Sipuleucel-T Manufacturing Demonstration Study

Prostate Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01477749
• Other study ID #: P11-1
• Secondary ID: 2011-001192-39
• Status: Completed
• Phase: Phase 2
• First received: November 19, 2011
• Last updated: November 4, 2015
• Start date: June 2012
• Est. completion date: June 2014

Study information

• Verified date: November 2015
• Source: Dendreon
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyUnited Kingdom: National Health Service
• Study type: Interventional

Clinical Trial Summary

To demonstrate that sipuleucel-T can be successfully manufactured for subjects with metastatic castrate resistant prostate cancer (mCRPC) at a European manufacturing facility.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 47
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Cancer of Prostate
• Cancer of the Prostate
• Neoplasms
• Neoplasms, Prostate
• Neoplasms, Prostatic
• Prostate Cancer
• Prostate Neoplasms
• Prostatic Cancer
• Prostatic Neoplasms

Intervention

Biological:
• 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.

Locations

Country	Name	City	State
Austria	Ludwig Boltzmann-Institute for Applied Cancer Research	Wien
France	Department of Cancer Medicine and Genitourinary Oncology Group Institut Gustave Roussy (IGR) Département de médicine	Vaillant	Villejuif Cedex
Netherlands	Radboud University Nijmegen; UMC St Radboud Hospital; Faculteit der Medische Wetenschappen, Urologie	Nijmegen	Gelderland
United Kingdom	Barts Cancer Institute - a Cancer Research UK Centre of Excellence, Queen Mary University of London	London

Sponsors (1)

Lead Sponsor	Collaborator
Dendreon

Countries where clinical trial is conducted

Austria,  France,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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	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)	No
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.	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)	No
Primary	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)	No
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.	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)	No