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

  • STATUS
    Recruiting
  • End date
    Dec 21, 2028
  • participants needed
    25
  • sponsor
    The Methodist Hospital System
Updated on 21 January 2021
cancer
metastasis
brachytherapy
recurrent prostate cancer
external beam radiation therapy
cancer treatment

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.

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.

Details
Condition Malignant neoplasm of prostate, Prostate Cancer, Prostate Cancer, Early, Recurrent, Prostatic disorder, Prostate Disorders, Prostate Disorders, Prostate Cancer, Early, Recurrent, Prostate Cancer, prostate tumor, prostate tumors
Treatment HSV-tk +Valacyclovir in Combination with Brachytherapy
Clinical Study IdentifierNCT01913106
SponsorThe Methodist Hospital System
Last Modified on21 January 2021

Eligibility

Yes No Not Sure

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/l, platelets 100,000/l
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
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