Back to resultsImaging Studies of Kidney Cancer Using 18F-VM4-037
Primary Purpose
Carcinoma, Renal Cell, Kidney Neoplasms
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
18F-VM4-037
PET/CT
Sponsored by
About this trial
This is an interventional diagnostic trial for Carcinoma, Renal Cell focused on measuring Kidney Neoplasm, RCC, Biodistribution of 18F-VM4-037, CAIX Staining, Tumor Angiogenesis
Eligibility Criteria
- 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.
Sites / Locations
- National Institutes of Health Clinical Center, 9000 Rockville Pike
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Renal Cell Carcinoma
Arm Description
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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).
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).
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).
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.
Distribution Volume Ratio (DVR) for the Primary Kidney Lesions
DVR of the lesions was measured by the Logan graphical analysis method.
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.
Kinetic (Ki) Rate Constant
Ki was assessed by the Patlak graphical analysis method which measures the uptake rate constant Ki.
Full Information
NCT ID
NCT01712685
First Posted
October 20, 2012
Last Updated
January 10, 2017
Sponsor
National Cancer Institute (NCI)
1. Study Identification
Unique Protocol Identification Number
NCT01712685
Brief Title
Imaging Studies of Kidney Cancer Using 18F-VM4-037
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
January 2017
Overall Recruitment Status
Terminated
Why Stopped
Study was closed to accrual because imaging agent was no longer available.
Study Start Date
October 2012 (undefined)
Primary Completion Date
August 2013 (Actual)
Study Completion Date
August 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
National Cancer Institute (NCI)
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Renal Cell, Kidney Neoplasms
Keywords
Kidney Neoplasm, RCC, Biodistribution of 18F-VM4-037, CAIX Staining, Tumor Angiogenesis
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Renal Cell Carcinoma
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
18F-VM4-037
Intervention Description
Drug being tested for use in cancer imaging studies. It may help tumor tissue show up more clearly during scans.
Intervention Type
Procedure
Intervention Name(s)
PET/CT
Other Intervention Name(s)
Positron emission tomography, Computed tomography
Primary Outcome Measure Information:
Title
Level of Uptake of 18F-VM4-037 in Tumor and Non Tumor Tissues, Calculated as Standardized Uptake Values (SUVs)
Description
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.
Time Frame
58 days
Secondary Outcome Measure Information:
Title
Number of Participants With Adverse Events
Description
Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.
Time Frame
58 days
Title
Mean Standard Uptake Value (SUV) for All Target Lesions
Description
Mean SUV for all target lesions was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).
Time Frame
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.
Title
Mean Standard Uptake Value (SUV) for Primary Clear Cell Renal Carcinoma (ccRCC)
Description
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).
Time Frame
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.
Title
Mean Standard Uptake Value (SUV) for Normal Kidney
Description
Mean SUV for normal kidney was assessed by lesion based analysis to obtain SUV mean (the average SUV value within the lesion contour).
Time Frame
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.
Title
Number of Participants With a Mutation of the Von Hippel-Lindau (VHL) Gene
Description
Germline VHL mutation testing was performed using Clinical Laboratory Improvement Amendments (CLIA) certified laboratories.
Time Frame
21 days prior to enrollment until closure of the study, approximately 14 months.
Title
Distribution Volume Ratio (DVR) for the Primary Kidney Lesions
Description
DVR of the lesions was measured by the Logan graphical analysis method.
Time Frame
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.
Title
Time to Peak Activity Derived From Time Activity Curve (TAC)
Description
The time to peak activity of radiotracer (tumor marker) uptake indicates the optimal time to image to obtain best tumor visibility.
Time Frame
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.
Title
Kinetic (Ki) Rate Constant
Description
Ki was assessed by the Patlak graphical analysis method which measures the uptake rate constant Ki.
Time Frame
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adam R Metwalli, M.D.
Organizational Affiliation
National Cancer Institute (NCI)
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
14974761
Citation
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.
Results Reference
background
PubMed Identifier
8493574
Citation
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.
Results Reference
background
PubMed Identifier
2894613
Citation
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.
Results Reference
background
PubMed Identifier
26830617
Citation
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.
Results Reference
result
Links:
URL
http://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_2013-C-0018.html
Description
NIH Clinical Center Detailed Web Page
Learn more about this trial
Imaging Studies of Kidney Cancer Using 18F-VM4-037
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