Cancer of Prostate, Cancer of the Prostate, Neoplasms, Prostate, Neoplasms, Prostatic, Prostate Cancer, Prostate Neoplasms, Prostatic Cancer
Conditions
Keywords
prostate cancer, prostate, immune therapy, immunotherapy, vaccine, dendritic cells, antigen-presenting cells, antigen presenting cells, cancer vaccine, PSA, prostatic adenocarcinoma
Brief summary
To demonstrate that sipuleucel-T can be successfully manufactured for subjects with metastatic castrate resistant prostate cancer (mCRPC) at a European manufacturing facility.
Detailed description
This was an open-label, uncontrolled, multi-center study. Study participants will underwent screening procedures to ensure that they met the inclusion and exclusion criteria. Subjects underwent a standard 1.5 to 2.0 blood volume leukapheresis, followed approximately 3 days later by an infusion of sipuleucel-T. This process was be repeated at approximately 2-week intervals for a total of 3 infusions. In Austria, The Netherlands, and France, a study completion visit occurred between 30 and 37 days post-final infusion, or between 30 and 37 days post-final leukapheresis for subjects not receiving at least 1 infusion. In the UK, a follow-up visit occurred 30 days after the subject's final infusion and a study completion visit occurred 6 months after the subject's final infusion.
Interventions
BIOLOGICALsipuleucel-T
Each dose of sipuleucel-T contains a minimum of 50 million autologous CD54+ cells activated with PAP-GM-CSF. The recommended course of therapy for sipuleucel-T is 3 complete doses, given at approximately 2-week intervals.
Sponsors
Dendreon
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically documented adenocarcinoma of the prostate * Metastatic disease as evidenced by soft tissue and/or bony metastases on bone scan and/or computed tomography (CT) scan of the abdomen and pelvis at any time prior to registration * Castrate resistant prostate cancer * Serum PSA ≤ 5.0 ng/mL * Castration levels of testosterone (≤ 50 ng/dL; ≤ 1.74 nmol/L) achieved via medical or surgical castration. Surgical castration must have occurred at least 3 months prior to registration. * ECOG performance status ≤ 1 * Adequate hematologic, renal, and liver function * Negative serology tests indicating no active infection with human immunodeficiency virus types 1 and 2 (HIV-1/2), human T cell lymphotropic virus types 1 and 2 (HTLV-I/II), and Hepatitis B and C viruses.
Exclusion criteria
* The presence of known brain metastases * A requirement for systemic immunosuppressive therapy for any reason * Treatment with any investigational vaccine within 2 years prior to registration * Any previous treatment with sipuleucel-T * Any previous treatment with ipilimumab (Yervoy\[TM\], MDX-010, or MDX-101) or denosumab (Xgeva\[TM\]) * Pathologic long-bone fractures, imminent pathologic long-bone fracture (cortical erosion on radiography \> 50%), or spinal cord compression * Known malignancies other than prostate cancer that are likely to require treatment within 6 months of registration * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to sipuleucel-T or GM-CSF * More than 2 chemotherapy regimens at any time prior to registration * Treatment with any chemotherapy within 90 days of registration * Received granulocyte colony-stimulating factor (G-CSF) or GM-CSF within 90 days prior to registration * Treatment with any of the following medications or interventions within 28 days of registration: * Systemic corticosteroids. Use of inhaled, intranasal, intra-articular, and topical steroids is acceptable, as is a short course (i.e., ≤ 1 day) of corticosteroids to prevent a reaction to the IV contrast used for CT scans. * Non-steroidal anti-androgens (e.g., bicalutamide, flutamide, or nilutamide) * External beam radiation therapy or major surgery requiring general anesthetic * Any other systemic therapy for prostate cancer including secondary hormonal therapies, such as megestrol acetate (Megace®), diethylstilbestrol (DES), and ketoconazole. Medical castration therapy is not exclusionary. * Immunosuppressive therapy * Treatment with any other investigational product * Any infection requiring parenteral antibiotic therapy or causing fever (temperature \> 100.5°F or 38.1°C) within 7 days prior to registration. * Any medical intervention or other condition which, in the opinion of the Investigator or the Dendreon Medical Monitor, could compromise adherence with study requirements or otherwise compromise the study's objectives.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative CD54+ Cell Count | Before and after culture with PAP-GM-CSF, on Day 3 (first infusion) and on approximately Days 17 and 31 (second and third infusion, respectively) | Descriptive summarization of the cumulative sum of CD54+ counts across infusions. Cumulative CD54 upregulation = CD54 upregulation for infusion 1 + CD54 upregulation for infusion 2 + CD54 upregulation for infusion 3 |
| Cumulative CD54 Upregulation | Before and after culture with PAP-GM-CSF, on Day 3 (first infusion) and on approximately Days 17 and 31 (second and third infusion, respectively) | The increase in surface CD54 on APCs, expressed as an upregulation ratio of the average number of molecules on post-culture versus pre-culture cells. Cumulative CD54 upregulation = CD54 upregulation ratio for infusion 1 + CD54 upregulation ratio for infusion 2 + CD54 upregulation ratio for infusion 3. |
| Cumulative Total Nucleated Cell (TNC) Count | Before and after culture with PAP-GM-CSF, on Day 3 (first infusion) and on approximately Days 17 and 31 (second and third infusion, respectively) | Descriptive summarization of the cumulative sum of TNC counts across infusions |
| Product Viability (Percentage) | Before and after culture with PAP-GM-CSF, on Day 3 (first infusion) and on approximately Days 17 and 31 (second and third infusion, respectively) | Product viability was measured as the percentage of live PBMC in final product for infusion 1, 2, and 3 as measured by a trypan blue assay and are reported for each final product for infusion 1, 2, and 3. |
Countries
Austria, France, Netherlands, United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sipuleucel-T Each dose of sipuleucel-T contains a minimum of 50 million autologous CD54+ cells activated with PAP-GM-CSF. The recommended course of therapy for sipuleucel-T is 3 complete doses, given at approximately 2-week intervals.
sipuleucel-T: Each dose of sipuleucel-T contains a minimum of 50 million autologous CD54+ cells activated with PAP-GM-CSF. The recommended course of therapy for sipuleucel-T is 3 complete doses, given at approximately 2-week intervals. | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 4 |
Baseline characteristics
| Characteristic | Sipuleucel-T |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 35 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants |
| Region of Enrollment Austria | 17 participants |
| Region of Enrollment France | 8 participants |
| Region of Enrollment Netherlands | 15 participants |
| Region of Enrollment United Kingdom | 7 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 40 / 47 |
| serious Total, serious adverse events | 3 / 47 |
Outcome results
Primary
Cumulative CD54+ Cell Count
Descriptive summarization of the cumulative sum of CD54+ counts across infusions. Cumulative CD54 upregulation = CD54 upregulation for infusion 1 + CD54 upregulation for infusion 2 + CD54 upregulation for infusion 3
Time frame: Before and after culture with PAP-GM-CSF, on Day 3 (first infusion) and on approximately Days 17 and 31 (second and third infusion, respectively)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sipuleucel-T | Cumulative CD54+ Cell Count | 1.58 10^9 cells/mL | Standard Error 0.1 |
Primary
Cumulative CD54 Upregulation
The increase in surface CD54 on APCs, expressed as an upregulation ratio of the average number of molecules on post-culture versus pre-culture cells. Cumulative CD54 upregulation = CD54 upregulation ratio for infusion 1 + CD54 upregulation ratio for infusion 2 + CD54 upregulation ratio for infusion 3.
Time frame: Before and after culture with PAP-GM-CSF, on Day 3 (first infusion) and on approximately Days 17 and 31 (second and third infusion, respectively)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sipuleucel-T | Cumulative CD54 Upregulation | 34.10 Ratio | Standard Error 1.24 |
Primary
Cumulative Total Nucleated Cell (TNC) Count
Descriptive summarization of the cumulative sum of TNC counts across infusions
Time frame: Before and after culture with PAP-GM-CSF, on Day 3 (first infusion) and on approximately Days 17 and 31 (second and third infusion, respectively)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sipuleucel-T | Cumulative Total Nucleated Cell (TNC) Count | 12.54 10^9 cells/mL | Standard Error 0.74 |
Primary
Product Viability (Percentage)
Product viability was measured as the percentage of live PBMC in final product for infusion 1, 2, and 3 as measured by a trypan blue assay and are reported for each final product for infusion 1, 2, and 3.
Time frame: Before and after culture with PAP-GM-CSF, on Day 3 (first infusion) and on approximately Days 17 and 31 (second and third infusion, respectively)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sipuleucel-T | Product Viability (Percentage) | 96.75 Percentage of PBMC that are live |