HSV-tk + Valacyclovir Therapy in Combination With Brachytherapy for Recurrent Prostate Cancer
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|ClinicalTrials.gov Identifier: NCT01913106|
Recruitment Status : Recruiting
First Posted : July 31, 2013
Last Update Posted : July 1, 2016
|Condition or disease||Intervention/treatment||Phase|
|Prostatic Neoplasms||Drug: HSV-tk +Valacyclovir in Combination with Brachytherapy||Phase 1 Phase 2|
This investigational new drug application describes a proposed phase I/II study designed to assess the safety and efficacy of AdV-tk gene therapy in combination with standard brachytherapy for patients with locally recurrent prostate cancer after having failed radiation as a primary treatment with or without minimal metastasis. These patients do not have any standard treatment that has been demonstrated to have a high degree of efficacy in eradicating the tumor with a reasonable degree of safety. Thus, the potential risks associated with the use of gene therapy in this group would appear reasonable. This application is for use of a replication defective adenovirus vector (ADV/RSV-tk) delivering the HSV-tk gene as a biologic vector for gene therapy.
Direct introduction of therapeutic genes into malignant cells in vivo may provide an effective treatment of solid tumors such as prostate cancer. The herpes simplex virus thymidine kinase (HSV-tk) gene codes for an enzyme which phosphorylates the nucleoside analog ganciclovir (GCV) into an intermediate that is incorporated into newly synthesized DNA and terminates further replication, leading to cell death. Since normal mammalian cells do not possess this enzyme, cytotoxicity depends on the successful introduction and expression of the HSV-tk gene, phosphorylation of ganciclovir and synthesis of DNA. Non-dividing cells may express HSV-tk and phosphorylate ganciclovir but are not harmed since they do not synthesize DNA. This approach is especially suitable for the treatment of tumors where rapidly dividing tumor cells are adjacent to tissues made up largely of non-proliferating cells. Using human and animal models for prostate cancer we have demonstrated that adenovirus-mediated transfer of the HSV-tk gene resulted in sensitivity to ganciclovir in vitro and growth suppression of mouse prostate cancer in vivo.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I-II Study HSV-tk + Valacyclovir Therapy in Combination With Brachytherapy for Recurrent Prostate Cancer With or Without Metastatic Disease|
|Study Start Date :||June 2007|
|Estimated Primary Completion Date :||December 2018|
|Estimated Study Completion Date :||December 2028|
Experimental: HSV-tk + Valacyclovir and Brachytherapy
You will be given an antibiotic (Ciproflaxin) to take twice a day beginning the day before the procedure, and continuing for a total of 3 - 5 days. You will also be given 4 pills called (Valtrex) valacyclovir to take three times a day for 14 days, beginning the day before the procedure. You will be given a pill diary in which you will record each dose of valacyclovir that you take. You will receive brachytherapy (radioactive seed placement) the day after you begin taking your pills. After the radioactive seeds are placed, while you are still in the operating room, you will receive an injection into your prostate of 1 or 2 ml (one-fifth or two-fifths of a teaspoon) of a solution of the vector carrying the gene.
Drug: HSV-tk +Valacyclovir in Combination with Brachytherapy
The investigators insert a gene from a herpes simplex virus (HSV), which is a small piece of the basic structure of the virus, into the prostate gland tumor cells. The gene is called the thymidine kinase (tk) gene, which the cell uses to make a protein that can change valacyclovir, The way the tk gene will be transported into the tumor cells is by using a vector or "vehicle" to carry the tk gene into the cells. In this case the vector is a virus - an adenovirus. Scientists at the Department of Cell and Gene Therapy at The Methodist Hospital removed a portion of the adenovirus' genetic material that allows it to replicate so that it cannot cause infections. In place of the removed genetic material the scientists inserted the tk gene. Now the vector can carry the tk gene into tumor cells. When the vector/gene combination gets into tumor cells, it inserts itself into the cells' command center (nucleus) and tells the tumor cells to begin making thymidine kinase protein.
Other Name: IND 13567
- 1. Safety based on standard laboratory and clinical adverse event monitoring [ Time Frame: 5-year biochemical disease free survival rate ]
- Local control survival (measured by PSA and biopsy) [ Time Frame: 5-year biochemical disease free survival rate ]
- Evaluate immunological markers [ Time Frame: 5-year post treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01913106
|Contact: Brent Bell, PA-Cemail@example.com|
|Contact: Brian Butler, MDfirstname.lastname@example.org|
|Principal Investigator:||Edward B Butler, MD||Houston Methodist|