Prostate Cancer
Conditions
Keywords
adenocarcinoma of the prostate, stage IV prostate cancer, recurrent prostate cancer
Brief summary
Rationale: Vaccines may make the body build an immune response to kill tumor cells. It is not yet known if vaccine therapy is effective for prostate cancer. Purpose: Randomized phase III trial to determine the effectiveness of vaccine therapy in treating patients who have metastatic prostate cancer that has not responded to hormone therapy.
Detailed description
Objectives: I. Compare the time to progression, time to development of disease-related pain, and incidence of grade 3 or worse treatment-related adverse events in patients with asymptomatic metastatic hormone refractory adenocarcinoma of the prostate treated with APC8015 versus control infusion. II. Compare response rate and duration of response in these patients. Outline: This is a randomized study. Patients are randomized to one of two treatment arms. Arm I: Autologous dendritic cell precursors (ADCP) are harvested on weeks 0, 2, and 4. Patients receive APC8015 comprised of ADCP activated with prostatic acid phosphatase-sargramostim (GM-CSF) fusion protein IV over 30 minutes beginning 2 days after each harvest for a total of 3 infusions. Arm II: ADCP are harvested as in arm I. Patients receive unactivated ADCP IV over 30 minutes beginning 2 days after each harvest for a total of 3 infusions. Pain is assessed weekly for up to 3 years or until 4 weeks after objective disease progression. Patients are followed monthly for up to 3 years or until disease progression. At the time of disease progression, patients treated on arm II may receive treatment on Protocol D9903. Projected Accrual: A total of 120 patients (80 in arm I and 40 in arm II) will be accrued for this study.
Interventions
BIOLOGICALsipuleucel-T
Autologous peripheral blood mononuclear cells, including antigen presenting cells, that have been activated in vitro with a recombinant fusion protein, PAP-GM-CSF. Treatment consist of 3 doses administered approximately 2 weeks apart.
BIOLOGICALPlacebo
Approximately one-third of the autologous quiescent antigen presenting cells (APCs) prepared from a single leukapheresis procedure. A course of therapy consists of 3 complete doses given at approximately 2-week intervals.
Sponsors
Dendreon
Study design
Allocation
RANDOMIZED
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
include: * Metastatic disease as evidenced by soft tissue and/or bony metastases. * Baseline PSA value of at least 5 ng/mL. All subjects must have stable or rising PSA. * Tumor progression after hormonal therapy. * Hormonal therapy consisting of castration by orchiectomy or LHRH agonists for treatment of prostate cancer. Castration levels of testosterone (\< 50 ng/dL) must be documented for all subjects including subjects who underwent orchiectomy as therapy for cancer of the prostate. * A subject is eligible if he initially responded to antiandrogen withdrawal (\> 25% decrease in PSA) but at the time of registration demonstrated tumor progression. A subject is eligible if he failed to respond to antiandrogen withdrawal. * Subjects have no cancer-related pain and do not regularly require analgesics for cancer-related pain. * ECOG Performance Status of 0 or 1. * Life expectancy of at least 16 weeks. * Adequate hematologic, renal, and liver function.
Exclusion criteria
include: * Visceral organ metastases (e.g., liver, lung, brain) or cytologically positive effusions (e.g., pleural effusions or ascites). * Metastatic disease expected to be in need of radiation therapy within 4 months. * Concurrent therapy with experimental agents. * Systemic corticosteroids at doses greater than 40 mg hydrocortisone per day for any reason other than treatment of prostate cancer within the previous 6 months without prior approval. Please note that there are additional eligibility criteria. The study center will determine if you meet all of the criteria.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Objective Disease Progression | 36 months from randomization | The time to objective disease progression in patients with asymptomatic metastatic hormone-refractory prostate cancer treated with APC8015 (sipuleucel-T). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | From randomization to 36 months | Overall Survival |
Countries
United States
Participant flow
Recruitment details
Participants were randomized between January 2000 and September 2004 across 16 clinical trial sites.
Pre-assignment details
Participants were screened for evaluation of subject eligibility and performance of baseline tests/procedures.
Participants by arm
| Arm | Count |
|---|---|
| Sipuleucel-T All subjects randomized to receive sipuleucel-T. Autologous peripheral blood mononuclear cells, including antigen presenting cells, that have been activated in vitro with a recombinant fusion protein, PAP-GM-CSF. Treatment consist of 3 doses administered approximately 2 weeks apart. | 82 |
| Placebo All subjects randomized to receive placebo. Approximately one-third of the quiescent APCs prepared from a single leukapheresis procedure. | 45 |
| Total | 127 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 54 | 40 |
| Overall Study | Patient Refused to Continue | 2 | 1 |
| Overall Study | Site Closure | 1 | 0 |
Baseline characteristics
| Characteristic | Sipuleucel-T | Placebo | Total |
|---|---|---|---|
| Age Continuous | 72.1 years STANDARD_DEVIATION 8.1 | 71.1 years STANDARD_DEVIATION 8.3 | 71.7 years STANDARD_DEVIATION 8.1 |
| Age, Customized | 73.0 Years (Min, Max) | 71.0 Years (Min, Max) | 73.0 Years (Min, Max) |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 82 Participants | 45 Participants | 127 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 82 / 82 | 44 / 45 |
| serious Total, serious adverse events | 22 / 82 | 8 / 45 |
Outcome results
Primary
Time to Objective Disease Progression
The time to objective disease progression in patients with asymptomatic metastatic hormone-refractory prostate cancer treated with APC8015 (sipuleucel-T).
Time frame: 36 months from randomization
Population: all randomized participants
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sipuleucel-T | Time to Objective Disease Progression | 11.7 Weeks |
| Placebo | Time to Objective Disease Progression | 10.0 Weeks |
p-value: 0.05295% CI: [0.99, 2.11]Log Rank
p-value: 0.05295% CI: [0.47, 1.01]Log Rank
Secondary
Overall Survival
Overall Survival
Time frame: From randomization to 36 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sipuleucel-T | Overall Survival | 25.9 Months |
| Placebo | Overall Survival | 21.4 Months |
Comparison: ITT Population - all randomized participantsp-value: 0.0195% CI: [1.13, 2.58]Log Rank
Comparison: ITT Population - all randomized participants.p-value: 0.0195% CI: [0.388, 0.884]Log Rank