Gene Therapy for Prostate Cancer That Returns After Radiation Therapy - Full Text View

Sponsors and Collaborators:	Mount Sinai School of Medicine U.S. Army Medical Research and Materiel Command
Information provided by:	Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:	NCT00110526

Purpose

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.

Condition	Intervention	Phase
Prostatic Neoplasms Neoplasm Recurrence, Local	Gene Transfer: Ad.hIL-12	Phase I

MedlinePlus related topics: Cancer Prostate Cancer

Drug Information available for: Interleukin-12

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title:	Phase I Trial of Adenovirus- Mediated IL-12 Gene Transduction in Patients With Radiorecurrent Prostate Cancer

Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:

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

Secondary Outcome Measures:

To assess serum levels of pro-inflammatory cytokines before and after vector injection
To assess T cell responses pre and post-IL-12 treatment against prostate antigens
To assess changes in PSA levels as a surrogate marker for prostate cancer following Ad.hIL-12 gene therapy

Estimated Enrollment:	24
Study Start Date:	April 2005
Estimated Study Completion Date:	April 2006

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.

Eligibility

Ages Eligible for Study:	40 Years to 75 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00110526

Locations

United States, New York
Mount Sinai School of Medicine	Recruiting
New York, New York, United States, 10029
Contact: Cynthia Knauer, RN, MS, AOCN 212-241-8121 cynthia.knauer@mountsinai.org
Contact: Simon Hall, M.D. (212)241-0045
Principal Investigator: Simon J Hall, MD

Sponsors and Collaborators

Mount Sinai School of Medicine

U.S. Army Medical Research and Materiel Command

More Information

Mount Sinai School of Medicine Department of Urology website This link exits the ClinicalTrials.gov site

Study ID Numbers:	GCO # 01-0595, A-11425
Study First Received:	May 10, 2005
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00110526
Health Authority:	United States: Food and Drug Administration

Keywords provided by Mount Sinai School of Medicine:

Prostate Cancer
Radiation Therapy
Local recurrence
Gene Therapy

Study placed in the following topic categories:

Interleukin-12
Prostatic Diseases
Genital Neoplasms, Male
Adenoviridae Infections
Urogenital Neoplasms

Neoplasm Recurrence, Local
Genital Diseases, Male
Prostatic Neoplasms
Recurrence

Additional relevant MeSH terms:

Disease Attributes
Neoplastic Processes
Neoplasms
Neoplasms by Site
Pathologic Processes

ClinicalTrials.gov processed this record on January 16, 2009