Contrast-Enhanced Subharmonic Ultrasound Imaging in Improving Characterization of Adnexal Masses in Patients Undergoing Surgery

• Sponsor: Sidney Kimmel Cancer Center at Thomas Jefferson University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03297112
• Collaborator: National Institutes of Health (NIH) (NIH), Lantheus Medical Imaging (Industry)
• Enrollment: 12
• Location: 1
• Arm: 1
• Actual Duration (Months): 13.1
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

This pilot clinical trial studies how well contrast-enhanced subharmonic ultrasound imaging works in improving the characterization of adnexal masses in patients undergoing surgery. Contrast-enhanced subharmonic ultrasound imaging uses high-frequency sound waves to produce images of internal organs and when combined with an ultrasound agent such as perflutren lipid microspheres, may help improve imaging and management of adnexal masses.

Condition or Disease	Intervention/Treatment	Phase
Adnexal Mass	Drug: Perflutren Lipid Microspheres; Procedure: Contrast-Enhanced Subharmonic Ultrasound Imaging	Early Phase 1

Detailed Description

PRIMARY OBJECTIVES:

1. To develop qualitative subharmonic imaging (SHI) or SHI-derived quantitative biomarkers.

2. To generate pilot data for a study to evaluate if they improve the characterization of benign and malignant adnexal masses compared to standard ultrasound or contrast enhanced magnetic resonance imaging (MRI) or the risk of malignancy index (RMI).

SECONDARY OBJECTIVES:

1. To compare the SHI depiction of adnexal masses' neovascularity in humans to intra-tumoral microvascular density (iMVD) obtained from CD31 an immunohistochemical marker of angiogenesis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Subharmonic Contrast Ultrasound for Improved Characterization for Adnexal Masses-A Pilot Study
• Actual Study Start Date: Aug 1, 2017
• Actual Primary Completion Date: Sep 4, 2018
• Actual Study Completion Date: Sep 4, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: contrast-enhanced subharmonic ultrasound imaging Patients receive perflutren lipid microspheres IV. After 15 minutes, patients receive perflutren lipid microspheres IV again over 5 minutes and undergo contrast-enhanced subharmonic ultrasound imaging over 60 minutes.	Drug: Perflutren Lipid Microspheres; Given IV; Other Names: Definity ; Procedure: Contrast-Enhanced Subharmonic Ultrasound Imaging; Undergo contrast-enhanced subharmonic ultrasound imaging

Outcome Measures

Primary Outcome Measures

1. Diagnostic Accuracy of Subharmonic Ultrasound Imaging Compared to Standard Ultrasound or Contrast Enhanced Magnetic Resonance Imaging (MRI) [Baseline scan to day of surgery]

   The techniques will be compared using an analysis of variance (ANOVA) method (i.e., baseline ultrasound imaging, SHI, or MRI) as the dependent variable and outcome as the independent variables. Diagnostic accuracy of lesion identification as "no lesion seen", "definitely benign", "indeterminate" or "definitely malignant" based on independent reads by experience radiologists for SHI with and without contrast vs contrast-enhanced MRI (quantitative analysis). For qualitative analysis, digital images from the SHI imaging were reviewed by the independent radiologists for interpretation. Diagnostic accuracy reported as percentage of lesions correctly identified through SHI as compared to ultrasound or MRI as the gold standard.

2. Accuracy of SHI Characterization Compared to the Risk of Malignancy Index [Baseline scan to day of surgery]

   The ability of SHI to accurately characterize lesions as benign from malignant masses as compared to other imaging (ultrasound or MRI) and pathology will be analyzed using logistic regression and receiver operating characteristic (ROC) analyses.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Be diagnosed with an adnexal mass

• Be scheduled for surgery to remove the adnexal mass

• Be clinically stable

• If a female of child-bearing potential, must have a negative pregnancy test

• Be conscious and able to comply with study procedures

• Have read and signed the Institutional Review Board (IRB)-approved informed consent form for participating in the study

Exclusion Criteria:

• Females who are pregnant or nursing

• Patients who have received an investigational drug in the 30 days before study drug administration, or will receive one within 72 hours (h) afterwards

• Patients with known or suspected right-to-left, bi-directional, or transient right-to-left cardiac shunts

• Patients with pulmonary hypertension or unstable cardiopulmonary conditions

• Patients currently on chemotherapy or with other primary cancers requiring systemic or hepatic loco-regional treatment

• Patients who are clinically unstable, patients who are seriously or terminally ill with a life expectancy of less than 1 month, and patients whose clinical course are unpredictable; for example:

• Patients on life support or in a critical care unit

• Patients with unstable occlusive disease (e.g., crescendo angina)

• Patients with clinically unstable cardiac arrhythmias, such as recurrent ventricular tachycardia

• Patients with uncontrolled congestive heart failure (New York Heart Association [NYHA] class IV)

• Patients with recent cerebral hemorrhage

• Patients who have undergone surgery within 24 hours prior to the study sonographic examination

• Patients with a history of anaphylactic allergy to Definity, manifested by one or more of the following symptoms: generalized urticaria, difficulty in breathing, swelling of the mouth and throat, hypotension, or shock

• Patients with congenital heart defects

• Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary emboli

• Patients with respiratory distress syndrome

• Patients with thrombosis within the splenic vein

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Cancer Center at Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107

Sponsors and Collaborators

• Sidney Kimmel Cancer Center at Thomas Jefferson University
• National Institutes of Health (NIH)
• Lantheus Medical Imaging

Investigators

• Principal Investigator: Flemming Forsberg, PhD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 12, 2016

More Information

Additional Information:

• Sidney Kimmel Cancer Center
• Thomas Jefferson University Hospital

Publications

None provided.

