This is a prospective, randomized, open-label, phase II trial of cabozantinib in subjects with untreated, high risk prostate cancer undergoing radical prostatectomy. This multicenter study will enroll 30 subjects. Duke is the lead site for this trial. There will be a second site selected TBD. Patients will be assigned (first 9 subjects only) or randomized 2:1 to either: (1) cabozantinib 40 mg by mouth daily for 4 weeks, followed by a 2 week drug washout period before prostatectomy (n = 20), or (2) immediate prostatectomy within 12 weeks of registration (n = 10). The first 9 subjects (6 subjects assigned to cabozantinib treatment, 3 subjects assigned to immediate prostatectomy) will constitute the Safety Lead-In Cohort, which will be only accrued at Duke. After six subjects have received cabozantinib and completed the 57-85 day safety visit without triggering a stopping rule, subjects may be accrued at the ex-Duke site. The primary goal is to compare pathologic apoptotic indices (cleaved caspase-3) in prostatectomy specimens from patients who undergo immediate prostatectomy (controls) versus those who receive with cabozantinib followed by prostatectomy. The secondary objective is to conduct immune phenotypic profiling on the peripheral blood and tumor microenvironment in prostatectomy specimens from both groups. A statistical analysis will be used to compare the apoptotic indices between the two groups.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
3
Cabozantinib 40 mg by mouth daily for 4 weeks.
Radical prostatectomy as part of routine medical care.
Duke University Medical Center
Durham, North Carolina, United States
Apoptotic Index in Prostatectomy Specimens From Patients Who Undergo Immediate Prostatectomy (Arm B) Versus Those Treated With Cabozantinib Followed by Prostatectomy (Arm A)
Apoptotic index as measured by cleaved caspase-3 levels in tumor tissue
Time frame: At prostatectomy (Arm A: Day 43, Arm B: Day 1)
Immune Phenotyping of Myeloid-derived Suppressor Cells (MDSCs)
Percentage of MDSCs in peripheral blood and tumor tissue
Time frame: Arm A: Screening, Day 29, Day 43, Day 57-85; Arm B: Screening, Day 1
Immune Phenotyping of Neutrophils
Percentage of neutrophils in peripheral blood and tumor tissue
Time frame: Arm A: Screening, Day 29, Day 43, Day 57-85; Arm B: Screening, Day 1
Immune Phenotyping of M1 Macrophages
Percentage of M1 macrophages in peripheral blood and tumor tissue
Time frame: Arm A: Screening, Day 29, Day 43, Day 57-85; Arm B: Screening, Day 1
Immune Phenotyping of M2 Macrophages
Percentage of M2 macrophages in peripheral blood and tumor tissue
Time frame: Arm A: Screening, Day 29, Day 43, Day 57-85; Arm B: Screening, Day 1
Immunohistochemical (IHC) Analysis of CD8+
Percentage of CD8+ positive cells in tumor tissue
Time frame: At prostatectomy (Arm A: Day 43, Arm B: Day 1)
Immunohistochemical (IHC) Analysis of Programmed Death Ligand-1 (PD-L1)
Percentage of PD-L1 positive cells in tumor tissue
Time frame: At prostatectomy (Arm A: Day 43, Arm B: Day 1)
Immunohistochemical (IHC) Analysis of Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4)
Percentage of CTLA-4 positive cells in tumor tissue
Time frame: At prostatectomy (Arm A: Day 43, Arm B: Day 1)
Immunohistochemical (IHC) Analysis of Interleukin-1 Receptor Antagonist (IL-1RA)
Percentage of IL-1RA positive cells in tumor tissue
Time frame: At prostatectomy (Arm A: Day 43, Arm B: Day 1)
Description of the Neutrophil Chemotactic Factor CXCL12
Percentage of neutrophil chemotactic factor CXCL12 positive cells in tumor tissue
Time frame: At prostatectomy (Arm A: Day 43, Arm B: Day 1)
Description of the Neutrophil Chemotactic Factor HMGB1
Percentage of neutrophil chemotactic factor HMGB1 positive cells in tumor tissue
Time frame: At prostatectomy (Arm A: Day 43, Arm B: Day 1)
Description of the MDSC-promoting Cytokine CCL5
Percentage of MDSC-promoting cytokine CCL5 positive cells in tumor tissue
Time frame: At prostatectomy (Arm A: Day 43, Arm B: Day 1)
Description of the MDSC-promoting Cytokine CCL12
Percentage of MDSC-promoting cytokine CCL12 positive cells in tumor tissue
Time frame: At prostatectomy (Arm A: Day 43, Arm B: Day 1)
Description of the MDSC-promoting Cytokine CD40
Percentage of MDSC-promoting cytokine CD40 cells in tumor tissue
Time frame: At prostatectomy (Arm A: Day 43, Arm B: Day 1)
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