Contrast-Enhanced Ultrasound for Kidney Cancer Subtyping and Staging

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04021238

Enrollment

Registered

2019-07-16

Start date

2020-10-07

Completion date

2022-08-05

Last updated

2023-11-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Kidney Cancer

Brief summary

The purpose of this study is to determine if contrast-enhanced ultrasound can detect abnormal features of kidney lesions in patients with suspected kidney cancer with the same accuracy as conventional ultrasound and contrast-enhanced magnetic resonance imaging (MRI)

Detailed description

This is a pilot cross-sectional study that compares contrast enhanced ultrasound to conventional ultrasound and contrasted MRI. Eligible patients will include anyone who has suspected kidney cancer and is scheduled for surgery, up to an anticipated total of 40 participants. Subject participation will be only for the day of CEUS study. There will be no follow-up period for this study. However, if results are encouraging, a longitudinal observational study may follow, and these same subjects would be eligible for enrollment. Eligible subjects will undergo a contrast enhanced ultrasound. Following completion of imaging, all CEUS, MRI (within 4 months) and B-mode (at time of CEUS) US studies will be de-identified. Blinded radiologists will interpret images and provide an overall assessment of risk of malignancy to each kidney using the Bosniak criteria for each kidney lesion present. The Bosniak criteria places cystic lesions into one of 5 categories (I, II, IIF, III and IV) based on lesion characteristics. CEUS based diagnosis will be compared to the diagnoses on routine B-mode US and contrast-enhanced MRI.

Interventions

DRUGPerflutren lipid microsphere

Baseline B-mode US will be performed to confirm the lesions being imaged (unless it is a subject with no lesions, then a basic B-mode US will be performed. Perflutren is a diagnostic drug that is intended to be used for contrast enhancement. The vial contains a clear, colorless, sterile, non-pyrogenic, hypertonic solution which is activated by mechanical agitation with Vialmix®.It will be dispensed in inactivated form to a study team member. The contrast agent will be activated just prior to administration (ideally to be used within 5 minutes of activation). Contrast agent Definity (or Lumason) will be activated according to package insert instructions, including use of VialMix®, the device used to activate Definity. Administration will occur IV in coordination with sonography staff trained specifically in contrast ultrasound imaging.The total imaging time is anticipated to be less than 30 minutes.

DRUGSulfur hexafluoride lipid microspheres

Baseline B-mode US will be performed to confirm the lesions being imaged (unless it is a subject with no lesions, then a basic B-mode US will be performed. Lumason will be used as a secondary contrast agent only if Definity(perflutren) is unavailable.This drug will be administered using the dosing range and administration type within the Lumason prescribing information. The contrast agent will be activated just prior to administration (ideally to be used within 5 minutes of activation). Contrast agent Definity (or Lumason) will be activated according to package insert instructions, including use of VialMix®, the device used to activate Definity. Administration will occur IV in coordination with sonography staff trained specifically in contrast ultrasound imaging.The total imaging time is anticipated to be less than 30 minutes.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

DIAGNOSTIC

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 99 Years

Healthy volunteers

Inclusion criteria

* A suspected diagnosis of kidney cancer with a solid or partially solid lesion and planned surgical nephrectomy within 3 months before surgery * Able to provide informed consent * Willing to comply with protocol requirements * At least 18 years of age

Exclusion criteria

* Critically ill or medically unstable or in an intensive care setting and whose critical course during a potential observation period would be unpredictable * Known hypersensitivity to sulfur hexafluoride or to any component of perflutren lipid (Definity®) or sulfur hexafluoride (Lumason®) * Right to left shunt, severe pulmonary hypertension (Pulmonary artery pressure \>90mmHg), or adult respiratory distress syndrome * Has any other medical condition or other circumstances that would significantly decrease the chances of obtaining reliable data or of achieving the study objectives * Unstable cardiopulmonary disease including any of the following: * Severe congestive heart failure (class IV in accordance with the classification of the New York Heart Association) * Unstable angina * Symptomatic arrhythmia (i.e. tachycardia, bradycardia, supraventricular tachycardia, ventricular fibrillation, ventricular tachycardia, atrial flutter or fibrillation) * Myocardial infarction within 14 days prior to the date of proposed microbubble administration. * Any woman who is pregnant or has reason to believe she is pregnant (the possibility of pregnancy has to be excluded by negative urine β-HCG results, obtained the same day as the CEUS, or on the basis of patient history, e.g.: tubal ligation, hysterectomy or a minimum of 1 year without menses) * Obesity that limits obtainment of acceptable images

