Background: Prostate cancer is the second most common cause of cancer-related death among men in the United States. Early-stage, low-grade prostate cancer is managed with active monitoring. However, 35% of men with this cancer will need treatment within 5 years because of tumor growth. Researchers want to know if a new vaccine that targets 3 anti-cancer proteins (TriAdeno) plus a drug (N-803) approved for bladder cancer can help stop prostate tumors from growing. Objective: To test TriAdeno and N-803 in people with early-stage prostate cancer. Eligibility: People aged 18 years and older with early-stage low- or medium-risk prostate cancer. Design: Participants will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. They will have an imaging scan. They may have a rectal exam. TriAdeno is injected under the skin of the upper thigh; N-803 is injected under the skin of the abdomen. Participants will be treated in up to four 21-day cycles. They will get both injections on the first day of each cycle. Participants may opt to complete a memory aid: They may record all of their symptoms for 7 days after each injection. They may also complete a questionnaire about their prostate symptoms. Blood tests, imaging scans, and other tests will be repeated during the study. A tissue sample (biopsy) of the tumor will be collected during or after cycle 2; a second biopsy may be taken about 1 year later. Participants will have follow-up phone calls for 5 years....
Background: * Prostate cancer (PCa) is the most common non-cutaneous cancer and second most common cause of cancer-related death among men living in the United States. * With increasing detection of localized, low-grade PCa in the prostate-specific antigen (PSA) screening era, active surveillance of PCa has emerged as a viable management strategy in selected, favorable risk population. Though active surveillance is the preferred management strategy for low-grade PCa and an option for selected favorable, intermediate risk disease according to the National Comprehensive Cancer Network (NCCN), up to 35 percent of men will need radical therapy within 5 years due to progression of PCa. * Vaccine strategies represent a novel therapeutic approach in the prevention and possible treatment of early-stage PCa. A new trivalent vaccine which targets 3 tumor associated antigens (PSA, brachyury, and MUC-1) has been shown to induce an immune response in a Phase I study of patients with metastatic castrate-resistant PCa. * N-803 is an IL-15 agonist that activates and expands T cells and NK cells. N-803 enhances anti-tumor activity in combination with tumor-targeted vaccines. Clinically, multiple studies have demonstrated the safety of tumor-targeted vaccine in combination with PD-1/PD-L1 blockade. Adding N-803 to PD-1/PD-L1 blockade can produce antitumor responses in disease states where responses to PD-1/PD-L1 alone would not be expected. * The TriAdeno vaccine has not been evaluated in populations with early stage, low grade PCa. Primary Objective: -To determine the effect of an Ad5 PSA/MUC-1/brachyury-based immunotherapy vaccine (TriAdeno) with IL-15 superagonist N-803 on immune infiltration of the local tumor environment by comparing pre- and post-treatment CD8+ and CD4+ T-cell density within the malignant portion of prostate biopsies in participants on active surveillance for low and intermediate risk prostate cancer Eligibility: * Biopsy-proven, organ confined low or intermediate risk adenocarcinoma of the prostate * Age \>=18 years * Serum PSA \<20 ng/mL (or \<10 ng/mL for participants being treated with 5-alpha reductase inhibitors) * Eastern Cooperative Oncology Group (ECOG) performance status \<=1 Design: * This is an open-label, non-randomized Phase II trial of TriAdeno vaccine given concurrently with N-803 in participants with localized, early stage, low and intermediate risk PCa on active surveillance. * The TriAdeno vaccines will be administered subcutaneously (SC) at doses of 5x1011 viral particles (VP) on Day 1 of every 21-day cycle for up to four (4) cycles. * N-803 will be administered SC at 15 mcg/kg on Day 1 of every 21-day cycle for up to four (4) cycles. * Up to 49 participants may be treated.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
52
The TriAdeno vaccine will be administered on Day 1 of every 21-day cycle for up to 4 cycles.
N-803 will be administered on Day 1 of every 21-day cycle for up to 4 cycles.
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
To determine the effect of TriAdeno vaccine with N-803 on immune infiltration of the local tumor environment
Change in the density of T-cell immune infiltrates in the malignant portions of prostate using a paired two sample t-test
Time frame: Baseline/prior to treatment, C2D14 (or as late as C4D21), and optionally at 1 year
To assess the adverse events associated with TriAdeno vaccine and N-803
Toxicities will be reported in a descriptive fashion per type, frequency, and grade
Time frame: Day 1 of each cycle, and through at least 30 days after last treatment
To determine the effect of the TriAdeno vaccines with N-803 on the change in PSA
Change in PSA will be analyzed using a paired two sample t-test.
Time frame: Day 1 of each cycle after C1, 30 days after last treatment, and in follow-up about every 3 months for 1 year and every 6 months for the subsequent 4 years after the end of study therapy
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