Prostate Cancer
Conditions
Keywords
Vaccine, pTVG-HP, Prostate Cancer, Castrate Resistant
Brief summary
This randomized pilot clinical trial studies sipuleucel-T with or without deoxyribonucleic acid (DNA) vaccine therapy in treating patients with prostate cancer that has not responded to previous treatment with hormones and has spread to other places in the body. Vaccines may help the body build an effective immune response to kill tumor cells. It is not yet known whether giving sipuleucel-T vaccine works better with or without DNA vaccine therapy in treating prostate cancer.
Interventions
BIOLOGICALsipuleucel-T
Given IV
BIOLOGICALDNA Vaccine
Given ID
Sponsors
Dendreon
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
* Histologically confirmed diagnosis of prostate cancer (adenocarcinoma of the prostate) * Metastatic disease as evidenced by the presence of soft tissue and/or bone metastases on imaging studies (computed tomography \[CT\] of abdomen/pelvis, bone scintigraphy) * Castrate-resistant disease, defined as follows: * All patients must have received standard of care androgen deprivation treatment before trial entry (surgical castration versus gonadotropin-releasing hormone \[GnRH\] analogue or antagonist treatment), and subjects receiving GnRH analogue or antagonist must continue this treatment throughout the time on this study * Patients may have been treated previously with a nonsteroidal antiandrogen, with evidence of disease progression subsequently; subjects must be off use of anti-androgen for at least 4 weeks (for flutamide) or 6 weeks (for bicalutamide or nilutamide) prior to registration \*\* Subjects who demonstrate an anti-androgen withdrawal response, defined as a \>= 25% decline in PSA within 4-6 week of stopping a nonsteroidal antiandrogen are not eligible until the PSA rises above the nadir observed after antiandrogen withdrawal * Castration levels of testosterone (\< 50 ng/dL) within 2 weeks of registration * Progressive disease while receiving androgen deprivation therapy defined by any one of the following as per the Prostate Cancer Clinical Trials Working Group 2 (PCWG2) bone scan criteria or Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 during or after completing last therapy: * PSA: at least two consecutive rises in serum PSA, obtained at a minimum of 1-week intervals, and each value \>= 2.0 ng/mL * Measurable disease: \>= 50% increase in the sum of the cross products of all measurable lesions or the development of new measurable lesions; the short axis of a target lymph node must be at least 15 mm by spiral CT to be considered a target lesion * Non-measurable (bone) disease: the appearance of two or more new areas of uptake on bone scan consistent with metastatic disease compared to previous imaging during castration therapy; the increased uptake of pre-existing lesions on bone scan will not be taken to constitute progression, and ambiguous results must be confirmed by other imaging modalities (e.g. X-ray, CT or magnetic resonance imaging \[MRI\]) * Must have \>= 3 serum PSA values obtained over at least a 12 week period of time prior to registration, including the day of screening, to calculate a PSA doubling time; Note: PSA's are not required to be obtained at the same laboratory; use all PSA values that have been done in last 6 months to calculate PSA doubling time * Life expectancy of at least 6 months * Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 * White blood cell \>= 2000/mm\^3 * Absolute neutrophil count \>= 1000/mm\^3 * Hemoglobin (HgB) \>= 9.0 mg/dL * Platelets \>= 100,000/mm\^3 * Creatinine =\< 2.0 mg/dL * Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =\< 2.5 x institutional upper limit of normal * Negative serology tests for human immunodeficiency virus (HIV) 1 and 2, and for active hepatitis B or hepatitis C, within 14 days of first peripheral blood collection for sipuleucel-T * Patients must be at least 4 weeks from any prior treatments and have recovered (to \< grade 2) from acute toxicity attributed to this prior treatment * Patients must be informed of the experimental nature of the study and its potential risks, and must sign an Institutional Review Board (IRB)-approved written informed consent form indicating such an understanding
Exclusion criteria
* Small cell or other variant prostate cancer histology * Patients may not be receiving other investigational agents or be receiving concurrent anticancer therapy other than androgen deprivation * Symptomatic metastatic disease, as defined by the need for opioid analgesics for the treatment of pain attributed to a prostate cancer metastatic lesion; patients receiving opioids must receive approval from the principal investigator (PI) for eligibility * Patients may not have been treated with prior sipuleucel-T * Treatment with any of the following medications within 28 days of registration, or while on study, is prohibited: * Systemic corticosteroids (at doses over the equivalent of 1 mg prednisone daily); inhaled, intranasal or topical corticosteroids are acceptable * Prostate cancer (PC)-SPES * Saw palmetto * Megestrol * Ketoconazole * 5-alpha-reductase inhibitors-patients already taking 5-alpha-reductase inhibitors prior to 28 days prior to registration may stay on these agents throughout the course of therapy, but these should not be started while patients are on study * Diethyl stilbestrol * Abiraterone * Any other hormonal agent or supplement being used with the intent of cancer treatment * External beam radiation therapy within 4 weeks of registration is prohibited, or anticipated need for radiation therapy (e.g. imminent pathological fracture or spinal cord compression) within 3 months of registration * Major surgery within 4 weeks of registration is prohibited * Prior cytotoxic chemotherapy (e.g. docetaxel, mitoxantrone, cabazitaxel) within 6 months of registration is prohibited * Patients with a history of life-threatening autoimmune disease * Patients who have undergone splenectomy * Patients must not have other active malignancies other than non-melanoma skin cancers or carcinoma in situ of the bladder; subjects with a history of other cancers who have been adequately treated and have been recurrence-free for \>= 3 years are eligible * Patients with known brain metastases * Any antibiotic therapy or evidence of infection within 1 week of registration * Any other medical intervention or condition, which, in the opinion of the PI could compromise patient safety or adherence with the study requirements * Patients cannot have concurrent enrollment on other phase I, II, or III investigational treatment studies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Immune Response Following Treatment | 12 months | The primary immunological goal of this study was to determine whether booster immunizations with a DNA vaccine encoding PAP could augment the number of PAP-specific effector and memory T cells following treatment with sipuleucel-T, or prolong the duration of detectable T-cell response. All subjects received a tetanus booster immunization prior to beginning the immunization series, providing a separate test of an individual's immune responsiveness. Responses to PSA, a non-target prostate specific protein, were concurrently evaluated, as were responses to GM-CSF, a component of the PA2024 fusion protein used in the preparation of sipuleucel-T.Samples were evaluated for antigen-specific IFNy or granzyme B secretion by ELISPOT, and the detection of statistically significant antigen-specific responses, that were at least 3-fold over the baseline value, and detectable more than once post-treatment, were used to define immune response to a particular antigen. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Measure Prostate-specific Antigen (PSA) Doubling Time | 12 months | PSA doubling times were calculated from PSA values obtained up to 6 months from day 1 of study treatment. An increase in the PSA doubling time to at least double the baseline value will be defined as a PSA doubling time response. |
| Progression-free Survival | 12 months | Percentage of patients without radiographic progression at 12 months. |
| Time to Radiographic Disease Progression | 12 months | Time to radiographic progression using staging obtained at month 3 as baseline for evaluation. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Logistic Regression Analysis Will be Conducted to Evaluate Whether PAP-specific Immune Response is Associated With Prolonged (1-year) Progression-free Survival. | 12 months | Not performed because no progression free survival at one year. |
| Logistic Regression Analysis Will be Conducted to Evaluate Whether Baseline Immune Responses Predict for Immune Responses Elicited/Augmented Following Treatment With Sipuleucel-T +/- DNA Vaccine. | 12 months | Not performed because no progression free survival at one year. |
| The Detection of Antigen Spread to Other Prostate Associated Antigens, and the Identification of Specific Antigens Recognized, Will be Analyzed Descriptively. | 12 months | Not performed because no progression free survival at one year. |
| Overall Survival: Median Time to Death From Any Cause | up to approximately 5 years | Overall survival is defined as the time interval from randomization to death from any cause or to the last follow-up in censored patients. |
| Number of Circulating Tumor Cells | 6 months | — |
| PAP-specific Antibody and T-cell Immune Responses Following Treatment With Sipuleucel-T and DNA Vaccine | 12 months | A response resulting from immunization was defined as a PAP-specific response detectable more than once post-treatment that was both significant (compared to media only control), at least 3-fold higher than the pre-treatment value, and with a frequency\> 1:100,000 PBMC. An antibody response was defined as any increase in titer over baseline. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sipuleucel-T Patients receive sipuleucel-T IV on weeks 0, 2, and 4.
sipuleucel-T: Given IV | 9 |
| Sipuleucel-T With DNA Vaccine Patients receive sipuleucel-T as patients in arm I and pTVG-HP plasmid DNA vaccine ID on weeks 6, 8, 10, and 12, and then at 6 and 9 months.
sipuleucel-T: Given IV
DNA Vaccine: Given ID | 9 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 3 | 4 |
Baseline characteristics
| Characteristic | Sipuleucel-T | Sipuleucel-T With DNA Vaccine | Total |
|---|---|---|---|
| Age, Continuous | 75 years | 72 years | 74 years |
| Baseline PSA doubling time (months) | 2.8 months | 2.2 months | 2.55 months |
| Baseline PSA (ng/mL) | 32.6 ng/mL | 11.2 ng/mL | 16.25 ng/mL |
| ECOG Performance Status 0 | 9 Participants | 8 Participants | 17 Participants |
| ECOG Performance Status 1 | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 9 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Gleason score 7 | 3 Participants | 4 Participants | 7 Participants |
| Gleason score < 7 | 1 Participants | 2 Participants | 3 Participants |
| Gleason score 8 | 0 Participants | 2 Participants | 2 Participants |
| Gleason score >/= 9 | 5 Participants | 0 Participants | 5 Participants |
| Gleason score Unknown | 0 Participants | 1 Participants | 1 Participants |
| Metastatic sites Bone | 2 Participants | 5 Participants | 7 Participants |
| Metastatic sites Distant lymph nodes | 6 Participants | 4 Participants | 10 Participants |
| Metastatic sites Visceral | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 9 Participants | 18 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 9 | 8 / 9 |
| other Total, other adverse events | 9 / 9 | 9 / 9 |
| serious Total, serious adverse events | 1 / 9 | 2 / 9 |
Outcome results
Primary
Number of Participants With Immune Response Following Treatment
The primary immunological goal of this study was to determine whether booster immunizations with a DNA vaccine encoding PAP could augment the number of PAP-specific effector and memory T cells following treatment with sipuleucel-T, or prolong the duration of detectable T-cell response. All subjects received a tetanus booster immunization prior to beginning the immunization series, providing a separate test of an individual's immune responsiveness. Responses to PSA, a non-target prostate specific protein, were concurrently evaluated, as were responses to GM-CSF, a component of the PA2024 fusion protein used in the preparation of sipuleucel-T.Samples were evaluated for antigen-specific IFNy or granzyme B secretion by ELISPOT, and the detection of statistically significant antigen-specific responses, that were at least 3-fold over the baseline value, and detectable more than once post-treatment, were used to define immune response to a particular antigen.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sipuleucel-T | Number of Participants With Immune Response Following Treatment | 6 Participants |
| Sipuleucel-T With DNA Vaccine | Number of Participants With Immune Response Following Treatment | 5 Participants |
Secondary
Measure Prostate-specific Antigen (PSA) Doubling Time
PSA doubling times were calculated from PSA values obtained up to 6 months from day 1 of study treatment. An increase in the PSA doubling time to at least double the baseline value will be defined as a PSA doubling time response.
