Functional Microscale Organotypic Assays to Predict Patient Response to Anti-Angiogenesis Therapies
Trial Snapshot
- Phase
- Phase 2
- Status
- Terminated
- Enrollment
- 5
- Locations
- 1
- Primary Endpoint
- Baseline Tumor FDG PET SUV Data by Disease Type at Baseline
Study Overview
Brief Summary
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).
Detailed Description
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 Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients diagnosed with locally advanced (>/=cT3) or metastatic clear cell RCC as proven by biopsy.
- •Adults, 18 years of age or older.
- •Surgical candidates who have clinical indication for nephrectomy and standard-of-care biopsy of metastatic disease followed by possible standard of care systemic anti-angiogenesis based treatment regimen
- •Have consented to participate in the University of Wisconsin Carbone Cancer Center Biobank.
Exclusion Criteria
- •Patients who have received prior RCC systemic therapies
- •Prior history of prostate cancer
- •Prior history of any other malignancy within the last 2 years, other than skin basal cell or cutaneous superficial squamous cell carcinoma that has not metastasized and superficial bladder cancer
- •Unable to lie flat during or tolerate PET/CT
- •Serum creatinine > 2 times the upper limit of normal
Arms & Interventions
18F-DCFPyL whole body PET/CT scan
18F-DCFPyL whole body PET/CT scan at three time-points
Intervention: PSMA-based 18F-DCFPyL PET tracer for PET/CT exams (Drug)
Outcomes
Primary Outcomes
Baseline Tumor FDG PET SUV Data by Disease Type at Baseline
Time Frame: 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)
Histopathological Endpoints: Immunohistochemical Staining for PSMA
Time Frame: Up to 24 months
Compare PSMA imaging to histopathological endpoints which include tumor vascular density, immunohistochemical staining for PSMA and neovascularization (CD105, CD31 markers)
Histopathological Endpoints: Tumor Vascular Density
Time Frame: Up to 24 months
Compare PSMA imaging to histopathological endpoints which include tumor vascular density, immunohistochemical staining for PSMA and neovascularization (CD105, CD31 markers)
Histopathological Endpoints: Neovascularization Measured by CD105 and CD31 Markers
Time Frame: Up to 24 months
Compare PSMA imaging to histopathological endpoints which include tumor vascular density, immunohistochemical staining for PSMA and neovascularization (CD105, CD31 markers)
Secondary Outcomes
- Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Vessel Sprouting(Up to 24 months)
- Evaluate the Predictive Power and Validate the uVESSEL Model(Up to 24 months)
- Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): PMSA Expression(Up to 24 months)
- Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Cell Death(Up to 24 months)