The primary objective of this research is to evaluate response to systemic therapy, including anti-angiogenesis therapy and/or immune-based therapies via 18F-DCFPyL prostate-specific membrane antigen (PSMA)-based positron emission tomography/computed tomography (PET/CT) in patients with metastatic renal cell carcinoma (RCC) and to compare qualitatively with conventional imaging response criteria - Response Evaluation Criteria In Solid Tumors (RECIST 1.1) and histopathological endpoints including isolation, enumeration and staining of Circulating Tumor Cells (CTC).
Response of systemic therapy, including anti-angiogenesis therapy and/or immune-based therapies will be quantified using PSMA-based PET imaging using a novel agent,18F-DCFPyL, as a non-invasive imaging biomarker of tumor neovasculature to functionally monitor renal cell cancer neovasculature in patients undergoing systemic anti-angiogenesis therapy. PSMA PET will be compared with response to anti-angiogenesis therapy using conventional imaging computed tomography(CT)-based RECIST1.1 criteria as well as histopathological endpoints (tumor vascular density, immunohistochemical staining for PSMA and neovascularization (cluster of differentiation(CD)105, CD31). Whole body PSMA PET/CT scans will be obtained at baseline, following adjuvant anti- angiogenic therapy and when the patient becomes refractory to treatment. The rationale and time points for obtaining PET scans is planned with respect to the typical natural history of metastatic RCC. This project will obtain information from tumors that are responding to anti-angiogenesis therapy and those resistant to treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
5
18F-DCFPyL whole body PET/CT scan administered at the following timepoints: PET1 - Prior to scheduled nephrectomy PET2 - to establish a new baseline PET before systemic therapy * PET2A - Post-surgery and prior to start of standard of care systemic therapy * PET2B - 12-16 weeks from start of first line systemic therapy (immune-based or anti-angiogenic) PET3 - If first line systemic therapy did not include anti-angiogenesis therapy and new systemic therapy does include anti-angiogenesis therapy * PET3A - Prior to start of additional anti-angiogenesis therapy * PET3B - 12-16 weeks from the start of additional anti-angiogenesis therapy PET4 - obtained at clinical progression or 2 years following initial systemic therapy
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, United States
Baseline Tumor FDG PET SUV Data by Disease Type at Baseline
Tumor FDG PET SUV data is provided from baseline PET tumor data. Participants with baseline 18F-DCFPyL PSMA PET/CT prior to surgical nephrectomy and metastatic disease sampling were analyzed based single timepoints for PET SUVmax values of tumor uptake (primary and metastatic disease)
Time frame: Baseline
Histopathological Endpoints: Immunohistochemical Staining for PSMA
Compare PSMA imaging to histopathological endpoints which include tumor vascular density, immunohistochemical staining for PSMA and neovascularization (CD105, CD31 markers)
Time frame: Up to 24 months
Histopathological Endpoints: Tumor Vascular Density
Compare PSMA imaging to histopathological endpoints which include tumor vascular density, immunohistochemical staining for PSMA and neovascularization (CD105, CD31 markers)
Time frame: Up to 24 months
Histopathological Endpoints: Neovascularization Measured by CD105 and CD31 Markers
Compare PSMA imaging to histopathological endpoints which include tumor vascular density, immunohistochemical staining for PSMA and neovascularization (CD105, CD31 markers)
Time frame: Up to 24 months
Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Vessel Sprouting
Patient-derived uVESSEL models (from primary \& metastatic sites) and incorporating patient-derived immune cells, will be tested for response to anti-angiogenic therapies including pazopanib, sunitinib, cabozantinib, and axitinib. Response will be quantified via multiple endpoints, e.g. vessel sprouting, PSMA expression, cell death.
Time frame: Up to 24 months
Evaluate the Predictive Power and Validate the uVESSEL Model
Using the clinical, pathological and imaging endpoints, predictive models will e developed using responses to uVESSEL model above. More specifically the objective response (dichotomous endpoint of yes or no) measured using PSMA-based PET/CT will be used as a dependent variable in a logistic regression model with response to uVESSEL model from above as an independent predictor to segregate uVESSEL responses into two groups corresponding to responders and non-responders to anti-angiogenic therapies.
Time frame: Up to 24 months
Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): PMSA Expression
Patient-derived uVESSEL models (from primary \& metastatic sites) and incorporating patient-derived immune cells, will be tested for response to anti-angiogenic therapies including pazopanib, sunitinib, cabozantinib, and axitinib. Response will be quantified via multiple endpoints, e.g. vessel sprouting, PSMA expression, cell death.
Time frame: Up to 24 months
Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Cell Death
Patient-derived uVESSEL models (from primary \& metastatic sites) and incorporating patient-derived immune cells, will be tested for response to anti-angiogenic therapies including pazopanib, sunitinib, cabozantinib, and axitinib. Response will be quantified via multiple endpoints, e.g. vessel sprouting, PSMA expression, cell death. Two subjects had data collected and were assessed.
Time frame: Up to 24 months
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