Gene Therapy for Prostate Cancer That Returns After Radiation Therapy

Prostatic Neoplasms Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00110526
• Other study ID #: GCO # 01-0595
• Secondary ID: A-11425
• Status: Withdrawn
• Phase: Phase 1
• First received: May 10, 2005
• Last updated: October 23, 2013
• Start date: April 2005
• Est. completion date: April 2008

Study information

• Verified date: October 2013
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: April 2008
• Est. primary completion date: April 2008
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 40 Years to 75 Years

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Neoplasm Recurrence, Local
• Neoplasms
• Prostatic Neoplasms
• Recurrence

Intervention

Genetic:
• Ad.hIL-12
Ad.hIL-12 intraprostatic injection IND

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Simon Hall	U.S. Army Medical Research and Materiel Command

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No

External Links

•   Mount Sinai School of Medicine Department of Urology website