Two and Three Dimensional Contrast-enhanced Ultrasound for Screening of Renal Cell Carcinoma Recurrence Following Cryoablation

Two and Three Dimensional Contrast-Enhanced Ultrasound for Screening of Renal Cell Carcinoma Recurrence Following Cryoablation

The purpose of the proposed trial is to determine whether contrast-enhanced ultrasound (CEUS) can be used to assess the recurrence of renal cell carcinoma (RCC) after cryoablation compared to contrast enhanced CT or MR (the standard evaluation). This study involves the off-label use of an FDA-approved ultrasound contrast agent, Optison that flows in the vascularity. CEUS will be performed by both two and three dimensional ultrasound to examine post-cryoablation vascularity changes to screen for recurrent disease.

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: Optison

Detailed Description

Subjects eligible for trial enrollment will be identified by the Thomas Jefferson University Urology group from their patient population of subjects under active surveillance for recurrence of a previously cryoablated RCC. A research coordinator will explain the study to the patient. The patient will be given time to consider the risks and benefits of the study and ask questions about participation. The coordinator will review the consent form with the patient and then the patient will be given the form to review. The patient, coordinator, and a study investigator will all sign the consent form. The patient will be given a copy of the signed consent form for their records.

Screening assessments will be performed prior to CEUS imaging. Trial participants will have the presence of inclusion criteria and absence of exclusion criteria verified by providing a medical history. A full demographic profile, known drug allergies or intolerances, and a review of the subject's medical/surgical history will be recorded. If the subject is a woman of childbearing age, she will have a urine pregnancy test (the results of which will be made available to the subject prior to study initiation).

All contrast injections will be supervised by a board certified physician. Resuscitation equipment and trained personnel will be in immediate proximity to the patient during each CEUS exam. The ultrasound examinations will be performed by a qualified sonographer. Ultrasound exams will take place the morning prior to the patient's 8, 12, 18, 24, or 36 month CT/MRI follow up (scheduled as part of their clinical care) or during their consultation in Jefferson's Urology clinic (for patients who have imaging performed outside Jefferson). Procedures and equipment for this trial will be used in accordance with typical clinical procedures. All trial procedures will be conducted in accordance with Good Clinical Practice. For the ultrasound examination, the patient will be asked to lie in the supine position and a catheter will be placed in a superficial vein (preferably an antecubital vein). Acoustic coupling gel will be applied to the area of interest. A state of the art ultrasound scanner with 2D and 3D curvilinear probes will be used.

A baseline ultrasound grayscale scan will be used to identify the tumor and to evaluate the following criteria: size, shape, and orientation of the lesion; echogenicity compared to surrounding tissue. Standard power Doppler of the lesion will also be performed. When possible, previous MR/CT data will be uploaded onto the scanner in order to perform image fusion for ultrasound guidance during imaging. The distribution of color signals and the overall color content of the tumor will be evaluated by comparing the pattern and amount of color to the normal surrounding tissue. Following baseline scanning, patients will receive a 1 ml intravenous injection of Optison (GE Healthcare, Princeton, NJ) in a peripheral vein followed by renal mass imaging in 2D CHI (a nonlinear contrast imaging package). Ten minutes after the 2D CEUS exam, patients will receive a second bolus injection of Optison followed by 3D CHI (using a curvilinear 3D array). All contrast injections will be supervised by a board certified physician. Resuscitation equipment and trained personnel will be immediate proximity to the patient during each contrast-enhanced ultrasound exam. Digital clips of the exams will be recorded through the contrast agent wash-in and wash-out phases for at least two minutes and stored for later use. The subject will then be monitored for adverse reactions for 30 minutes. If the patient wishes to continue participating in the study, they will be eligible for CEUS exams during their future clinically scheduled follow up exams as long as these take place within the study timeframe.

Patients will be monitored for AEs during and 30 minutes after contrast administration. All other procedures will be performed according to standard of care. No further patient monitoring is required as side effects of Optison are acute in nature and no renal toxicity has been reported.

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University

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:

• Previously received cryotherapy of RCC.
• Be scheduled for contrast-enhanced MRI/CT to monitoring of RCC recurrence as part of their 8, 12, 18, 24, or 36 month CT/MRI follow up.
• Be at least 18 years of age.
• Be medically stable.
• If a female of child-bearing age, must have a negative pregnancy test.
• Have signed Informed Consent to participate in the study.

Exclusion Criteria:

• Females who are pregnant or nursing.
• Patients who are medically unstable, patients who are seriously or terminally ill, and patients whose clinical course is unpredictable. For example:
• Patients on life support or in a critical care unit.
• Patients with unstable occlusive disease (eg, crescendo angina)
• Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia.
• Patients with uncontrolled congestive heart failure (NYHA Class IV)
• Patients with recent cerebral hemorrhage.
• Patients with known sensitivities to albumin, blood, or blood products
• Patients who have undergone surgery within 24 hours prior to the study sonographic examination.
• Patients with known hypersensitivity to perflutren
• Patients with cardiac shunts.
• Patients with congenital heart defects.
• Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli.
• Patients with respiratory distress syndrome.

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: Contrast Ultrasound Reccurence Screening; Patients scheduled for MRI/CT follow up of a renal cancer previously treated by cryoablation therapy who will also undergo a contrast-enhanced ultrasound exam. This is a one-time imaging study and contrast ultrasound exams will be compared to the clinically scheduled MRI/CT.	Drug: Optison; Optison is an ultrasound contrast agent. The agent is a blood pooling agent administered via catheter and provides improved ultrasound visualization of the vasculature.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Sensitivity of Detecting RCC Recurrence (Using Contrast-enhanced MRI as a Reference Standard) on a Single Contrast-enhanced Ultrasound Exam.	Patients scheduled for follow up contrast enhanced computed tomography (CT) or magnetic resonance imaging (MRI) of a previously cryoablatated renal cell carcinoma (RCC) through Thomas Jefferson University's Urology clinic will undergo a single ultrasound exam using contrast enhanced ultrasound. Ultrasound imaging will be performed using a state of the art ultrasound scanner with two and three dimensional curvilinear transducers.	8 months post cryoblation

Collaborators and Investigators

• Sponsor: Thomas Jefferson University

Publications and helpful links

General Publications

• Eisenbrey JR, Shaw CM, Lyshchik A, Machado P, Lallas CD, Trabulsi EJ, Merton DA, Fox TB, Liu JB, Brown DB, Forsberg F. Contrast-Enhanced Subharmonic and Harmonic Ultrasound of Renal Masses Undergoing Percutaneous Cryoablation. Acad Radiol. 2015 Jul;22(7):820-6. doi: 10.1016/j.acra.2015.03.008. Epub 2015 Apr 14.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2015
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): June 21, 2018

Study Registration Dates

• First Submitted: May 4, 2015
• First Submitted That Met QC Criteria: May 6, 2015
• First Posted (Estimate): May 12, 2015

Study Record Updates

• Last Update Posted (Actual): May 7, 2019
• Last Update Submitted That Met QC Criteria: April 29, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: ultrasonography; cryosurgery
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Disease Attributes; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma; Recurrence
• Other Study ID Numbers: 15P.039

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes