Gene Therapy for Prostate Cancer That Returns After Radiation Therapy

Phase I Trial of Adenovirus- Mediated IL-12 Gene Transduction in Patients With Radiorecurrent Prostate Cancer

The purpose of this research study is to test a new treatment for prostate cancer. We have been exploring the use of cytokine (immune stimulating) gene therapy by directly injecting a virus which produces a cytokine called interleukin-12 (IL-12) into the prostate gland to control tumor growth. We propose to explore the use of adenovirus-mediated human interleukin-12 (Ad.hIL-12) in patients with recurrent non-metastatic prostate cancer following radiation therapy in a Phase I trial. Participants will be placed in rising dose groups with the primary endpoint of learning the maximum dose that can safely be given by injection directly into the prostate gland. Toxicity will be determined through physical examination, laboratory values, and blood levels of cytokines. Evidence of an immune response against prostate proteins will also be monitored. If the treatment works, the cancer will shrink or not grow. This will be monitored by prostate specific antigen (PSA) levels in the blood. However, we do not know if this treatment will be effective. If the PSA continues to rise after treatment, participants will be taken off study and offered other treatment. There is no compensation for participation in this research study. There will be no charge for the treatment with gene therapy or the monitoring associated with this research study. Monitoring will occur in a specially designated clinical research center.

Study Overview

• Status: Withdrawn
• Conditions: Prostatic Neoplasms; Neoplasm Recurrence, Local
• Intervention / Treatment: Genetic: Ad.hIL-12

Detailed Description

Patients with radiorecurrent prostate cancer have few viable treatment options, both in terms of efficacy and morbidity. Local therapies fail even in highly selected patients due to locally advanced disease, microscopic metastases, and a worsening of the biology of cancer cells. Furthermore, attempts at salvage local treatments have the complications of incontinence, impotence and in some cases unremitting penile pain. Pre-clinical studies in a mouse model of prostate cancer have noted the potential benefit of adenovirus-mediated gene therapy to deliver IL-12 in this clinical scenario. This treatment was able to significantly growth suppress the injected tumor to prolong survival and reduce the number of pre-established metastases. The mechanisms underlying this activity involved both innate immunity (neutrophils and natural killer [NK] cells) and acquired immunity ( T cells) and enhanced expression of Fas to further sensitize Fas/Fas ligand (FasL) killing.

This is a Phase I study. Therefore, the primary objective is finding the Maximum Tolerated Dose. Within this realm will be monitoring of pro-inflammatory cytokines. Secondary aspects will involve correlating important mechanisms identified in the pre-clinical model: induction of T cells.

• Study Type: Interventional
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• A local recurrence of prostate cancer (in or next to gland) following treatment by radiation therapy (either external beam or seed implantation)
• Rising PSA (Prostate Specific Antigen) on at least three occasions separated by two weeks
• Ultrasound guided biopsy to diagnose recurrent disease within the prostate
• No evidence of prostate cancer that has spread on bone scan or Computed Tomography (CT) scan
• No hormone therapy at time of enrollment to the research study

Exclusion Criteria:

• Radical prostatectomy for treatment of prostate cancer
• Detectable spread of prostate cancer on bone or CT scan
• Immunosuppressive medication within two months of the study
• Acute infection (any bacterial, viral, fungal infection requiring specific therapy)
• HIV disease
• Other significant medical or psychiatric conditions which pose high risk for an investigational study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ad.hIL-12	Genetic: Ad.hIL-12; Ad.hIL-12 intraprostatic injection IND

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
maximum cytokine gene therapy level	To study in a Phase I clinical trial the safety of intraprostatic injection of a replication incompetent adenovirus expressing hIL-12 in patients with radiorecurrent prostate cancer	after 56 weeks, every 6 months up to 15 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum pro-inflammatory cytokines levels	To assess serum levels of pro-inflammatory cytokines before and after vector injection and will continue every 3 days until normalized	up to 15 years
To assess T cell responses pre and post-IL-12 treatment against prostate antigens	Day 7,14,21 and 28 post vector injection	Day 7 post vector injection
To assess T cell responses pre and post-IL-12 treatment against prostate antigens	Day 7,14,21 and 28 post vector injection	Day 14 post vector injection
To assess T cell responses pre and post-IL-12 treatment against prostate antigens	Day 7,14,21 and 28 post vector injection	Day 21 post vector injection
To assess T cell responses pre and post-IL-12 treatment against prostate antigens	Day 7,14,21 and 28 post vector injection	Day 28 post vector injection
To assess changes in PSA levels as a surrogate marker for prostate cancer following Ad.hIL-12 gene therapy	1,2,4,6 and 8 weeks after vector injection	1 week after vector injection
To assess changes in PSA levels as a surrogate marker for prostate cancer following Ad.hIL-12 gene therapy	1,2,4,6 and 8 weeks after vector injection	2 weeks after vector injection
To assess changes in PSA levels as a surrogate marker for prostate cancer following Ad.hIL-12 gene therapy	1,2,4,6 and 8 weeks after vector injection	4 weeks after vector injection
To assess changes in PSA levels as a surrogate marker for prostate cancer following Ad.hIL-12 gene therapy	1,2,4,6 and 8 weeks after vector injection	6 weeks after vector injection
To assess changes in PSA levels as a surrogate marker for prostate cancer following Ad.hIL-12 gene therapy	1,2,4,6 and 8 weeks after vector injection	8 weeks after vector injection

Collaborators and Investigators

• Sponsor: Simon Hall
• Collaborators: U.S. Army Medical Research and Development Command
• Investigators: Principal Investigator: Simon Hall, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

Helpful Links

• Mount Sinai School of Medicine Department of Urology website

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: May 10, 2005
• First Submitted That Met QC Criteria: May 10, 2005
• First Posted (Estimate): May 11, 2005

Study Record Updates

• Last Update Posted (Estimate): October 24, 2013
• Last Update Submitted That Met QC Criteria: October 23, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: Gene Therapy; Prostate Cancer; Radiation Therapy; Local recurrence
• Additional Relevant MeSH Terms: Pathologic Processes; Urogenital Neoplasms; Neoplasms by Site; Disease Attributes; Genital Neoplasms, Male; Prostatic Diseases; Neoplastic Processes; Neoplasms; Prostatic Neoplasms; Recurrence; Neoplasm Recurrence, Local
• Other Study ID Numbers: GCO # 01-0595; A-11425