Sipuleucel-T as Neoadjuvant Treatment in Prostate Cancer

Phase 2

Completed

• Conditions: Prostate Cancer
• Interventions: Biological: Sipuleucel-T without Booster; Biological: Sipuleucel-T with Booster

• Registration Number: NCT00715104
• Lead Sponsor: Dendreon

Brief Summary

This is an open label, Phase 2 trial of immunotherapy with sipuleucel-T as neoadjuvant treatment in men with localized prostate cancer.

Detailed Description

This is a single center, open label, Phase 2 study. Subjects will be treated with 3 infusions of sipuleucel-T prior to a scheduled radical prostatectomy (RP) surgery. To assess the immune response following treatment with sipuleucel-T, tissue from the prostatectomy specimen will be compared with tissue from the core biopsy specimen obtained prior to treatment with sipuleucel T. Following RP, subjects will be randomized to receive either a booster infusion of sipuleucel T or no further treatment with sipuleucel-T (i.e., booster: no booster).

Study Timeline

• Study Start: 2008-07
• Study First Submitted: 2008-07-11
• Study First Submitted QC: 2008-07-14
• Study First Posted: 2008-07-15
• Primary Completion: 2012-12
• Study Completion: 2013-12
• Results First Submitted: 2015-02-27
• Results First Submitted QC: 2015-03-17
• Status Verified: 2015-04
• Results First Posted: 2015-04-01
• Last Update Submitted: 2015-04-14
• Last Update Posted: 2015-05-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 42

Inclusion Criteria

• Adenocarcinoma of the prostate.
• Subject is scheduled for RP as the initial therapy for localized prostate cancer.
• Subject is ≥ 18 years of age.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Subject has adequate hematologic, renal, and liver function.

Exclusion Criteria

• Subject has any evidence of metastasis.
• Subject received hormones, including luteinizing hormone-releasing hormone agonists, antiandrogens, or 5 α-reductase inhibitors at any time prior to study screening.
• Subject has received prior radiation therapy or chemotherapy for prostate cancer.
• Subject has received systemic steroid therapy within 14 days.
• Subject has a history of stage III or greater cancer, excluding prostate cancer.
• Subjects with a history of basal or squamous cell skin cancers are allowed, provided that the subject was adequately treated and is disease-free at the time of study screening.
• Subjects with a history of stage I or II cancer must have been adequately treated and been disease-free for ≥ 3 years prior to study screening.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sipuleucel-T without Booster	Sipuleucel-T without Booster	Subjects were to receive 3 infusions of sipuleucel-T 12 weeks prior to RP, with no further sipuleucel-T treatment.
Sipuleucel-T with Booster	Sipuleucel-T with Booster	Subjects were to receive 3 infusions of sipuleucel-T 12 weeks prior to RP, and then an additional booster infusion 13 weeks following RP.

Primary Outcome Measures

Name	Time	Method
Change in the Number of Infiltrating CD3+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject	Pre-treatment biopsy (baseline) and post-RP (12 weeks post-treatment)	CD3+ T cell infiltration within prostate tissue was quantified using immunohistochemistry (IHC) staining techniques. Cells were enumerated per unit area (cells/μm2). For post-RP tissue specimens, three areas of interest were identified: Benign tissue, tumor tissue, and tumor interface tissue.

Secondary Outcome Measures

Name	Time	Method
Change in the Number of Infiltrating CD4+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject	Pre-treatment biopsy (baseline) and post-RP (12 weeks post-treatment)	CD4+ T cell infiltration within prostate tissue was quantified using immunohistochemistry (IHC) staining techniques. Cells were enumerated per unit area (cells/μm2). For post-RP tissue specimens, three areas of interest were identified: Benign tissue, tumor tissue, and tumor interface tissue.
Change in Antigen PA2024-specific T Cell Immunity in Peripheral Blood	Baseline (screening visit) and up to 12-weeks post-RP visit (24 weeks following sipuleucel-T)	Antigen PA2024-specific T cell immune response is measured using interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays.; This analysis was performed as previously described in Fong L et al. (J Immunol. 2001;167(12):7150-7156.). The unit of analysis is the number of IFN-γ ELISPOT counts per 300,000 peripheral blood mononuclear cells.
Change in Antigen PAP-specific T Cell Immunity in Peripheral Blood	Baseline (screening visit) and up to 12-weeks post-RP visit (24 months post sipuleucel-T)	Antigen PAP-specific T cell immune response is measured using interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays. PAP = Prostatic Acid Phosphatase.
Change in the Number of Infiltrating CD8+ T Cells Within the Prostate Tissue Between the Biopsy and the Post-RP Tissue Specimens in Each Subject	Pre-treatment biopsy (baseline) and post-RP (12 weeks following sipuleucel-T)	CD8+ T cell infiltration within prostate tissue was quantified using immunohistochemistry (IHC) staining techniques. Cells were enumerated per unit area (cells/μm2). For post-RP tissue specimens, three areas of interest were identified: Benign tissue, tumor tissue, and tumor interface tissue.
Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PA2024-Specific T Cell Immunity in the Peripheral Blood.	12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP	The number of PA2024-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells).
Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PAP-Specific T Cell Immunity in the Peripheral Blood.	12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP	The number of PAP-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells). PAP = Prostatic Acid Phosphatase.
Comparison of Booster Effect in Antigen PA2024-Specific T Cell Immunity Over Time Between the Two Randomized Groups	12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP	The number of Antigen PA2024-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells). The two groups were compared in the statistical model are: Randomized to Booster and Randomized to No Booster.
Comparison of Booster Effect in Antigen PAP-Specific T Cell Immunity Over Time Between the Two Randomized Groups	12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP	The number of Antigen PAP-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells). The two groups were compared in the statistical model are: Randomized to Booster and Randomized to No Booster. PAP = Prostatic Acid Phosphatase.

Trial Locations

Locations (7)

UCSF Comprehensive Cancer Center; 🇺🇸 San Francisco, California, United States

USC / Norris Comprehensive Cancer Center; 🇺🇸 Los Angeles, California, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Kaiser Permanente Portland; 🇺🇸 Portland, Oregon, United States

University of Utah School of Medicine; 🇺🇸 Salt Lake City, Utah, United States

Virginia Mason Medical Center; 🇺🇸 Seattle, Washington, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States