Sipuleucel-T Manufacturing Demonstration Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-Label Study Study of Sipuleucel-T in European Men With Metastatic, Castrate Resistant Prostate Cancer

Conditions
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Cancer of Prostate, Cancer of the Prostate, Neoplasms, Prostate, Neoplasms, Prostatic, Prostate Cancer, Prostate Neoplasms, Prostatic Cancer

Intervention / Treatment
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* Biological: sipuleucel-T


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sipuleucel-T<br>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. | Biological: sipuleucel-T<br>* 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.<br>* Other names: APC8015;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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) | 
| 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. | 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) | 
| Cumulative Total Nucleated Cell (TNC) Count | Descriptive summarization of the cumulative sum of TNC counts across infusions | 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 (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. | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prostate, prostate cancer, immune therapy, immunotherapy, vaccine, dendritic cells, antigen-presenting cells, antigen presenting cells, cancer vaccine, PSA, prostatic adenocarcinoma