Clinical trial NCT03387514: Functional Microscale Organotypic Assays to Predict Patient Response to Anti-Angiogenesis Therapies
Official title: Functional Microscale Organotypic Assays to Predict Patient Response to Anti-Angiogenesis Therapies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Renal Cell Carcinoma
Keywords: Clear Cell
Kidney Cancer
RCC
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2018-01-02
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This study is a single cohort study without randomization or stratification.
Primary purpose: DIAGNOSTIC

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.

Eligibility criteria: 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

Primary outcomes:
measure: Baseline Tumor FDG PET SUV Data by Disease Type at Baseline
timeFrame: Baseline
measure: Histopathological Endpoints: Immunohistochemical Staining for PSMA
timeFrame: Up to 24 months
measure: Histopathological Endpoints: Tumor Vascular Density
timeFrame: Up to 24 months
measure: Histopathological Endpoints: Neovascularization Measured by CD105 and CD31 Markers
timeFrame: Up to 24 months
Secondary outcomes:
measure: Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Vessel Sprouting
timeFrame: Up to 24 months
measure: Evaluate the Predictive Power and Validate the uVESSEL Model
timeFrame: Up to 24 months
measure: Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): PMSA Expression
timeFrame: Up to 24 months
measure: Measure Therapy Response of Patient Specific uVESSEL (a Micro Scale Organotypic Co-culture Model): Cell Death
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Steve Cho, MD
role: PRINCIPAL_INVESTIGATOR
References: