Phase II High Risk Prostate Cancer Trial Using Gene & Androgen Deprivation Therapies, Radiotherapy, & Surgery

Summary

This is a prospective phase II study to assess the efficacy and toxicity of HSV-tk+ valacyclovir gene therapy in combination with androgen deprivation therapy, brachytherapy, external beam radiotherapy, and prostatectomy in previously untreated high-risk prostate cancer.

Conditions

• High-risk Prostate Cancer
• Prostate Cancer

Interventions

DRUG

HSV-Tk

Injection of the HSV-tk gene therapy product in four quadrants of prostate to enhance the immune system via "bystander effect" in which cytotoxicity is conferred to non-transduced neighboring cells. In vivo bystander effects are likely due to a combination of host immunological responses and to gap junction-mediated transport of phosphorylated prodrug metabolites to surrounding cells.

DRUG

Valacyclovir

The recommended dose for this trial is 2 g orally t.i.d. for 14 days (day 1 to day 15 and days 31 to 45). This dose has been calculated to give a similar AUC as 10 mg/kg of intravenous acyclovir administered every 8 hours. This is the same dose regimen used in a previous phase I clinical trial of ADV/HSV-tk plus acyclovir and topotecan in patients with recurrent ovarian cancer.

DRUG

Bicalutamide

The recommended dose for Bicalutamide therapy in combination with an LHRH analogue is one 50 mg tablet once daily (morning or evening), with or without food. It is recommended that Bicalutamide be taken at the same time each day. The use of an oral antiandrogen with medical castration for the treatment of prostate cancer is referred to as combined androgen blockade (CAB). Compared with LHRH-agonist monotherapy, CAB with bicalutamide did not reduce overall QoL but provided an early improvement in QoL related to lower urinary tract symptoms and pain.

DRUG

Leuprolide Acetate

Leuprolide acetate 7.5 mg depot injection will be injected monthly for a total of 2 months.

RADIATION

Brachytherapy, External beam radiotherapy

On day 60, patient will undergo high dose rate (HDR) Brachytherapy. The patient will have 8-14 needle catheters inserted under ultrasound guidance. CT simulation and radiation treatment planning will be performed. The needle catheters will be connected to an HDR afterloader containing an Iridium 192 source. A single dose of 1250cGy will be delivered.

PROCEDURE

Radical prostatectomy

approximately 2-3 weeks after radiotherapy completion, patient will undergo radical retropubic prostatectomy. Use of laparoscopy or robotic assistance will be at the urologist's discretion. Lymph node dissection will be performed.

Sponsors & Collaborators

• The Methodist Hospital Research Institute

  lead OTHER

Principal Investigators

• E. Brian Butler, MD · The Methodist Hospital Research Institute

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

MALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-08-02

Primary Completion

2023-07-31

Completion

2023-07-31

FDA Drug

Yes

Countries

• United States

Study Locations