Gene Therapy for Prostate Cancer That Returns After Radiation Therapy

This study has been withdrawn prior to enrollment.
(No participants met eligibility requirements)
Sponsor:
Collaborator:
U.S. Army Medical Research and Materiel Command
Information provided by (Responsible Party):
Simon Hall, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT00110526
First received: May 10, 2005
Last updated: October 23, 2013
Last verified: October 2013
  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
Genetic: Ad.hIL-12
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Trial of Adenovirus- Mediated IL-12 Gene Transduction in Patients With Radiorecurrent Prostate Cancer

Resource links provided by NLM:


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

Primary Outcome Measures:
  • maximum cytokine gene therapy level [ Time Frame: after 56 weeks, every 6 months up to 15 years ] [ Designated as safety issue: Yes ]
    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:
  • serum pro-inflammatory cytokines levels [ Time Frame: up to 15 years ] [ Designated as safety issue: Yes ]
    To assess serum levels of pro-inflammatory cytokines before and after vector injection and will continue every 3 days until normalized

  • To assess T cell responses pre and post-IL-12 treatment against prostate antigens [ Time Frame: Day 7 post vector injection ] [ Designated as safety issue: Yes ]
    Day 7,14,21 and 28 post vector injection

  • To assess T cell responses pre and post-IL-12 treatment against prostate antigens [ Time Frame: Day 14 post vector injection ] [ Designated as safety issue: Yes ]
    Day 7,14,21 and 28 post vector injection

  • To assess T cell responses pre and post-IL-12 treatment against prostate antigens [ Time Frame: Day 21 post vector injection ] [ Designated as safety issue: Yes ]
    Day 7,14,21 and 28 post vector injection

  • To assess T cell responses pre and post-IL-12 treatment against prostate antigens [ Time Frame: Day 28 post vector injection ] [ Designated as safety issue: Yes ]
    Day 7,14,21 and 28 post vector injection

  • To assess changes in PSA levels as a surrogate marker for prostate cancer following Ad.hIL-12 gene therapy [ Time Frame: 1 week after vector injection ] [ Designated as safety issue: No ]
    1,2,4,6 and 8 weeks after vector injection

  • To assess changes in PSA levels as a surrogate marker for prostate cancer following Ad.hIL-12 gene therapy [ Time Frame: 2 weeks after vector injection ] [ Designated as safety issue: No ]
    1,2,4,6 and 8 weeks after vector injection

  • To assess changes in PSA levels as a surrogate marker for prostate cancer following Ad.hIL-12 gene therapy [ Time Frame: 4 weeks after vector injection ] [ Designated as safety issue: No ]
    1,2,4,6 and 8 weeks after vector injection

  • To assess changes in PSA levels as a surrogate marker for prostate cancer following Ad.hIL-12 gene therapy [ Time Frame: 6 weeks after vector injection ] [ Designated as safety issue: No ]
    1,2,4,6 and 8 weeks after vector injection

  • To assess changes in PSA levels as a surrogate marker for prostate cancer following Ad.hIL-12 gene therapy [ Time Frame: 8 weeks after vector injection ] [ Designated as safety issue: No ]
    1,2,4,6 and 8 weeks after vector injection


Enrollment: 0
Study Start Date: April 2005
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ad.hIL-12 Genetic: Ad.hIL-12
Ad.hIL-12 intraprostatic injection IND

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Sponsors and Collaborators
Simon Hall
U.S. Army Medical Research and Materiel Command
Investigators
Principal Investigator: Simon Hall, MD Mount Sinai School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Simon Hall, MD, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT00110526     History of Changes
Other Study ID Numbers: GCO # 01-0595, A-11425
Study First Received: May 10, 2005
Last Updated: October 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Mount Sinai School of Medicine:
Prostate Cancer
Radiation Therapy
Local recurrence
Gene Therapy

Additional relevant MeSH terms:
Neoplasms
Neoplasm Recurrence, Local
Prostatic Neoplasms
Recurrence
Neoplastic Processes
Pathologic Processes
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Genital Diseases, Male
Prostatic Diseases
Disease Attributes

ClinicalTrials.gov processed this record on August 26, 2014