Sipuleucel-T Manufacturing Demonstration Study

Phase 2

Completed

• Conditions: Prostate Neoplasms; Neoplasms, Prostate; Neoplasms, Prostatic; Cancer of the Prostate; Prostatic Cancer; Prostate Cancer; Cancer of Prostate
• Interventions: Biological: sipuleucel-T

• Registration Number: NCT01477749
• Lead Sponsor: Dendreon

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.

Study Timeline

• Study First Submitted: 2011-11-19
• Study First Submitted QC: 2011-11-19
• Study First Posted: 2011-11-23
• Study Start: 2012-06
• Primary Completion: 2014-06
• Study Completion: 2014-06
• Results First Submitted: 2015-06-10
• Status Verified: 2015-11
• Results First Submitted QC: 2015-11-04
• Last Update Submitted: 2015-11-04
• Results First Posted: 2015-12-09
• Last Update Posted: 2015-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 47

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
sipuleucel-T	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.

Primary Outcome Measures

Name	Time	Method
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
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.
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.
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

Trial Locations

Locations (4)

Ludwig Boltzmann-Institute for Applied Cancer Research; 🇦🇹 Wien, Austria

Department of Cancer Medicine and Genitourinary Oncology Group Institut Gustave Roussy (IGR) Département de médicine; 🇫🇷 Vaillant, Villejuif Cedex, France

Radboud University Nijmegen; UMC St Radboud Hospital; Faculteit der Medische Wetenschappen, Urologie; 🇳🇱 Nijmegen, Gelderland, Netherlands

Barts Cancer Institute - a Cancer Research UK Centre of Excellence, Queen Mary University of London; 🇬🇧 London, United Kingdom