Sequencing of Sipuleucel-T and ADT in Men With Non-metastatic Prostate Cancer

Study Overview
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Brief Summary
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The main purpose of this study was to determine whether ADT started before or after sipuleucel-T led to a better immune system response. This study also evaluated the safety of sipuleucel-T and ADT treatment, immune system responses over time, the characteristics of sipuleucel-T, and changes in prostate specific antigen (PSA) values over time.

Detailed Description
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Multicenter, randomized, open-label study, with subjects allocated (1:1) to 1 of 2 study arms, using a stratified randomization based on: • Prostate-specific antigen doubling time (PSADT): ≤ 3 months or > 3 months and ≤ 12 months. • Primary therapy: radical prostatectomy (RP) or radiation, including brachytherapy, (XRT) or RP + XRT. Arm 1: Subjects received one infusion of sipuleucel-T every two weeks for a total of three infusions. Two weeks after the third sipuleucel-T infusion, subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg). An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT. Arm 2: Subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg) 12 weeks before infusion 1 of sipuleucel-T. An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT. Twelve weeks after the initial leuprolide 45 mg depot injection, subjects began one infusion of sipuleucel-T every two weeks for a total of three infusions. Cellular and humoral immune responses were assessed for Arm 2 subjects at 12, 8, and 4 weeks pre infusion 1, and in all subjects (both arms) at pre-leukapheresis 1, 2, and 3, and post-infusion 1, 2 and 3, and at the following time points after the third infusion: Weeks 2, 6, and 12 and Months 6, 9, 12, 15, 18, 21, and 24. Safety assessments included adverse event (AE) monitoring, laboratory tests (complete blood count (CBC) and serum chemistry), vital signs, Eastern Cooperative Oncology Group (ECOG) performance status, physical examination, as well PSA and testosterone monitoring. The study was complete at the 27-Month visit for Arm 1 and the 24-Month visit for Arm 2.

Official Title
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A Randomized, Open-Label, Phase 2 Trial Examining the Sequencing of Sipuleucel-T and Androgen Deprivation Therapy in Men With Non-metastatic Prostate Cancer and a Rising Serum Prostate Specific Antigen After Primary Therapy

Conditions
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Prostatic Neoplasm, Prostate Cancer, Prostatic Adenocarcinoma

Intervention / Treatment
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* Biological: sipuleucel-T
* Drug: leuprolide acetate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hormone-sensitive prostate cancer Non-metastatic disease, as evidenced by negative bone scan or computed tomography of the abdomen and pelvis ECOG performance status ≤ 1 Histologically documented prostate cancer Prior primary therapy for prostate cancer Rising PSA with a PSADT of ≤ 12 months Testosterone ≥ 200 ng/dL ≤ 28 days of registration Adequate hematologic, renal, and liver function Must live in a permanent residence within a comfortable driving distance (round-trip within one day) to the clinical research site Exclusion Criteria: Requires systemic ongoing immunosuppressive therapy History of allergic reactions attributed to compounds of similar chemical or biologic composition to sipuleucel-T or GM-CSF Prior sipuleucel-T therapy Prior ADT therapy ≤ 6 months prior to registration or ≥ 6 months duration in total If subject has a history of any other stage III/IV malignancy, the subject must be disease free and off any malignancy-related treatment for at least 10 years. If the subject has a history of any stage I-II malignancy, the subject must be disease free and off any malignancy-related treatment for at least 5 years. Prior experimental immunotherapy or on an experimental clinical trial within 1 year Received denosumab or XRT ≤ 6 months prior to registration Received chemotherapy or GM-CSF ≤ 90 days prior to registration Received any of the following medications or interventions ≤ 28 days prior to registration major surgery requiring general anesthesia systemic immunosuppressive therapy other prescription treatment for prostate cancer Active infection within 1 week of registration Likely to receive XRT or surgery for prostate cancer during the study period Any medical intervention, any other condition, or any circumstances that could compromise the study.

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: Arm 1: Sipuleucel-T followed by ADT<br>Arm 1: Subjects received one infusion of sipuleucel-T every two weeks for a total of three infusions. Two weeks after the third sipuleucel-T infusion, subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg). An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT. | Biological: sipuleucel-T<br>* Sipuleucel-T is an autologous cellular product consisting of antigen presenting cells (APCs) activated with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).<br>* Other names: APC8015;Drug: leuprolide acetate<br>* 45.0 mg depot injection, 2 doses 6 months apart<br>* Other names: Eligard®;|
| Experimental: Arm 2: ADT followed by sipuleucel-T<br>Arm 2: Subjects started ADT with 45 mg leuprolide acetate depot injection (Eligard® 45 mg) 12 weeks before infusion 1 of sipuleucel-T. An additional leuprolide acetate injection was administered at 6 months after the first injection for a total of 2 injections and 12 months of ADT. Twelve weeks after the initial leuprolide 45 mg depot injection, subjects began one infusion of sipuleucel-T every two weeks for a total of three infusions. | Biological: sipuleucel-T<br>* Sipuleucel-T is an autologous cellular product consisting of antigen presenting cells (APCs) activated with PA2024, a recombinant fusion protein composed of prostatic acid phosphatase (PAP), linked to granulocyte-macrophage colony-stimulating factor (GM-CSF).<br>* Other names: APC8015;Drug: leuprolide acetate<br>* 45.0 mg depot injection, 2 doses 6 months apart<br>* Other names: Eligard®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune Response at Month 24 as Evaluated by IFN-γ ELISPOT Specific for PA2024 | Immune response at month 24 as evaluated by IFN-γ ELISPOT specific for PA2024 following sipuleucel-T/ADT treatment regimens to determine if order of administration impacted immune response. | PA2024 ELISPOT counts at Month 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Immune Response As Evaluated by IFN-γ ELISPOT Specific for PA2024 | A participant was considered to have an immune response it the post-baseline PA2024-specific IFN-g ELISPOT count was >18 | Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSA, Immune therapy, Cancer vaccine, Therapeutic vaccine, Therapeutic cancer vaccine, Vaccine, Dendritic cells, Androgen deprivation therapy, Prostatic Neoplasms, Genital Neoplasms, Male, Urogenital Neoplasms, Neoplasms, Prostatic Diseases, Androgens, Hormones, Adenocarcinoma, Carcinoma, Neoplasms, Glandular and Epithelial, Immunology, Hormone therapy, Immunotherapy, Luteinizing hormone-releasing hormone (LHRH)