Design outcomes

Primary

Measure	Time frame	Description
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Volume	Baseline- up to 3 minutes	The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated volume parameter was studied. The volumes were generated using the ellipsoid equation on the CEUS image of the kidney mass.
3D CEUS Generated Metric in Kidney Mass: FR_a	Baseline- up to 3 minutes	A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) FR\_a parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=white. The intensity was plotted by time. FR\_a parameters were devised from an exponential fit. The exponential fit of the data provides the height of the curve.
3D CEUS Generated Metric in Kidney Mass: FR_beta	Baseline- up to 3 minutes	A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) FR\_beta parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, 255=White. The intensity was plotted by time. FR\_beta parameters were devised from an exponential fit. Exponential fit of the data provides the slope of the curve.
3D CEUS Generated Metric in Kidney Mass: Volume	Baseline- up to 3 minutes	A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) volume parameter was generated. The volumes were generated using the ellipsoid equation on the CEUS image of the kidney mass.
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Wash_In_Slope	Baseline- up to 3 minutes	The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated Wash\_In\_Slope parameter was studied. This metric indicates the change in contrast intensity with time in the mass using bolus imaging. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The Wash\_In\_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of the curve.
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Wash_In_intercept	Baseline- up to 3 minutes	The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated Wash\_In\_intercept parameter was studied. This metric indicates the intensity level prior to infusion of contrast. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. This value was calculated using an equation for a line which has a slope and the intercept. The values were negative because they were calculated (not measured).
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Wash_Out_Slope	Baseline- up to 3 minutes	The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated Wash\_Out\_Slope parameter was studied. This metric indicates the change in contrast intensity with time in the mass using bolus imaging. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. Decreasing brightness is related to the slope of the curve. The Wash Out slope decreases as the contrast agent clears the body/mass. Decreasing brightness is related to the slope of the curve. This results in a negative number. This value was generated by fitting the data to a linear equation.
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. Wash_Out_Intercept	Baseline- up to 3 minutes	The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated Wash\_Out\_Intercept parameter was studied. This metric indicates the intensity level of contrast at steady state of enhancement in the mass. The contrast-enhanced ultrasonogram (CEUS) Wash\_Out\_Intercept parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. This value was calculated using an equation for a line which has a slope and the intercept.
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. FR_a	Baseline- up to 3 minutes	The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated FR\_a parameter was studied. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The intensity was plotted by time. FR\_a parameters were devised from an exponential fit. The exponential fit of the data provides the height of the curve.
3D CEUS Generated Metric in Kidney Mass - Histopathologic Type vs. FR_beta	Baseline- up to 3 minutes	The association between tumor pathology type (Clear cell renal carcinoma (CCRCC) versus none (CCRCC) pathology) and CEUS-generated FR\_ beta parameter was studied. The contrast-enhanced ultrasonogram (CEUS) FR\_beta parameter was generated. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The intensity was plotted by time. FR\_beta parameters were devised from an exponential fit. The exponential fit of the data provides the slope of the curve.
3D CEUS Generated Metrics in Kidney Mass: Wash_In_Slope	Baseline- up to 3 minutes	A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash\_In\_Slope parameter was generated. This metric indicates the change in contrast with time in the mass using bolus imaging. Bolus imaging injects a small amount of contrast agent and monitors the contrast agent as it flows in (wash-in) and out (wash-out) of the body/mass. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White.The Wash\_In\_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of curve.
3D CEUS Generated Metric in Kidney Mass: Wash_In_intercept	Baseline- up to 3 minutes	A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash\_In\_intercept parameter was generated. This metric indicates the intensity level prior to infusion of contrast. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=white. This value was calculated using an equation for a line which has a slope and the intercept. The values were negative because they were calculated (not measured).
3D CEUS Generated Metric in Kidney Mass: Wash_Out_Slope	Baseline- up to 3 minutes	A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash\_Out\_Slope parameter was generated. This metric indicates the change in contrast with time in the mass using bolus imaging. Bolus imaging injects a small amount of contrast agent and monitors the contrast agent as it flows in (wash-in) and out (wash-out) of the body/mass. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) value range was between 0=black and 255=White. The wash Out slope decreases as the contrast agent clears the body/mass. Decreasing brightness is related to the slope of the curve. This results in a negative number. This value was generated by fitting the data to a linear equation.
3D CEUS Generated Metric in Kidney Mass: Wash_Out_Intercept	Baseline- up to 3 minutes	A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) Wash\_Out\_Intercept parameter was generated. This metric indicates the intensity level of contrast at a steady state of enhancement in the mass. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. This value was calculated using an equation for a line that has a slope and an intercept.

