Carcinoma, Renal Cell, Kidney Neoplasms
Conditions
Keywords
Kidney Neoplasm, RCC, Biodistribution of 18F-VM4-037, CAIX Staining, Tumor Angiogenesis
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.
Interventions
DRUG18F-VM4-037
Drug being tested for use in cancer imaging studies. It may help tumor tissue show up more clearly during scans.
PROCEDUREPET/CT
Sponsors
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Renal Cell Carcinoma This is a single arm, phase II trial of a novel radiotracer that is being evaluated for use in patients with kidney cancer. This study is designed to evaluate the imaging characteristics of this drug for detecting specific types of kidney cancer. This is a single administration trial of a single dose of the drug (18F-VM4-037: Drug being tested for use in cancer imaging studies; it may help tumor tissue show up more clearly during scans.) followed by imaging to assess distribution of the drug in normal and tumor tissue. | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | pt declined to participate before trmt | 1 |
Baseline characteristics
| Characteristic | Renal Cell Carcinoma |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants |
| Age, Continuous | 56.62 years STANDARD_DEVIATION 14.26 |
| Clinical Stage T1aNOMO | 7 Participants |
| Clinical Stage T1bNOMO | 1 Participants |
| Clinical Stage T2NOMO1 | 1 Participants |
| Clinical Stage T3aNOM1 | 2 Participants |
| Clinical Stage TONOMO | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Gender Female | 3 Participants |
| Gender Male | 9 Participants |
| Grade 2 | 8 Participants |
| Grade 3 | 1 Participants |
| Grade 4 | 2 Participants |
| Grade Not Applicable (N/A) | 1 Participants |
| Histology ccRCC with sarcomatoid differentiation | 1 Participants |
| Histology ccRCC with sarcomatoid features | 1 Participants |
| Histology Clear Renal Cell Carcinoma (ccRCC) | 9 Participants |
| Histology Renalcyst | 1 Participants |
| Known Hereditary Renal Cell Carcinoma Mutation No | 7 Participants |
| Known Hereditary Renal Cell Carcinoma Mutation Yes (Von Hippel-Lindau) | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment United States | 12 Participants |
| Tumor Size (cm) 2.0 | 1 Participants |
| Tumor Size (cm) 2.7 | 1 Participants |
| Tumor Size (cm) 3.3 | 1 Participants |
| Tumor Size (cm) 3.4 | 2 Participants |
| Tumor Size (cm) 3.5 | 1 Participants |
| Tumor Size (cm) 3.6 | 1 Participants |
| Tumor Size (cm) 3.7 | 1 Participants |
| Tumor Size (cm) 4.0 | 1 Participants |
| Tumor Size (cm) 5.8 | 1 Participants |
| Tumor Size (cm) 6.89 | 1 Participants |
| Tumor Size (cm) 9.3 | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
Primary
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.
Time frame: 58 days
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Renal Cell Carcinoma | Level of Uptake of 18F-VM4-037 in Tumor and Non Tumor Tissues, Calculated as Standardized Uptake Values (SUVs) | Tumor tissue | 6.2 Standardized uptake value | Standard Error 0.25 |
| Renal Cell Carcinoma | Level of Uptake of 18F-VM4-037 in Tumor and Non Tumor Tissues, Calculated as Standardized Uptake Values (SUVs) | Nontumor tissue | 5.6 Standardized uptake value | Standard Error 0.2 |
| Renal Cell Carcinoma | Level of Uptake of 18F-VM4-037 in Tumor and Non Tumor Tissues, Calculated as Standardized Uptake Values (SUVs) | Muscle tissue | 0.6 Standardized uptake value | Standard Error 0.21 |
| Renal Cell Carcinoma | Level of Uptake of 18F-VM4-037 in Tumor and Non Tumor Tissues, Calculated as Standardized Uptake Values (SUVs) | Normal kidney tissue | 35 Standardized uptake value | Standard Error 3.69 |
Secondary
Distribution Volume Ratio (DVR) for the Primary Kidney Lesions
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Cell Carcinoma | Distribution Volume Ratio (DVR) for the Primary Kidney Lesions | 5.2 Distribution volume ratio | Standard Deviation 2.8 |
Secondary
Kinetic (Ki) Rate Constant
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Renal Cell Carcinoma | Kinetic (Ki) Rate Constant | Primary kidney lesions | 0.01 1/Minutes | Standard Deviation 0.05 |
| Renal Cell Carcinoma | Kinetic (Ki) Rate Constant | Normal kidney | .45 1/Minutes | Standard Deviation 0.22 |
| Renal Cell Carcinoma | Kinetic (Ki) Rate Constant | Liver | 0.54 1/Minutes | Standard Deviation 0.18 |
Secondary
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).
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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Renal Cell Carcinoma | Mean Standard Uptake Value (SUV) for All Target Lesions | 3.04 Standard uptake value (SUV) |
Secondary
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).
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.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Renal Cell Carcinoma | Mean Standard Uptake Value (SUV) for Normal Kidney | 35.4 Standard uptake value (SUV |
Secondary
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).
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.
Population: Mean SUV for ccRCC after excluding Bosnial 3 Cyst (e.g. Bosnial 3 complex cyst) in one participant.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Renal Cell Carcinoma | Mean Standard Uptake Value (SUV) for Primary Clear Cell Renal Carcinoma (ccRCC) | 2.55 Standard uptake value (SUV |
Secondary
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.
Time frame: 58 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Cell Carcinoma | Number of Participants With Adverse Events | 2 participants |
Secondary
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.
Time frame: 21 days prior to enrollment until closure of the study, approximately 14 months.
Population: 5/11 participants had germline VHL testing with 4 having identifiable mutations of the VHL gene. 6/11 participants did not have germline VHL mutation testing due to low index of clinical suspicion although 2/6 had germline analysis for other gene mutations linked to familial renal cell carcinoma conditions.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Renal Cell Carcinoma | Number of Participants With a Mutation of the Von Hippel-Lindau (VHL) Gene | 4 participants |
Secondary
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.
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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Renal Cell Carcinoma | Time to Peak Activity Derived From Time Activity Curve (TAC) | 9.08 Minutes | Standard Deviation 3.06 |