Dose Finding Study of a DNA Vaccine Delivered With Intradermal Electroporation in Patients With Prostate Cancer

Study Overview
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Brief Summary
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This study will assess the feasibility and safety of vaccination with increasing doses of xenogenic DNA administered intradermally in combination with electroporation in patients with relapse of prostate cancer. The DNA encodes prostate specific antigen (PSA) from Rhesus Macaque (Macaca mulatta), a protein that is 89% homologous to human PSA. The study will also assess the safety and functionality of the DERMA VAX™ (Cyto Pulse Sciences) DNA vaccine delivery system.

Official Title
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DNA Vaccine Coding for the Rhesus Prostate Specific Antigen (rhPSA) and Electroporation in Patients With Relapsed Prostate Cancer. A Phase I/II Study

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: pVAXrcPSAv53l (DNA encoding rhesus PSA)
* Device: DERMA VAX™ intradermal DNA delivery system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male patients. Age >18 years. HLA-A*0201 positive. Histologically confirmed prostate cancer. Minimum two (2) and maximum four (4) years after treatment with curative or salvage radiotherapy. Serum testosterone within normal range. Increasing PSA from a previous reference value on two (2) consecutive occasions at least one month apart and with a minimum of 2 ng/mL above nadir. PSA doubling time is one (1) year or less. No evidence of metastatic prostate cancer. Karnofsky performance status ≥ 80. Adequate organ function: AST and ALT ≤ 2.0 x upper limit of normal (ULN); total serum bilirubin ≤ 1.5 x ULN Calcium ≤ 2.6 mmol/L, serum creatinine ≤ 1.5 x ULN Hb ≥ 100 g/L; absolute leukocyte count ≥ 3.0 x 109 /L; platelets ≥100 x 109 /L Life expectancy ≥ 12 months. Swedish or English speaking subjects only. Written informed consent (subjects must be capable of providing their own informed consent). Exclusion Criteria: Previous ablation of testis. Radiologic evidence of metastatic disease. Prior chemotherapy or investigational therapy/agents within 4 weeks. Active bacterial, viral or fungal infection. Carrier of HIV, HBV, or HCV. Immunosuppressed (post splenectomy, post stem cell transplantation) or on immunosuppressive therapy other than inhaled or replacement corticosteroids. Any other major illness or peripheral blood vein status that, in the investigator's judgement, will substantially increase the risk associated with sampling or participation in this study. Subjects with cardiac demand pacemakers. Any reason why, in the opinion of the investigator, the patient should not participate.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort I<br>50 µg DNA/dose, 3 patients | Biological: pVAXrcPSAv53l (DNA encoding rhesus PSA)<br>* 5 doses, 4 weeks apart<br>* Other names: rhPSA;Device: DERMA VAX™ intradermal DNA delivery system<br>* in vivo electroporation is applied after each DNA injection<br>* Other names: Derma Vax;|
| Experimental: Cohort II<br>150 µg DNA/dose, 3 patients | Biological: pVAXrcPSAv53l (DNA encoding rhesus PSA)<br>* 5 doses, 4 weeks apart<br>* Other names: rhPSA;Device: DERMA VAX™ intradermal DNA delivery system<br>* in vivo electroporation is applied after each DNA injection<br>* Other names: Derma Vax;|
| Experimental: Cohort III<br>400 µg DNA/dose, 3 patients | Biological: pVAXrcPSAv53l (DNA encoding rhesus PSA)<br>* 5 doses, 4 weeks apart<br>* Other names: rhPSA;Device: DERMA VAX™ intradermal DNA delivery system<br>* in vivo electroporation is applied after each DNA injection<br>* Other names: Derma Vax;|
| Experimental: Cohort IV<br>1000 µg DNA/dose, 3 patients | Biological: pVAXrcPSAv53l (DNA encoding rhesus PSA)<br>* 5 doses, 4 weeks apart<br>* Other names: rhPSA;Device: DERMA VAX™ intradermal DNA delivery system<br>* in vivo electroporation is applied after each DNA injection<br>* Other names: Derma Vax;|
| Experimental: Cohort V<br>Optimal dose to be determined, 6 patients | Biological: pVAXrcPSAv53l (DNA encoding rhesus PSA)<br>* 5 doses, 4 weeks apart<br>* Other names: rhPSA;Device: DERMA VAX™ intradermal DNA delivery system<br>* in vivo electroporation is applied after each DNA injection<br>* Other names: Derma Vax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the feasibility and safety of escalating doses of pVAXrcPSAv53l DNA vaccine, administered intradermally in combination with electroporation in patients with relapse of prostate cancer. |  | From start of treatment to 30 days (safety) or up to 12 months (immunological & clinical) post last vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess the safety and functionality of the DERMA VAX™ in vivo electroporation DNA vaccine delivery system. |  | From start of treatment to 30 days (safety) or up to 12 months (immunological & clinical) post last vaccination | 
| Evaluate the PSA-specific immune response induced by the vaccine. |  | From start of treatment to 30 days (safety) or up to 12 months (immunological & clinical) post last vaccination | 
| Identify an anti-tumor effect of the vaccine. |  | From start of treatment to 30 days (safety) or up to 12 months (immunological & clinical) post last vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DNA, Vaccine, Electroporation, xenogenic, PSA