HSV-tk + Valacyclovir Therapy in Combination With Brachytherapy for Recurrent Prostate Cancer

Phase 1

Recruiting

• Conditions: Prostatic Neoplasms
• Interventions: Drug: HSV-tk +Valacyclovir in Combination with Brachytherapy

• Registration Number: NCT01913106
• Lead Sponsor: The Methodist Hospital Research Institute

Brief Summary

The purpose of this study is to conduct a Phase I - II clinical trial to extend preclinical studies involving in situ HSV-tk + Valacyclovir gene therapy in combination with brachytherapy for recurrent prostate cancer. This will provide a novel therapeutic approach to prostate cancer and hopefully impact on the development of metastatic disease and the control of preexisting metastasis.

Detailed Description

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 Timeline

• Study Start: 2007-06
• Study First Submitted: 2013-07-25
• Study First Submitted QC: 2013-07-29
• Study First Posted: 2013-07-31
• Status Verified: 2016-06
• Last Update Submitted: 2016-06-29
• Last Update Posted: 2016-07-01
• Primary Completion: 2018-12
• Study Completion: 2028-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Male
• Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HSV-tk + Valacyclovir and Brachytherapy	HSV-tk +Valacyclovir in Combination with 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.

Primary Outcome Measures

Name	Time	Method
1. Safety based on standard laboratory and clinical adverse event monitoring	5-year biochemical disease free survival rate

Secondary Outcome Measures

Name	Time	Method
Evaluate immunological markers	5-year post treatment
Local control survival (measured by PSA and biopsy)	5-year biochemical disease free survival rate

Trial Locations

Locations (1)

Houston Methodist; 🇺🇸 Houston, Texas, United States