Prostate Cancer
Conditions
Keywords
Vaccine, pTVG-HP, Prostate Cancer, Castrate Resistant
Brief summary
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.
Interventions
BIOLOGICALpTVG-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
Sponsors
National Cancer Institute (NCI)
University of Wisconsin, Madison
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With > = Grade 2 Autoimmune Events or >=Toxicities at Least Possibly Related to pTVG-HP With GM-CSF Study Treatment. | 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. | 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
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Who Experience at Least a Two-fold Increase in the PSA Doubling Time During the Treatment Period. | 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. | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled between 3/16/2009 and 4/24/2012 and were recruited from the UW Carbone Cancer Center Clinics
Participants by arm
| Arm | Count |
|---|---|
| 1: pTVG-HP With rhGM-CSF Every 3 Months Post Week 12 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.
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 | 8 |
| 2: pTVG-HP With rhGM-CSF Variable Dosing Post Week 12 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.
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. | 9 |
| Total | 17 |
Baseline characteristics
| Characteristic | 1: pTVG-HP With rhGM-CSF Every 3 Months Post Week 12 | 2: pTVG-HP With rhGM-CSF Variable Dosing Post Week 12 | Total |
|---|---|---|---|
| Age, Customized 40-49 years | 1 participants | 0 participants | 1 participants |
| Age, Customized 60-69 years | 1 participants | 6 participants | 7 participants |
| Age, Customized 70-79 years | 1 participants | 3 participants | 4 participants |
| Age, Customized 80-89 years | 5 participants | 0 participants | 5 participants |
| Race/Ethnicity, Customized White | 8 participants | 9 participants | 17 participants |
| Region of Enrollment United States | 8 participants | 9 participants | 17 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 9 / 9 |
| serious Total, serious adverse events | 3 / 8 | 1 / 9 |
Outcome results
Primary
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.
Time frame: Baseline and 1 year.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: pTVG-HP With rhGM-CSF Every 3 Months Post Week 12 | 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. | 3 participants |
| 2: pTVG-HP With rhGM-CSF Variable Dosing Post Week 12 | 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. | 6 participants |
Primary
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.
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: pTVG-HP With rhGM-CSF Every 3 Months Post Week 12 | Number of Participants With > = Grade 2 Autoimmune Events or >=Toxicities at Least Possibly Related to pTVG-HP With GM-CSF Study Treatment. | 1 participants |
| 2: pTVG-HP With rhGM-CSF Variable Dosing Post Week 12 | Number of Participants With > = Grade 2 Autoimmune Events or >=Toxicities at Least Possibly Related to pTVG-HP With GM-CSF Study Treatment. | 0 participants |
Secondary
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.
Time frame: one year from study entry
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: pTVG-HP With rhGM-CSF Every 3 Months Post Week 12 | The Number of Participants Who Are Metastasis-free at One Year. | 6 participants |
| 2: pTVG-HP With rhGM-CSF Variable Dosing Post Week 12 | The Number of Participants Who Are Metastasis-free at One Year. | 6 participants |
Secondary
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.
Time frame: Starting at Treatment Day 0 and continuing every 4-6 weeks until end of treatment period, an average of 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 1: pTVG-HP With rhGM-CSF Every 3 Months Post Week 12 | The Number of Participants Who Experience at Least a Two-fold Increase in the PSA Doubling Time During the Treatment Period. | 3 participants |
| 2: pTVG-HP With rhGM-CSF Variable Dosing Post Week 12 | The Number of Participants Who Experience at Least a Two-fold Increase in the PSA Doubling Time During the Treatment Period. | 4 participants |