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

PET Imaging Of Renal Cell Carcinoma With 18F-VM4-037: A Phase II Pilot Study For Detection Of Disease And Correlation With VHL Mutation Status

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.

Study Overview

• Status: Terminated
• Conditions: Kidney Neoplasms; Carcinoma, Renal Cell
• Intervention / Treatment: Drug: 18F-VM4-037; Procedure: PET/CT

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

• INCLUSION CRITERIA:
• Subject is greater than or equal to18 years old.
• Subject must be scheduled to undergo surgery or biopsy for primary renal cell carcinoma (RCC) greater than or equal to 2.5cm in diameter or extrarenal/extrahepatic metastatic RCC lesion (greater than or equal to1cm in diameter) at the National Institutes of Health (NIH) Clinical Center based on imaging within 3 weeks.
• Chemistry parameters: aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 2 times of the upper limits of normal; total bilirubin, of < 2 times the upper limits of normal or < 3.0 mg/dl in patients with Gilberts syndrome.
• Eastern Cooperative Oncology Group (ECOG) Performance score of 0 to 2.
• Ability to provide informed consent. All subjects must sign an informed consent form indicating their understanding of the investigational nature and risks of the study before any protocol-related studies are performed.
• The subject has a clinically acceptable medical history, physical examination and vital signs findings during the screening period (from within 21 days before administration of 18F-VM4-037). Components of an acceptable medical history include no active infection at the time of enrollment or within 7 days of enrollment, no prior therapy that results in immunocompromise or impaired renal function (serum creatinine within 2 weeks prior to positron emission tomography (PET) imaging less than or equal to1.8 mg/dl and epidermal growth factor receptor (eGFR) must be > 30 ml/min/1.73m^2) or findings indicating an inability to tolerate the requirements for the scan. Previous exposure to immunocompromising therapy does not exclude the patient; patients must have an absolute neutrophil count > 1.5/microL within 2 weeks of PET imaging.
• If female, must have a negative serum human chorionic gonadotropin (HCG) within 24 hours prior to 18F-VM4-037 injection OR be post menopausal for > 2 years OR be surgically sterile.

EXCLUSION CRITERIA:

• Subjects for whom participating would significantly delay the scheduled standard of care therapy.
• Subjects with any coexisting medical or psychiatric condition that is likely to interfere with study procedures and/or results.
• Subjects with severe claustrophobia unresponsive to oral anxiolytics.
• Other medical conditions deemed by the principle investigator (or associates) or sponsor to make the subject ineligible for protocol procedures.
• Female subject is pregnant or nursing
• The site of the target lesion must not have been part of a radiation portal within 6 months of enrollment.
• Subjects having received another investigational agent within 1 month before administration of 18F-VM4-037.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Renal Cell Carcinoma	Drug: 18F-VM4-037; Drug being tested for use in cancer imaging studies. It may help tumor tissue show up more clearly during scans.; Procedure: PET/CT; Other Names: Positron emission tomography; Computed tomography

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of Uptake of 18F-VM4-037 in Tumor and Non Tumor Tissues, Calculated as Standardized Uptake Values (SUVs)	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.	58 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Adverse Events	Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.	58 days
Mean Standard Uptake Value (SUV) for All Target Lesions	Mean SUV for all target lesions was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).	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 Standard Uptake Value (SUV) for Primary Clear Cell Renal Carcinoma (ccRCC)	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).	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 Standard Uptake Value (SUV) for Normal Kidney	Mean SUV for normal kidney was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).	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.
Number of Participants With a Mutation of the Von Hippel-Lindau (VHL) Gene	Germline VHL mutation testing was performed using Clinical Laboratory Improvement Amendments (CLIA) certified laboratories.	21 days prior to enrollment until closure of the study, approximately 14 months.
Distribution Volume Ratio (DVR) for the Primary Kidney Lesions	DVR of the lesions was measured by the Logan graphical analysis method.	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.
Time to Peak Activity Derived From Time Activity Curve (TAC)	The time to peak activity of radiotracer (tumor marker) uptake indicates the optimal time to image to obtain best tumor visibility.	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.
Kinetic (Ki) Rate Constant	Ki was assessed by the Patlak graphical analysis method which measures the uptake rate constant Ki.	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.

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Adam R Metwalli, M.D., National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Latif F, Tory K, Gnarra J, Yao M, Duh FM, Orcutt ML, Stackhouse T, Kuzmin I, Modi W, Geil L, et al. Identification of the von Hippel-Lindau disease tumor suppressor gene. Science. 1993 May 28;260(5112):1317-20. doi: 10.1126/science.8493574.
• Seizinger BR, Rouleau GA, Ozelius LJ, Lane AH, Farmer GE, Lamiell JM, Haines J, Yuen JW, Collins D, Majoor-Krakauer D, et al. Von Hippel-Lindau disease maps to the region of chromosome 3 associated with renal cell carcinoma. Nature. 1988 Mar 17;332(6161):268-9. doi: 10.1038/332268a0.
• Jemal A, Tiwari RC, Murray T, Ghafoor A, Samuels A, Ward E, Feuer EJ, Thun MJ; American Cancer Society. Cancer statistics, 2004. CA Cancer J Clin. 2004 Jan-Feb;54(1):8-29. doi: 10.3322/canjclin.54.1.8.
• Turkbey B, Lindenberg ML, Adler S, Kurdziel KA, McKinney YL, Weaver J, Vocke CD, Anver M, Bratslavsky G, Eclarinal P, Kwarteng G, Lin FI, Yaqub-Ogun N, Merino MJ, Linehan WM, Choyke PL, Metwalli AR. PET/CT imaging of renal cell carcinoma with (18)F-VM4-037: a phase II pilot study. Abdom Radiol (NY). 2016 Jan;41(1):109-18. doi: 10.1007/s00261-015-0599-1.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: October 20, 2012
• First Submitted That Met QC Criteria: October 20, 2012
• First Posted (Estimate): October 23, 2012

Study Record Updates

• Last Update Posted (Estimate): January 11, 2017
• Last Update Submitted That Met QC Criteria: January 10, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: RCC; Kidney Neoplasm; Biodistribution of 18F-VM4-037; CAIX Staining; Tumor Angiogenesis
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: 130018; 13-C-0018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO