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

NCT03541928 | Unknown Phase 2 DMC FDA Drug

• 1 other identifier: Pro00017515
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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

Keywords

gene therapy; untreated prostate cancer

Outcome Measures

Primary Outcomes (1)

• Biochemical control rate

  measured by PSA

  5-year biochemical disease free survival rate

Secondary Outcomes (3)

• Overall survival rate

  5-year overall survival rate

• Pathologic complete response rate

  After prostatectomy

• Safety based on questionnaire and clinical adverse event monitoring

  5-year post treatment

Study Arms (1)

Gene Therapy, ADT, RT, and Surgery

EXPERIMENTAL

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.

Drug: HSV-Tk; Drug: Valacyclovir; Drug: Bicalutamide; Drug: Leuprolide Acetate; Radiation: Brachytherapy, External beam radiotherapy; Procedure: Radical prostatectomy

Interventions

HSV-Tk DRUG

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.

Also known as: Gene therapy, AdV-tk gene therapy, Herpes simplex virus thymidine kinase

Gene Therapy, ADT, RT, and Surgery

Valacyclovir DRUG

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.

Also known as: Valtrex

Gene Therapy, ADT, RT, and Surgery

Bicalutamide DRUG

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.

Also known as: Casodex

Gene Therapy, ADT, RT, and Surgery

Leuprolide Acetate DRUG

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

Also known as: Lupron

Gene Therapy, ADT, RT, and Surgery

Brachytherapy, External beam radiotherapy RADIATION

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.

Also known as: HDR, EBRT

Gene Therapy, ADT, RT, and Surgery

Radical prostatectomy PROCEDURE

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.

Also known as: Prostatectomy

Gene Therapy, ADT, RT, and Surgery

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• The Methodist Hospital Research Institute: lead

Study Sites (1)

Houston Methodist Hospital

Houston, Texas, 77030, United States

RECRUITING

Related Publications (12)

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• Crook J, Ludgate C, Malone S, Perry G, Eapen L, Bowen J, Robertson S, Lockwood G. Final report of multicenter Canadian Phase III randomized trial of 3 versus 8 months of neoadjuvant androgen deprivation therapy before conventional-dose radiotherapy for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2009 Feb 1;73(2):327-33. doi: 10.1016/j.ijrobp.2008.04.075. Epub 2008 Aug 15.

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  PMID: 23157435 BACKGROUND

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Genetic Therapy; Valacyclovir; bicalutamide; Leuprolide; Brachytherapy; Prostatectomy

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics; Genetic Engineering; Genetic Techniques; Investigative Techniques; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Radiotherapy; Urologic Surgical Procedures, Male; Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• E. Brian Butler, MD

  The Methodist Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Emily Hsiao, Ph.D.

CONTACT

713-383-5115; khsiao@houstonmethodist.org

Christine O'Reilly

CONTACT

713-394-1107; coreilly@houstonmethodist.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of Radiation Oncology Department, Houston Methodist Hospital

Study Record Dates

• First Submitted: May 10, 2018
• First Posted: May 31, 2018
• Study Start: August 2, 2018
• Primary Completion: July 1, 2023
• Study Completion: July 1, 2023
• Last Updated: April 6, 2021

Record last verified: 2021-04

Locations

US (1)