Prostate Cancer, Prostatic Adenocarcinoma, Prostatic Neoplasm
Conditions
Keywords
Immune therapy, Cancer vaccine, Therapeutic vaccine, Therapeutic cancer vaccine, Vaccine, Dendritic cells, PSA, Androgen deprivation therapy, Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms, Prostatic Diseases, Androgens, Hormones, Adenocarcinoma, Carcinoma, Neoplasms, Glandular and Epithelial, Immunology, Hormone therapy, Immunotherapy, Luteinizing hormone-releasing hormone (LHRH)
Brief summary
The main purpose of this study was to determine whether ADT started before or after sipuleucel-T led to a better immune system response. This study also evaluated the safety of sipuleucel-T and ADT treatment, immune system responses over time, the characteristics of sipuleucel-T, and changes in prostate specific antigen (PSA) values over time.
Detailed description
Multicenter, randomized, open-label study, with subjects allocated (1:1) to 1 of 2 study arms, using a stratified randomization based on: • Prostate-specific antigen doubling time (PSADT): ≤ 3 months or \> 3 months and ≤ 12 months. • Primary therapy: radical prostatectomy (RP) or radiation, including brachytherapy, (XRT) or RP + XRT. Arm 1: Subjects received one infusion of sipuleucel-T every two weeks for a total of three infusions. Two weeks after the third sipuleucel-T infusion, subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg). An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT. Arm 2: Subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg) 12 weeks before infusion 1 of sipuleucel-T. An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT. Twelve weeks after the initial leuprolide 45 mg depot injection, subjects began one infusion of sipuleucel-T every two weeks for a total of three infusions. Cellular and humoral immune responses were assessed for Arm 2 subjects at 12, 8, and 4 weeks pre infusion 1, and in all subjects (both arms) at pre-leukapheresis 1, 2, and 3, and post-infusion 1, 2 and 3, and at the following time points after the third infusion: Weeks 2, 6, and 12 and Months 6, 9, 12, 15, 18, 21, and 24. Safety assessments included adverse event (AE) monitoring, laboratory tests (complete blood count (CBC) and serum chemistry), vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, physical examination, as well PSA and testosterone monitoring. The study was complete at the 27-Month visit for Arm 1 and the 24-Month visit for Arm 2.
Interventions
BIOLOGICALsipuleucel-T
Sipuleucel-T is an autologous cellular product consisting of antigen presenting cells (APCs) activated with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).
DRUGleuprolide acetate
45.0 mg depot injection, 2 doses 6 months apart
Sponsors
Dendreon
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
* Hormone-sensitive prostate cancer * Non-metastatic disease, as evidenced by negative bone scan or computed tomography of the abdomen and pelvis * ECOG performance status ≤ 1 * Histologically documented prostate cancer * Prior primary therapy for prostate cancer * Rising PSA with a PSADT of ≤ 12 months * Testosterone ≥ 200 ng/dL ≤ 28 days of registration * Adequate hematologic, renal, and liver function * Must live in a permanent residence within a comfortable driving distance (round-trip within one day) to the clinical research site
Exclusion criteria
* Requires systemic ongoing immunosuppressive therapy * History of allergic reactions attributed to compounds of similar chemical or biologic composition to sipuleucel-T or GM-CSF * Prior sipuleucel-T therapy * Prior ADT therapy ≤ 6 months prior to registration or ≥ 6 months duration in total * If subject has a history of any other stage III/IV malignancy, the subject must be disease free and off any malignancy-related treatment for at least 10 years. If the subject has a history of any stage I-II malignancy, the subject must be disease free and off any malignancy-related treatment for at least 5 years. * Prior experimental immunotherapy or on an experimental clinical trial within 1 year * Received denosumab or XRT ≤ 6 months prior to registration * Received chemotherapy or GM-CSF ≤ 90 days prior to registration * Received any of the following medications or interventions ≤ 28 days prior to registration * major surgery requiring general anesthesia * systemic immunosuppressive therapy * other prescription treatment for prostate cancer * Active infection within 1 week of registration * Likely to receive XRT or surgery for prostate cancer during the study period * Any medical intervention, any other condition, or any circumstances that could compromise the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immune Response at Month 24 as Evaluated by IFN-γ ELISPOT Specific for PA2024 | PA2024 ELISPOT counts at Month 24 | Immune response at month 24 as evaluated by IFN-γ ELISPOT specific for PA2024 following sipuleucel-T/ADT treatment regimens to determine if order of administration impacted immune response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Immune Response As Evaluated by IFN-γ ELISPOT Specific for PA2024 | Month 24 | A participant was considered to have an immune response it the post-baseline PA2024-specific IFN-g ELISPOT count was \>18 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: Sipuleucel-T Followed by ADT Subjects received one infusion of sipuleucel-T every two weeks for a total of three infusions. Two weeks after the third sipuleucel-T infusion, subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg). An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT. | 34 |
| Arm 2: ADT Followed by Sipuleucel-T Subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg) 12 weeks before infusion 1 of sipuleucel-T. An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT. Twelve weeks after the initial leuprolide 45 mg depot injection, subjects began one infusion of sipuleucel-T every two weeks for a total of three infusions. | 34 |
| Total | 68 |
Baseline characteristics
| Characteristic | Arm 1: Sipuleucel-T Followed by ADT | Total | Arm 2: ADT Followed by Sipuleucel-T |
|---|---|---|---|
| Age, Continuous | 65.4 years STANDARD_DEVIATION 1.4 | 65.8 years STANDARD_DEVIATION 0.9 | 66.2 years STANDARD_DEVIATION 1.1 |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG 0=Fully Active; No restrictions. | 33 Participants | 67 Participants | 34 Participants |
| Eastern Cooperative Oncology Group (ECOG) performance status ECOG 1= Restricted Strenuous Activity | 1 Participants | 1 Participants | 0 Participants |
| Gleason Score Gleason Score ≤ 6 | 3 Participants | 7 Participants | 4 Participants |
| Gleason Score Gleason Score = 7 | 23 Participants | 44 Participants | 21 Participants |
| Gleason Score Gleason Score ≥ 8 | 8 Participants | 17 Participants | 9 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 | 34 Participants | 68 Participants | 34 Participants |
| Region of Enrollment United States | 34 Participants | 68 Participants | 34 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 34 Participants | 68 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 34 | 34 / 34 |
| serious Total, serious adverse events | 1 / 34 | 5 / 34 |
Outcome results
Primary
Immune Response at Month 24 as Evaluated by IFN-γ ELISPOT Specific for PA2024
Immune response at month 24 as evaluated by IFN-γ ELISPOT specific for PA2024 following sipuleucel-T/ADT treatment regimens to determine if order of administration impacted immune response.
Time frame: PA2024 ELISPOT counts at Month 24
Population: The immune response population was defined as all randomized subjects who received 3 infusions of sipuleucel-T.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1: Sipuleucel-T Followed by ADT | Immune Response at Month 24 as Evaluated by IFN-γ ELISPOT Specific for PA2024 | 81.0 IFN-γ ELISPOT (per 300,000 PBMC) | Standard Error 28 |
| Arm 2: ADT Followed by Sipuleucel-T | Immune Response at Month 24 as Evaluated by IFN-γ ELISPOT Specific for PA2024 | 61.1 IFN-γ ELISPOT (per 300,000 PBMC) | Standard Error 23.7 |
Secondary
Percentage of Participants With Immune Response As Evaluated by IFN-γ ELISPOT Specific for PA2024
A participant was considered to have an immune response it the post-baseline PA2024-specific IFN-g ELISPOT count was \>18
Time frame: Month 24
Population: The immune response population was defined as all randomized subjects who received 3 infusions of sipuleucel-T.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1: Sipuleucel-T Followed by ADT | Percentage of Participants With Immune Response As Evaluated by IFN-γ ELISPOT Specific for PA2024 | 88 percentage of participants |
| Arm 2: ADT Followed by Sipuleucel-T | Percentage of Participants With Immune Response As Evaluated by IFN-γ ELISPOT Specific for PA2024 | 85 percentage of participants |