• Responsible Party: Sidney Kimmel Cancer Center at Thomas Jefferson University
• ClinicalTrials.gov Identifier: NCT03297112
• Other Study ID Numbers: 16F.394
• First Posted: Sep 29, 2017
• Last Update Posted: Sep 25, 2019
• Last Verified: Sep 1, 2019

• 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

Study Results

Participant Flow

Arm/Group Title	Contrast-enhanced Subharmonic Ultrasound Imaging
Arm/Group Description	Patients receive perflutren lipid microspheres IV. After 15 minutes, patients receive perflutren lipid microspheres IV again over 5 minutes and undergo contrast-enhanced subharmonic ultrasound imaging over 60 minutes. Perflutren Lipid Microspheres: Given IV Contrast-Enhanced Subharmonic Ultrasound Imaging: Undergo contrast-enhanced subharmonic ultrasound imaging
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Contrast-enhanced Subharmonic Ultrasound Imaging
Arm/Group Description	Patients receive perflutren lipid microspheres IV. After 15 minutes, patients receive perflutren lipid microspheres IV again over 5 minutes and undergo contrast-enhanced subharmonic ultrasound imaging over 60 minutes. Perflutren Lipid Microspheres: Given IV Contrast-Enhanced Subharmonic Ultrasound Imaging: Undergo contrast-enhanced subharmonic ultrasound imaging
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	9 75%
>=65 years	3 25%
Sex: Female, Male (Count of Participants)
Female	12 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	12 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 8.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	11 91.7%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Diagnostic Accuracy of Subharmonic Ultrasound Imaging Compared to Standard Ultrasound or Contrast Enhanced Magnetic Resonance Imaging (MRI)
Description	The techniques will be compared using an analysis of variance (ANOVA) method (i.e., baseline ultrasound imaging, SHI, or MRI) as the dependent variable and outcome as the independent variables. Diagnostic accuracy of lesion identification as "no lesion seen", "definitely benign", "indeterminate" or "definitely malignant" based on independent reads by experience radiologists for SHI with and without contrast vs contrast-enhanced MRI (quantitative analysis). For qualitative analysis, digital images from the SHI imaging were reviewed by the independent radiologists for interpretation. Diagnostic accuracy reported as percentage of lesions correctly identified through SHI as compared to ultrasound or MRI as the gold standard.
Time Frame	Baseline scan to day of surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Contrast-enhanced Subharmonic Ultrasound Imaging
Arm/Group Description	Patients receive perflutren lipid microspheres IV. After 15 minutes, patients receive perflutren lipid microspheres IV again over 5 minutes and undergo contrast-enhanced subharmonic ultrasound imaging over 60 minutes. Perflutren Lipid Microspheres: Given IV Contrast-Enhanced Subharmonic Ultrasound Imaging: Undergo contrast-enhanced subharmonic ultrasound imaging
Measure Participants	12
Measure lesions	12
Qualitative analysis of CEUS SHI with contrast	70
Qualitative analysis of CEUS SHI without contrast	56

2. Primary Outcome

Title	Accuracy of SHI Characterization Compared to the Risk of Malignancy Index
Description	The ability of SHI to accurately characterize lesions as benign from malignant masses as compared to other imaging (ultrasound or MRI) and pathology will be analyzed using logistic regression and receiver operating characteristic (ROC) analyses.
Time Frame	Baseline scan to day of surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Contrast-enhanced Subharmonic Ultrasound Imaging
Arm/Group Description	Patients receive perflutren lipid microspheres IV. After 15 minutes, patients receive perflutren lipid microspheres IV again over 5 minutes and undergo contrast-enhanced subharmonic ultrasound imaging over 60 minutes. Perflutren Lipid Microspheres: Given IV Contrast-Enhanced Subharmonic Ultrasound Imaging: Undergo contrast-enhanced subharmonic ultrasound imaging
Measure Participants	12
Number [percent accurate m lesion identification]	73

Adverse Events

Time Frame	30 minutes after the second Definity injection
Arm/Group Title	Contrast-enhanced Subharmonic Ultrasound Imaging
Arm/Group Description	Patients receive perflutren lipid microspheres IV. After 15 minutes, patients receive perflutren lipid microspheres IV again over 5 minutes and undergo contrast-enhanced subharmonic ultrasound imaging over 60 minutes. Perflutren Lipid Microspheres: Given IV Contrast-Enhanced Subharmonic Ultrasound Imaging: Undergo contrast-enhanced subharmonic ultrasound imaging
All Cause Mortality
	Contrast-enhanced Subharmonic Ultrasound Imaging
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Serious Adverse Events
	Contrast-enhanced Subharmonic Ultrasound Imaging
	Affected / at Risk (%)	# Events
Total	0/12 (0%)
Other (Not Including Serious) Adverse Events
	Contrast-enhanced Subharmonic Ultrasound Imaging
	Affected / at Risk (%)	# Events
Total	0/12 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.