Clinical trial NCT01477749: Sipuleucel-T Manufacturing Demonstration Study
Official title: An Open-Label Study Study of Sipuleucel-T in European Men With Metastatic, Castrate Resistant Prostate Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cancer of Prostate
Cancer of the Prostate
Neoplasms, Prostate
Neoplasms, Prostatic
Prostate Cancer
Prostate Neoplasms
Prostatic Cancer
Keywords: prostate cancer
prostate
immune therapy
immunotherapy
vaccine
dendritic cells
antigen-presenting cells
antigen presenting cells
cancer vaccine
PSA
prostatic adenocarcinoma
Lead sponsor: Dendreon
Sponsor class: INDUSTRY
First posted: 2011-11-23
Enrollment: 47
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Cumulative CD54+ Cell Count
timeFrame: 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)
measure: Cumulative CD54 Upregulation
timeFrame: 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)
measure: Cumulative Total Nucleated Cell (TNC) Count
timeFrame: 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)
measure: Product Viability (Percentage)
timeFrame: 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)
Secondary outcomes:
Other outcomes:
Locations:
city: Wien
country: Austria
facility: Ludwig Boltzmann-Institute for Applied Cancer Research
city: Vaillant
country: France
facility: Department of Cancer Medicine and Genitourinary Oncology Group Institut Gustave Roussy (IGR) Département de médicine
state: Villejuif Cedex
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen; UMC St Radboud Hospital; Faculteit der Medische Wetenschappen, Urologie
state: Gelderland
city: London
country: United Kingdom
facility: Barts Cancer Institute - a Cancer Research UK Centre of Excellence, Queen Mary University of London
Study officials:
affiliation: Dendreon
name: Andrew Stubbs, PhD
role: STUDY_DIRECTOR
References: