Prostate Cancer
Conditions
Keywords
cancer, prostate cancer, prostatectomy, PSA, sipuleucel-T, PROVENGE, APC8015, non-metastatic, nonmetastatic, androgen-sensitive, androgen sensitive, biochemical recurrence, biochemically recurrent, immune therapy, immunotherapy, vaccine, dendritic cells, antigen-presenting cells, antigen presenting cells, cancer vaccine, therapeutic vaccine, therapeutic cancer vaccine, biologic, booster
Brief summary
The PROTECT-PROvenge Treatment and Early Cancer Treatment trial was a Phase III trial for patients with hormone sensitive prostate cancer. The study was conducted at over 15 participating centers throughout the US. The purpose of the study was to determine if sipuleucel-T was effective for treatment of early stage, non-metastatic prostate cancer. The study compared the active vaccine to control to determine whether the product delayed the time until cancer progression.
Detailed description
This was a prospective, double blind, controlled, randomized trial of immunotherapy with prostatic acid phosphatase (PAP)-loaded autologous antigen presenting cells (APCs), in subjects with non metastatic prostate cancer. Subjects that qualified for this study were men who had previously undergone a prostatectomy and whose only sign of disease recurrence was a rise in serum prostate specific antigen (PSA). The primary objectives were to compare the time to biochemical failure (BF, PSA greater than or equal to 3 ng/mL) between sipuleucel-T (treatment group) and control, and to study the safety of sipuleucel-T. Following short-term open-label treatment with a luteinizing hormone-releasing hormone-analogue (LHRH-a), Subjects completed a checklist designed to compare androgen suppression-related side effects during periods with and without androgen suppression. Subjects who achieved a PSA of \< 1 ng/ml were randomized to blinded treatment assignments of either sipuleucel-T or control in a 2:1 ratio. Following randomization, subjects underwent 3 leukapheresis procedures on alternate weeks (Weeks 0, 2, and 4). Approximately three days following each leukapheresis procedure, subjects received an infusion of either sipuleucel-T or control. At the time BF was confirmed, subjects were eligible for a booster infusion. The booster process consisted of 1 leukapheresis procedure followed by 1 infusion of sipuleucel-T. The booster process, in effect under protocol amendment 5, differed from the previous booster process that consisted of 1 infusion of the same treatment assigned at randomization (sipuleucel-T or control). Subjects continued to be observed until DF was confirmed by bone scan or computed tomography (CT) scan, or other imaging modalities as clinically indicated. After confirmed DF, subjects were followed by telephone every 6 months for safety and survival, treatment-related AEs, any CVEs, or new therapies for prostate cancer.
Interventions
OTHERControl
Autologous cellular product consisting of antigen presenting cells (APCs) prepared in the absence of PA2024 antigen.
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).
Sponsors
Dendreon
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
for the Run-In Phase (Week -13) * Histologic diagnosis of adenocarcinoma of the prostate. * Within at least 3 months, but not more than 10 years, prior to initiation of the run-in phase with LHRH-a depot, the subject has undergone a radical prostatectomy for Stage T1b - T3c, N0 - N1, Nx, or M0 disease Subjects who experienced their first PSA recurrence within 2 years post completion of initial therapy of curative intent was eligible without consideration of the Gleason score of the tumor specimen. Subjects who experienced their first PSA relapse between 2 and 10 years post completion of initial therapy of curative intent was eligible only if the Gleason score of the tumor specimen was ≥ 7. * Therapeutic PSA response to primary therapy was below 0.4 ng/mL. * Tumor specimen positive for PAP. * PSA relapse while not currently receiving androgen ablation therapy. * If androgen ablation was given for a previous PSA relapse, PSA must have increased to a level at least 25% above the nadir observed while on this therapy, and to an absolute level of at least 3 ng/mL. * Subjects who had been treated with adjuvant or salvage radiation following radical prostatectomy, or with either LHRH-a (e.g., leuprolide acetate or goserelin acetate) or non-steroidal anti-androgen therapy (e.g., bicalutamide 150 mg/day) for a prior PSA relapse, may enter the study provided: Post-prostatectomy PSA was never ≥ 20 ng/mL; PSA was not rising while subject received hormonal therapy, and; For any hormonal therapy received, the last effective day of androgen deprivation was at least 6 months prior to the date of LHRH-a depot placement. * Confirmed Stage M0 disease. * Estimated life expectancy of at least 1 year. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. * Ability to understand the trial procedures and requirements. * ≥ 18 and ≤ 80 years of age. * Ability to understand and willingness to sign an informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Biochemical Failure Cumulative Incidence Percentile | Every 3 months post-infusion | Time to Biochemical Failure (TTBF) was the pre-specified primary endpoint of this trial. The biochemical failure threshold was based on evidence that prostate specific antigen (PSA) had become ≥ 3 ng/mL |
