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

Phase I-II Study HSV-tk + Valacyclovir Therapy in Combination With Brachytherapy for Recurrent Prostate Cancer With or Without Metastatic Disease

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.

Study Overview

Status

Recruiting

Conditions

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 Type

Interventional

Enrollment (Anticipated)

25

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • Houston Methodist
        • Contact:
        • Contact:
        • Principal Investigator:
          • Edward B Butler, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

INCLUSION CRITERIA:

  • biopsy-proven local recurrence of prostate cancer without metastatic disease after the hormone therapy at least 2 year after the completion of definitive radiation therapy
  • Zubrod performance status 0-1
  • WBC ≥ 4,000/μl, platelets ≥ 100,000/μl
  • hemoglobin ≥ 8.5 mg/dl
  • normal partial thromboplastin time and prothrombin time
  • bilirubin < 1.5 mg/dl, and AST and alanine aminotransferase < 2.5 times the upper limit of normal
  • Serum creatinine ≤ 1.6 mg/dl
  • Must undergo pre-treatment evaluation of tumor extent and tumor measurement
  • Nutritional and general physical condition must be considered compatible with the proposed radio-therapeutic treatment
  • Not on any other experimental therapeutic cancer treatment
  • No active untreated infection
  • No major medical or psychiatric illness
  • International Prostate Symptom Score (IPSS) less than 15
  • Signed study-specific consent form prior to study entry
  • Prostate volume less than 50 cc
  • PSA > 10ng/ml within the past 3 months may enter study

EXCLUSION CRITERIA:

  • Symptomatic metastasis disease
  • Patients with a life expectancy < 10 years
  • Patients on corticosteroids or any immunosuppressive drugs.
  • HIV + patients
  • Patients with acute infections (viral, bacterial, or fungal infections requiring therapy)
  • Patients with cirrhosis.
  • Patients with collagen vascular diseases
  • International Prostate Symptom Score (IPSS) greater than 15
  • Prostate volume greater than 50 cc
  • Second active cancer except cutaneous cancer
  • Patients with history of allergies to valacyclovir, acyclovier or who cannot take oral pills

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
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 Names:
  • IND 13567

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
1. Safety based on standard laboratory and clinical adverse event monitoring
Time Frame: 5-year biochemical disease free survival rate
5-year biochemical disease free survival rate

Secondary Outcome Measures

Outcome Measure
Time Frame
Local control survival (measured by PSA and biopsy)
Time Frame: 5-year biochemical disease free survival rate
5-year biochemical disease free survival rate
Evaluate immunological markers
Time Frame: 5-year post treatment
5-year post treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Edward B Butler, MD, The Methodist Hospital Research Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2007

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

December 1, 2028

Study Registration Dates

First Submitted

July 25, 2013

First Submitted That Met QC Criteria

July 29, 2013

First Posted (Estimate)

July 31, 2013

Study Record Updates

Last Update Posted (Estimate)

July 1, 2016

Last Update Submitted That Met QC Criteria

June 29, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Other Study ID Numbers

  • Pro00000601
  • IRB 0107-0009 (Other Identifier: Houston Methodist Research Institute IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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