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sipuleucel-T | Measure Prostate-specific Antigen (PSA) Doubling Time | 2.5 months |
| Sipuleucel-T With DNA Vaccine | Measure Prostate-specific Antigen (PSA) Doubling Time | 2.6 months |
Secondary
Progression-free Survival
Percentage of patients without radiographic progression at 12 months.
Time frame: 12 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sipuleucel-T | Progression-free Survival | 0 Participants |
| Sipuleucel-T With DNA Vaccine | Progression-free Survival | 0 Participants |
Secondary
Time to Radiographic Disease Progression
Time to radiographic progression using staging obtained at month 3 as baseline for evaluation.
Time frame: 12 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sipuleucel-T | Time to Radiographic Disease Progression | 161 days |
| Sipuleucel-T With DNA Vaccine | Time to Radiographic Disease Progression | 164 days |
Other Pre-specified
Logistic Regression Analysis Will be Conducted to Evaluate Whether Baseline Immune Responses Predict for Immune Responses Elicited/Augmented Following Treatment With Sipuleucel-T +/- DNA Vaccine.
Not performed because no progression free survival at one year.
Time frame: 12 months
Population: This outcome measure was not determined because there was no progression-free survival at one-year.
Other Pre-specified
Logistic Regression Analysis Will be Conducted to Evaluate Whether PAP-specific Immune Response is Associated With Prolonged (1-year) Progression-free Survival.
Not performed because no progression free survival at one year.
Time frame: 12 months
Population: This outcome measure was not determined because there was no progression free survival at one-year.
Other Pre-specified
Number of Circulating Tumor Cells
Time frame: 6 months
Population: This outcome measure was not determined because there was no progression free survival at one-year.
Other Pre-specified
Overall Survival: Median Time to Death From Any Cause
Overall survival is defined as the time interval from randomization to death from any cause or to the last follow-up in censored patients.
Time frame: up to approximately 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sipuleucel-T | Overall Survival: Median Time to Death From Any Cause | 32.3 months |
| Sipuleucel-T With DNA Vaccine | Overall Survival: Median Time to Death From Any Cause | 29.6 months |
p-value: 0.906Log Rank
Other Pre-specified
PAP-specific Antibody and T-cell Immune Responses Following Treatment With Sipuleucel-T and DNA Vaccine
A response resulting from immunization was defined as a PAP-specific response detectable more than once post-treatment that was both significant (compared to media only control), at least 3-fold higher than the pre-treatment value, and with a frequency\> 1:100,000 PBMC. An antibody response was defined as any increase in titer over baseline.
Time frame: 12 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Sipuleucel-T | PAP-specific Antibody and T-cell Immune Responses Following Treatment With Sipuleucel-T and DNA Vaccine | Interferon Gamma Response | 3 Participants |
| Sipuleucel-T | PAP-specific Antibody and T-cell Immune Responses Following Treatment With Sipuleucel-T and DNA Vaccine | Granzyme B | 4 Participants |
| Sipuleucel-T | PAP-specific Antibody and T-cell Immune Responses Following Treatment With Sipuleucel-T and DNA Vaccine | Antibody Response | 3 Participants |
| Sipuleucel-T With DNA Vaccine | PAP-specific Antibody and T-cell Immune Responses Following Treatment With Sipuleucel-T and DNA Vaccine | Interferon Gamma Response | 2 Participants |
| Sipuleucel-T With DNA Vaccine | PAP-specific Antibody and T-cell Immune Responses Following Treatment With Sipuleucel-T and DNA Vaccine | Granzyme B | 4 Participants |
| Sipuleucel-T With DNA Vaccine | PAP-specific Antibody and T-cell Immune Responses Following Treatment With Sipuleucel-T and DNA Vaccine | Antibody Response | 5 Participants |
Other Pre-specified
The Detection of Antigen Spread to Other Prostate Associated Antigens, and the Identification of Specific Antigens Recognized, Will be Analyzed Descriptively.
Not performed because no progression free survival at one year.
Time frame: 12 months
Population: This outcome measure was not determined because there was no progression free survival at one-year.