Clinical Trials /

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

NCT01913106

Description:

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.

Related Conditions:
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: Pro00000601
  • SECONDARY ID: IRB 0107-0009
  • NCT ID: NCT01913106

Conditions

  • Prostatic Neoplasms

Interventions

DrugSynonymsArms
HSV-tk +Valacyclovir in Combination with BrachytherapyIND 13567HSV-tk + Valacyclovir and Brachytherapy

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
HSV-tk + Valacyclovir and BrachytherapyExperimentalYou 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.
  • HSV-tk +Valacyclovir in Combination with Brachytherapy

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:N/A
Eligible Gender:Male
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

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

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:The Methodist Hospital System

Last Updated

June 29, 2016