Recruiting
Phase 2

HSV-tk+ Valacyclovir & ADT, Brachytherapy, EBRT, Prostatectomy

Sponsor:

The Methodist Hospital Research Institute

Code:

NCT03541928

Conditions

High-risk Prostate Cancer

Prostate Cancer

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Interventions

HSV-Tk

Valacyclovir

Bicalutamide

Leuprolide Acetate

Brachytherapy, External beam radiotherapy

Study Details

Brief 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

Study ID

NCT03541928

Start date

Aug 2, 2018

Status verified date

Apr, 2021

Completion date

Jul, 2023

Anticipated

Primary completion date

Jul, 2023

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: Male

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • All patients must have biopsy proven adenocarcinoma of the prostate
  • Patients in should have at least one or more of the following characteristics PSA>20, Gleason score 8-10, Primary Gleason pattern 5, >4 cores with Gleason 8-10, and Clinical stage T3a-T4.
  • No prior surgical, hormonal, or radiotherapy prostate treatment.
  • ECOG performance status 0-1
  • No evidence of metastatic disease or other malignancy (except squamous or basal cell skin cancers.
  • Patients must have PSA within 3 months of entry.
  • Signed informed consent to participate in the study must be obtained from patients after they have been fully informed of the nature and potential risks of the study by the investigator (or his/her designee) with the aid of written information.
  • Willing to provide biopsies as required by the study.
  • Patients must have adequate baseline organ function as assessed by the following laboratory values before initiating the protocol:
  • serum creatinine < 1.5 mg%
  • T. bilirubin < 2.5 mg%, ALT and AST < 2x normal
  • Pts > 100,000/mm3 , ANC> 1500 mm , Hgb> 10gm%
  • Normal partial thromboplastin time (PTT) and Pro-Thrombin Time (PT)

Exclusion Criteria:

  • Prior treatment with immunomodulatory therapy, immunotherapy, and/or gene vector therapy in the past 3 months.
  • Any cytotoxic chemotherapy, RT, or immunotherapy or any investigational drug within 3 weeks of study treatment start.
  • Evidence of metastatic disease
  • Prostate volume >50cc
  • Prior prostate surgery (hyperthermia, cryotherapy, etc.)
  • Prior pelvic radiotherapy
  • Prior androgen ablation hormonal therapy (except finasteride if discontinued > 3 mo. prior to enrollment)
  • Patients on corticosteroids or any immunosuppressive drugs.
  • History of liver disease, such as cirrhosis or active/chronic hepatitis B or C.
  • History of or current alcohol misuse/abuse within the past 12 months.
  • Known or suspected allergy or hypersensitivity to any component of the proposed regimen (gene vector/Valacyclovir).
  • Inability to swallow food or any condition of the upper gastrointestinal tract that precludes administration of oral medications (Valacyclovir).
  • No active malignancy except for non-melanoma skin cancer or in situ cervical cancer or treated cancer from which the patient has been continuously disease free for more than 5 years.
  • Presence of active or suspected acute or chronic uncontrolled infection or history of immunocompromise, including a positive HIV test result.
  • Patients < 18 years of age
  • Unwilling or unable to comply with the study protocol.

Study Design

Enrollment

60 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Gene Therapy, ADT, RT, and Surgery

The investigational gene therapy, ADV/HSV-tk, will be administered by injection into the prostate at 5 x 10\[11\] virus particles (1.25 x 10\[11\] virus particles per tumor quadrant in 4 quadrants) on day 0 and day 30.

The recommended dose of Valacyclovir for this trial is 2 g orally t.i.d. for 14 days (day 1 to day 15 and days 31 to 45).

The recommended dose for Bicalutamide therapy in combination with an LHRH analogue is one 50 mg tablet once daily (morning or evening).

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

Interventions

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.

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.

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.

Leuprolide Acetate

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

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.

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.

Primary outcome measure

  • Biochemical control rate [ Time Frame: 5-year biochemical disease free survival rate ]

Central Contacts and Locations

Central contacts

Emily Hsiao, Ph.D.

713-383-5115khsiao@houstonmethodist.org

Christine O'Reilly

713-394-1107coreilly@houstonmethodist.org

Locations

Houston Methodist Hospital

Recruiting

Houston, Texas, United States, 77030

More Information

Sponsor

The Methodist Hospital Research Institute

Last update posted

Apr 6, 2021

Last verified

Apr, 2021

Keywords

  • gene therapy
  • untreated prostate cancer

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by The Methodist Hospital Research Institute on 2021-04-06.