Sipuleucel-T as Neoadjuvant Treatment in Prostate Cancer

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

Detailed Description
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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).

Official Title
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An Open Label, Phase 2 Trial of Immunotherapy With Sipuleucel-T (Provenge®) as Neoadjuvant Treatment in Men With Localized Prostate Cancer

Conditions
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Prostate Cancer

Intervention / Treatment
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* Biological: Sipuleucel-T with Booster
* Biological: Sipuleucel-T without Booster


Participation Criteria
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Eligibility Criteria
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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.

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

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sipuleucel-T with Booster<br>Subjects were to receive 3 infusions of sipuleucel-T 12 weeks prior to RP, and then an additional booster infusion 13 weeks following RP. | Biological: Sipuleucel-T with Booster<br>* Sipuleucel-T is an autologous active cellular immunotherapy product designed to stimulate an immune response against prostate cancer. Sipuleucel-T consists of autologous peripheral blood mononuclear cells (PBMCs), including antigen presenting cells (APCs), that have been activated in vitro with a recombinant fusion protein.<br>|
| Experimental: Sipuleucel-T without Booster<br>Subjects were to receive 3 infusions of sipuleucel-T 12 weeks prior to RP, with no further sipuleucel-T treatment. | Biological: Sipuleucel-T without Booster<br>* Sipuleucel-T is an autologous active cellular immunotherapy product designed to stimulate an immune response against prostate cancer. Sipuleucel-T consists of autologous peripheral blood mononuclear cells (PBMCs), including antigen presenting cells (APCs), that have been activated in vitro with a recombinant fusion protein.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Pre-treatment biopsy (baseline) and post-RP (12 weeks post-treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 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. | Pre-treatment biopsy (baseline) and post-RP (12 weeks post-treatment) | 
| 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 | 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. | Pre-treatment biopsy (baseline) and post-RP (12 weeks following sipuleucel-T) | 
| Change in Antigen PA2024-specific T Cell Immunity in Peripheral Blood | 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. | Baseline (screening visit) and up to 12-weeks post-RP visit (24 weeks following sipuleucel-T) | 
| Change in Antigen PAP-specific T Cell Immunity in Peripheral Blood | Antigen PAP-specific T cell immune response is measured using interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays. PAP = Prostatic Acid Phosphatase. | Baseline (screening visit) and up to 12-weeks post-RP visit (24 months post sipuleucel-T) | 
| Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PA2024-Specific T Cell Immunity in the Peripheral Blood. | The number of PA2024-specific T cells was enumerated by interferon gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assays (memory T cells). | 12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP | 
| Effect of a Post-RP Booster Infusion of Sipuleucel-T Over Time of Antigen PAP-Specific T Cell Immunity in the Peripheral Blood. | 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. | 12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP | 
| Comparison of Booster Effect in Antigen PA2024-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 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. | 12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP | 
| Comparison of Booster Effect in Antigen PAP-Specific T Cell Immunity Over Time Between the Two Randomized Groups | 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. | 12 Weeks Post-RP (Pre-booster) and up to 72 Weeks post-RP |