Genetic: RTVP-1 Gene
Cohort Level #1 1.0 x 1010vp Cohort Level #2 5.0x1010vp Cohort Level #3 1.0 x 1011vp Cohort Level #4 5.0x1011vp Cohort Level #5 1.0 x 1012vp Cohort Level #6 5.0x1012vp
One dose only followed by a radical prostatectomy 4 weeks later.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00403221
|United States, Texas|
|Baylor College of Medicine - Scott Department of Urology|
|Houston, Texas, United States, 77030|
|Principal Investigator:||Dov Kadmon, M.D.||Baylor College of Medicine|