Clinical trial NCT01913106: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prostatic Neoplasms
Lead sponsor: The Methodist Hospital Research Institute
Sponsor class: OTHER
First posted: 2013-07-31
Enrollment: 25
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 1. Safety based on standard laboratory and clinical adverse event monitoring
timeFrame: 5-year biochemical disease free survival rate
Secondary outcomes:
measure: Local control survival (measured by PSA and biopsy)
timeFrame: 5-year biochemical disease free survival rate
measure: Evaluate immunological markers
timeFrame: 5-year post treatment
Other outcomes:
Locations:
city: Houston
country: United States
facility: Houston Methodist
state: Texas
Study officials:
affiliation: The Methodist Hospital Research Institute
name: Edward B Butler, MD
role: PRINCIPAL_INVESTIGATOR
References: