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

Study Overview
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Brief Summary
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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.

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

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: pTVG-HP with rhGM-CSF
* Biological: pTVG-HP with rhGM-CSF


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>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. | Biological: pTVG-HP with rhGM-CSF<br>* 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<br>* Other names: DNA-based vaccine encoding PAP;|
| Experimental: 2<br>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. | Biological: pTVG-HP with rhGM-CSF<br>* 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.<br>* Other names: DNA-based vaccine encoding PAP;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With > = Grade 2 Autoimmune Events or >=Toxicities at Least Possibly Related to pTVG-HP With GM-CSF Study Treatment. | 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. | 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 | 
| 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. | 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. | Baseline and 1 year. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants Who Experience at Least a Two-fold Increase in the PSA Doubling Time During the Treatment Period. | 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. | Starting at Treatment Day 0 and continuing every 4-6 weeks until end of treatment period, an average of 2 years | 
| The Number of Participants Who Are Metastasis-free at One Year. | 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. | one year from study entry | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, pTVG-HP, Prostate Cancer, Castrate Resistant