Functional Microscale Organotypic Assays to Predict Patient Response to Anti-Angiogenesis Therapies

Renal Cell Carcinoma Clinical Trial

— UW17104  

Official title:

Functional Microscale Organotypic Assays to Predict Patient Response to Anti-Angiogenesis Therapies

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03387514
• Other study ID #: 2017-1343
• Secondary ID: P30CA014520A5393
• Status: Terminated
• Phase: Phase 2
• Start date: December 8, 2018
• Est. completion date: June 29, 2021

Study information

• Verified date: December 2022
• Source: University of Wisconsin, Madison
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: June 29, 2021
• Est. primary completion date: June 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Renal Cell
• Renal Cell Carcinoma

Intervention

Drug:
• PSMA-based 18F-DCFPyL PET tracer for PET/CT exams
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

Locations

Country	Name	City	State
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin

Sponsors (3)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Baseline
Primary	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)	Up to 24 months
Primary	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)	Up to 24 months
Primary	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)	Up to 24 months
Secondary	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.	Up to 24 months
Secondary	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.	Up to 24 months
Secondary	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.	Up to 24 months
Secondary	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.	Up to 24 months