Two-Arm Study of a DNA Vaccine Encoding Prostatic Acid Phosphatase (PAP) in Patients With Non-Metastatic Castrate-Resistant Prostate Cancer

Overview

The investigators are trying to find new methods to treat prostate cancer. The approach is to try to enhance patients' own immune response against the cancer. In this study, the investigators will be testing the safety of a vaccine that may be able to help the body fight prostate cancer.

The vaccine, called pTVG-HP, is a piece of DNA genetic material that contains genetic code for a protein that is made by the prostate gland, called prostatic acid phosphatase (PAP). The vaccine will be given together with a substance called an adjuvant. Adjuvants are typically given with vaccines and can improve the effect of the vaccine. The adjuvant that will be used in this study is called granulocyte-macrophage colony-stimulating factor (GM-CSF).

The main purpose of this study is to find out whether the vaccine generates long-lived immune responses, and whether a better schedule of vaccination can be found by doing frequent laboratory testing for immune responses. The investigators also want to see if the vaccine stimulates any immune reaction against cancer cells.

Full Title of Study: “A Pilot Randomized Two-Arm Study of a DNA Vaccine Encoding Prostatic Acid Phosphatase (PAP) in Patients With Non-Metastatic Castrate-Resistant Prostate Cancer”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: February 17, 2014

Interventions

  • Biological: pTVG-HP with rhGM-CSF
    • pTVG-HP (100 µg) with rhGM-CSF (200 µg) administered i.d. biweekly for 6 total doses, followed by pTVG-HP (100 µg) with rhGM-CSF (200 µg) administered i.d. every 3 months until radiographic disease progression
  • Biological: pTVG-HP with rhGM-CSF
    • pTVG-HP (100 µg) with rhGM-CSF (200 µg) administered i.d. biweekly for a minimum of 6 total doses, and continuing biweekly until evidence of T-cell immune response, and then following a booster schedule as defined by evidence of T-cell immune response.

Arms, Groups and Cohorts

  • Experimental: 1
    • Intradermal vaccinations of a DNA vaccine encoding PAP, with GM-CSF as an adjuvant given every 2 weeks for the first 12 weeks, then every 12 weeks until disease progression.
  • Experimental: 2
    • Intradermal vaccinations of a DNA vaccine encoding PAP, with GM-CSF as an adjuvant given every 2 weeks for the first 12 weeks, then given every 2-week, 4-week, or 3-month intervals as dictated by cellular immune response measurement.

Clinical Trial Outcome Measures

Primary Measures

  • Number of Participants With > = Grade 2 Autoimmune Events or >=Toxicities at Least Possibly Related to pTVG-HP With GM-CSF Study Treatment.
    • Time Frame: From the time the patient begins treatment until 30 days after the last treatment with pTVG-HP vaccine, up to a maximum of 2 years
    • The number and severity of toxicity incidents occurring between the pre-treatment and the final off-study evaluation will be collected and assigned an attribution. The toxicities observed will be summarized in terms of types and severities by the NCI Common Terminology Criteria version 3 for each study arm. The number of subjects experiencing grade 2 or higher autoimmune events or grade 3 or higher toxicities felt to be at least possibly related to pTVG-HP with GM-CSF study treatment will be compared between the two arms.
  • Number of Participants Who Experience at Least a 3-fold Higher PAP-specific T-cell Frequency or Proliferation Index at One Year Compared to Baseline.
    • Time Frame: Baseline and 1 year.
    • The number of patients with a T-cell immune response will be determined for each study arm. An immune response will be defined as a PAP-specific T-cell frequency or proliferation index at 1 year that is at least 3-fold higher than the baseline T-cell frequency or proliferation index.

Secondary Measures

  • The Number of Participants Who Experience at Least a Two-fold Increase in the PSA Doubling Time During the Treatment Period.
    • Time Frame: Starting at Treatment Day 0 and continuing every 4-6 weeks until end of treatment period, an average of 2 years
    • The number of subjects who experience at least a two-fold increase in the PSA doubling time will be documented for each study arm. The PSA doubling time will be calculated using all PSA values obtained starting on Treatment Day 0 and continuing to end of treatment period and compared to the PSA doubling time collected at study entry prior to beginning study treatment.
  • The Number of Participants Who Are Metastasis-free at One Year.
    • Time Frame: one year from study entry
    • The number of subjects who are metastatic-free at one year after starting study treatment will be tabulated for each arm. CT Scans and Bone Scans will be obtained at one year to determine whether metastatic disease is present.

Participating in This Clinical Trial

Inclusion Criteria

  • Diagnosis of Prostate Cancer
  • Castrate Resistant Disease with rising PSA despite continuous treatment with orchiectomy or a LHRH agonist
  • Rising PSA after treatment and withdrawal of anti-androgen
  • Serum Testosterone <50ng/mL
  • Normal organ function per laboratory tests

Exclusion Criteria

  • No evidence of immunosuppression or on treatment with immunosuppressive agents
  • Cannot have discontinued LHRH agonist treatment (if not previously treated by orchiectomy) within 6 months prior to study entry
  • Must not be concurrently taking other medications or supplements with known hormonal effects (other than the LHRH agonist noted above).
  • Cannot have any evidence for metastatic disease on bone or CT scan
  • Unable or unwilling to undergo two leukapheresis procedure

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University of Wisconsin, Madison
  • Collaborator
    • National Cancer Institute (NCI)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Douglas McNeel, MD, Principal Investigator, University of Wisconsin, Madison

Clinical trials entries are delivered from the US National Institutes of Health and are not reviewed separately by this site. Please see the identifier information above for retrieving further details from the government database.

At TrialBulletin.com, we keep tabs on over 200,000 clinical trials in the US and abroad, using medical data supplied directly by the US National Institutes of Health. Please see the About and Contact page for details.