Brief Summary
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.
Brief Title
Sequencing of Sipuleucel-T and ADT in Men With Non-metastatic Prostate Cancer
Detailed Description
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.
• 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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Prostatic Neoplasm
Prostate Cancer
Prostatic Adenocarcinoma
Eligibility Criteria
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.
* 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.
Inclusion Criteria
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
* 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
Gender
Male
Gender Based
false
Keywords
Immune therapy
Cancer vaccine
Therapeutic vaccine
Therapeutic cancer vaccine
Vaccine
Dendritic cells
PSA
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)
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01431391
Org Class
Industry
Org Full Name
Dendreon
Org Study Id
P10-2
Overall Status
Completed
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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
Primary Outcomes
Outcome Description
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.
Outcome Measure
Immune Response at Month 24 as Evaluated by IFN-γ ELISPOT Specific for PA2024
Outcome Time Frame
PA2024 ELISPOT counts at Month 24
Secondary Outcomes
Outcome Description
A participant was considered to have an immune response it the post-baseline PA2024-specific IFN-g ELISPOT count was \>18
Outcome Time Frame
Month 24
Outcome Measure
Percentage of Participants With Immune Response As Evaluated by IFN-γ ELISPOT Specific for PA2024
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Sanjay Goel
Investigator Email
sgoel@montefiore.org
Investigator Phone
718-405-8404