Imaging Studies of Kidney Cancer Using 18F-VM4-037

Phase 2

Terminated

Conditions: Carcinoma, Renal Cell
Kidney Neoplasms

Interventions: Drug: 18F-VM4-037
Procedure: PET/CT

Registration Number: NCT01712685

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: Background:

- The drug 18F-VM4-037 is being tested for use in cancer imaging studies. It may help tumor tissue show up more clearly during scans. Researchers want to see how well it works for scans for people who have kidney cancer.

Objectives:

- To test the safety and effectiveness of 18F-VM4-037 during imaging studies of kidney cancer.

Eligibility:

- Adults at least 18 years of age with kidney cancer that will be treated with surgery.

Design:

* Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected.

* Participants will have two positron emission tomography (PET) scans of their kidneys. They will have the scans before and after receiving an injection of 18F-VM4-037. The scans will take about 2 hours to complete.

* About 3 weeks after the PET scans, participants will provide tumor tissue samples from their kidneys.

* This is a scanning study only. Treatment will not be provided as part of this study.

Detailed Description: BACKGROUND:

* Carbonic Anhydrase IX (CA IX) is a hypoxia-inducible enzyme regulated by the Von Hippel Lindau (VHL) protein that is commonly overexpressed in certain malignancies including renal cell carcinoma (RCC) and may have prognostic significance.

* The VHL gene is commonly mutated or inactivated in RCC tumors and VHL activity regulated the expression and activity of not only CAIX but also CAXII as well as other genes critical for tumor angiogenesis such as vascular endothelial growth factor (VEGF), glucose transporter 1 (GLUT1), glucose transporter 3 (GLUT 3) and platelet derived growth factor (PDGF).

* 18F-VM4-037 is an imaging drug product formulation which binds to the active site ligand of CA-IX and also binds to CAXII. We propose to evaluate 18F-VM4-037 as a positron emission imaging (PET) radiopharmaceutical for the in vivo detection of CA-IX and CAXII in renal tumors.

STUDY OBJECTIVES

PRIMARY OBJECTIVE:

* To evaluate the biodistribution of 18F-VM4-037 within tumor and non-tumor tissues.

* To assess safety of 18F-VM4-037 in patients with primary or metastatic RCC.

ELIGIBILITY:

* Subject is greater than or equal to 18 years old, Eastern Cooperative Oncology Group (ECOG) 0-2.

* Subject must have confirmed primary RCC (greater than or equal to 2.5cm) in diameter on conventional imaging modality or extrarenal/extrahepatic RCC lesion (greater than or equal to 1cm).

DESIGN:

- Twenty subjects with primary RCC greater than or equal to 2.5cm in diameter or extrarenal/extrahepatic lesion suspicious for metastatic RCC (greater than or equal to 1cm in diameter) scheduled for clinically indicated surgery or biopsy will undergo dynamic 18F-VM4-037 PET/CT imaging. Results will be compared with pathology.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 12

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Renal Cell Carcinoma	18F-VM4-037	-
Renal Cell Carcinoma	PET/CT	-

Primary Outcome Measures

Name	Time	Method
Level of Uptake of 18F-VM4-037 in Tumor and Non Tumor Tissues, Calculated as Standardized Uptake Values (SUVs)	58 days	The primary outcome measure will be assessed from quantitative measurements (e.g., correlate immunohistochemistry (IHC) results with standardized uptake values (SUVs) from positron emission tomography (PET) images) of the level of uptake of tumor and non tumor tissues into each target lesion, calculated as standardized uptake values. Normal renal parenchyma and muscle are both "non-tumor" tissue.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	58 days	Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
Mean Standard Uptake Value (SUV) for All Target Lesions	Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.	Mean SUV for all target lesions was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).
Mean Standard Uptake Value (SUV) for Primary Clear Cell Renal Carcinoma (ccRCC)	Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.	Mean SUV for primary clear cell renal carcinoma was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).
Mean Standard Uptake Value (SUV) for Normal Kidney	Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.	Mean SUV for normal kidney was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).
Number of Participants With a Mutation of the Von Hippel-Lindau (VHL) Gene	21 days prior to enrollment until closure of the study, approximately 14 months.	Germline VHL mutation testing was performed using Clinical Laboratory Improvement Amendments (CLIA) certified laboratories.
Distribution Volume Ratio (DVR) for the Primary Kidney Lesions	Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.	DVR of the lesions was measured by the Logan graphical analysis method.
Time to Peak Activity Derived From Time Activity Curve (TAC)	Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.	The time to peak activity of radiotracer (tumor marker) uptake indicates the optimal time to image to obtain best tumor visibility.
Kinetic (Ki) Rate Constant	Dynamic imaging was performed for the first 45 minutes post injection and whole body imaging was obtained at 60 minutes post injection. Tumors were surgically excised or biopsied within 4 weeks of imaging.	Ki was assessed by the Patlak graphical analysis method which measures the uptake rate constant Ki.