Secondary

Measure	Time frame	Description
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Wash_In_intercept	Baseline- up to 3 minutes	The association between tumor stage and CEUS-generated Wash\_In\_intercept parameter was studied. These values were generated by fitting the data to a linear equation. This metric indicates the intensity level prior to infusion of contrast. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. This value was calculated using an equation for a line that has a slope and an intercept. The values were negative because they were calculated (not measured). Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size \>7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Wash_Out_Slope	Baseline- up to 3 minutes	The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated Wash\_Out\_Slope parameter was studied. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The Wash\_Out\_Slope decreases as the contrast agent clears the body/mass. Decreasing brightness is related to the slope of the curve. This results in a negative number. This value was generated by fitting the data to a linear equation. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the AJCC. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size \>7 cm, Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Wash_Out_Intercept	Baseline- up to 3 minutes	The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated Wash\_Out\_Intercept parameter was studied. This metric indicates the intensity level of contrast at a steady state of enhancement in the mass. The contrast-enhanced ultrasonogram (CEUS) Wash\_Out\_Intercept parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=White. This value was calculated using an equation for a line that has a slope and the intercept. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size \>7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. FR_a	Baseline- up to 3 minutes	The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated FR\_a parameter was studied. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The intensity was plotted by time. FR\_a parameters were devised from an exponential fit. The exponential fit of the data provides the height of the curve. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size \>7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. FR_beta	Baseline- up to 3 minutes	The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated FR\_ beta parameter was studied. The contrast-enhanced ultrasonogram (CEUS) FR\_beta parameter was generated. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The intensity was plotted by time. FR\_beta parameters were devised from an exponential fit. The exponential fit of the data provides the slope of the curve. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size \>7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Volume	Baseline- up to 3 minutes	The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated volume was studied. The contrast-enhanced ultrasonogram (CEUS) volume was generated. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size \>7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.
Pooled Kidney Mass Stage vs. 3D CEUS-generated Wash in Metrics	Baseline- up to 3 minutes	The association between pooled tumor stage (tumor stages 0,1,2 versus tumor stage 3) and CEUS-generated Wash\_In\_Slope parameter was studied. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal values range between 0=black and 255=White. The Wash\_In\_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of the curve. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the American Joint Cancer Committee. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size \>7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.
Pooled Kidney Mass Stage Using 3D CEUS-generated Wash Out Metrics	Baseline- up to 3 minutes	The association between pooled tumor stage (tumor stages 0,1,2 versus tumor stage 3) and CEUS-generated Wash\_Out\_Slope parameter was studied. The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black, and 255=White. The Wash\_Out\_Slope decreases as the contrast agent clears the body/mass. Decreasing brightness is related to the slope of the curve. This results in a negative number. This value was generated by fitting the data to a linear equation. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to the AJCC. All masses in this study were in stage 0, I, II, or III (not stage IV). Stage 0 = cancer cell was not found, Stage I = tumor size ≤7 cm, Stage II = tumor size \>7 cm, Stage III includes tumors growing into a major vein or tissue, with no spread to lymph nodes.
3D CEUS Generated Metric in Kidney Mass - Tumor Stage vs. Wash_In_Slope	Baseline- up to 3 minutes	The intensity of the signal (the brightness of the image) is plotted over time to generate the time-intensity curve. The intensity of the signal (the brightness of the image) values range between 0=black and 255=White. The Wash\_In\_Slope increases as the contrast agent is introduced to the body/mass. This value was generated by fitting the data to a linear equation. Increasing brightness is related to the slope of the curve. The association between tumor stage (Tumor stage 0,1,2,3) and CEUS-generated Wash\_In\_Slope parameter was studied. Tumor staging is based on the size of the mass, spread to lymph nodes, and metastasis to distant sites according to American Joint Cancer Committee. All masses in this study were in stage 0, I, II or III (not stage IV). Stage 0 = cancer cell was not found on pathology. Stage I =tumors size ≤7 cm. Stage II = tumor size \>7 cm. Stage III includes tumors that are growing into a major vein or tissue around the kidney with no spread to lymph nodes.

Countries

United States

Participant flow

Recruitment details

Between 10/7/2020- 7/22/2022, 25 subjects consented and enrolled in the study at one center in North Carolina.

Pre-assignment details

A total of 25 subjects were found eligible and consented to the study. One subject was withdrawn after enrollment and did not complete study imaging and 24 subjects enrolled in the study and underwent research imaging.

Participants by arm

Arm	Count
Perflutren Lipid Microsphere or Lumason Subjects with suspected kidney cancer and planned surgery were imaged using Definity® containing perflutren lipid microsphere contrast-enhanced ultrasound (US). Baseline B-mode US was performed to confirm the lesions being imaged.	24
Total	24

Baseline characteristics

Characteristic	Perflutren Lipid Microsphere or Lumason
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	8 Participants
Age, Categorical Between 18 and 65 years	16 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants
Race (NIH/OMB) Asian	0 Participants
Race (NIH/OMB) Black or African American	6 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	0 Participants
Race (NIH/OMB) White	16 Participants
Region of Enrollment United States	24 participants
Sex: Female, Male Female	5 Participants
Sex: Female, Male Male	19 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 25
other Total, other adverse events	0 / 25
serious Total, serious adverse events	0 / 25

Outcome results

Primary

3D CEUS Generated Metric in Kidney Mass: FR_a

A study-specific model was created to predict kidney tumor type. The contrast-enhanced ultrasonogram (CEUS) FR\_a parameter was generated. The intensity of the signal (the brightness of the image) value range is between 0=black, and 255=white. The intensity was plotted by time. FR\_a parameters were devised from an exponential fit. The exponential fit of the data provides the height of the curve.