| Number of Subjects That Met Biochemical Failure Status | Every 3 months post-infusion | time to biochemical Failure (TTBF) was the pre-scpecified primary endpoint of this trial. The biochemical failure threshold was based on evidence that prostate specific antigen (PSA) had become ≥ 3 ng/mL. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sipuleucel-T Provenge
Provenge: Biologic: autologous cellular product consisting of antigen presenting cells (APCs) activated with PA2024, a recombinant fusion protein composed of PAP, linked to GM-CSF | 117 |
| Control Control
Control: Autologous cellular product consisting of antigen presenting cells (APCs) prepared in the absence of PA2024 antigen | 59 |
| Total | 176 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Long-term Follow-up | Closure of Study | 8 | 4 |
| Long-term Follow-up | Completed Protocol Visits | 6 | 2 |
| Long-term Follow-up | Other | 5 | 0 |
| Long-term Follow-up | Patient refused to continue | 2 | 0 |
| Surveillance Phase | Closure of study | 5 | 6 |
| Surveillance Phase | Completed Protocol Visits | 3 | 2 |
| Surveillance Phase | Death | 0 | 1 |
| Surveillance Phase | Intercurrent Illness | 2 | 0 |
| Surveillance Phase | Lost to Follow-up | 2 | 1 |
| Surveillance Phase | Other | 5 | 5 |
| Surveillance Phase | Patient refused to continue | 22 | 14 |
| Surveillance Phase | Protocol Violation | 0 | 1 |
| Surveillance Phase | Withdrawal by Subject | 4 | 1 |
| Treatment Phase 1 | Adverse Event | 2 | 0 |
| Treatment Phase 1 | Closure of Study | 3 | 2 |
| Treatment Phase 1 | Completed Protocol Visits | 3 | 6 |
| Treatment Phase 1 | Death | 0 | 1 |
| Treatment Phase 1 | Disease Progression | 1 | 0 |
| Treatment Phase 1 | Intercurrent Illness | 1 | 1 |
| Treatment Phase 1 | Lost to Follow-up | 0 | 1 |
| Treatment Phase 1 | Other | 4 | 2 |
| Treatment Phase 1 | Patient Refused to Continue | 17 | 2 |
| Treatment Phase 1 | Protocol Violation | 1 | 0 |
| Treatment Phase 1 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Sipuleucel-T | Total | Control |
|---|---|---|---|
| Age, Continuous | 64.4 years STANDARD_DEVIATION 7.4 | 64.7 years STANDARD_DEVIATION 7.18 | 65.2 years STANDARD_DEVIATION 6.75 |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 0=Fully Active; No restrictions. | 109 Participants | 166 Participants | 57 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG 1= Restricted Strenuous Activity | 6 Participants | 7 Participants | 1 Participants |
| Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG Missing | 2 Participants | 3 Participants | 1 Participants |
| Gleason Score Gleason Score ≤ 6 | 20 Participants | 33 Participants | 13 Participants |
| Gleason Score Gleason Score =7 | 69 Participants | 103 Participants | 34 Participants |
| Gleason Score Gleason Score ≥ 8 | 28 Participants | 40 Participants | 12 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 | 9 Participants | 12 Participants | 3 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 | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 107 Participants | 162 Participants | 55 Participants |
| Region of Enrollment United States | 117 Participants | 176 Participants | 59 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 117 Participants | 176 Participants | 59 Participants |
| Time from diagnosis to randomization | 5.84 years STANDARD_DEVIATION 2.76 | 6.01 years STANDARD_DEVIATION 2.76 | 6.34 years STANDARD_DEVIATION 2.76 |
| Weight | 90.45 Kg STANDARD_DEVIATION 15.52 | 90.21 Kg STANDARD_DEVIATION 14.95 | 89.70 Kg STANDARD_DEVIATION 13.85 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 20 / 116 | 9 / 59 |
| other Total, other adverse events | 114 / 116 | 57 / 59 |
| serious Total, serious adverse events | 31 / 116 | 19 / 59 |
Outcome results
Primary
Number of Subjects That Met Biochemical Failure Status
time to biochemical Failure (TTBF) was the pre-scpecified primary endpoint of this trial. The biochemical failure threshold was based on evidence that prostate specific antigen (PSA) had become ≥ 3 ng/mL.
Time frame: Every 3 months post-infusion
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sipuleucel-T | Number of Subjects That Met Biochemical Failure Status | 85 Participants |
| Control | Number of Subjects That Met Biochemical Failure Status | 45 Participants |
Primary
Time to Biochemical Failure Cumulative Incidence Percentile
Time to Biochemical Failure (TTBF) was the pre-specified primary endpoint of this trial. The biochemical failure threshold was based on evidence that prostate specific antigen (PSA) had become ≥ 3 ng/mL
Time frame: Every 3 months post-infusion
Population: Number of subjects that met biochemical failure criteria.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Sipuleucel-T | Time to Biochemical Failure Cumulative Incidence Percentile | 25th Cumulative Incidence Percentile | 7.6 Months |
| Sipuleucel-T | Time to Biochemical Failure Cumulative Incidence Percentile | 50th Cumulative Incidence Percentile | 14.9 Months |
| Sipuleucel-T | Time to Biochemical Failure Cumulative Incidence Percentile | 75th Cumulative Incidence Percentile | 22.9 Months |
| Control | Time to Biochemical Failure Cumulative Incidence Percentile | 25th Cumulative Incidence Percentile | 6.8 Months |
| Control | Time to Biochemical Failure Cumulative Incidence Percentile | 50th Cumulative Incidence Percentile | 12.4 Months |
| Control | Time to Biochemical Failure Cumulative Incidence Percentile | 75th Cumulative Incidence Percentile | 24.6 Months |
p-value: 0.6595% CI: [0.693, 1.433]Log Rank