Perflutren Protein-Type A Microspheres and Contrast-Enhanced Ultrasound in Improving Response to Radioembolization Therapy in Patients With Liver Cancer

Ultrasound Microbubble Destruction and Perfusion Quantification for Improving Radioembolization Therapy of Hepatocellular Carcinoma

This phase II trial studies how well perflutren protein-type A microspheres and contrast-enhanced ultrasound work in improving response to radioembolization therapy in patients with liver cancer. Ultrasound contrast agents, such as perflutren protein-type A microspheres, use gas microbubbles to improve image quality. Using contrast-enhanced ultrasound imaging will "pop" these microbubbles and cause tumors to become more sensitive to radiation therapies.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Procedure: Dynamic Contrast-Enhanced Ultrasound Imaging; Procedure: Yttrium-90 Microsphere Radioembolization; Drug: Perflutren Protein-Type A Microspheres

Detailed Description

PRIMARY OBJECTIVE:

I. Characterize the ability of localized ultrasound contrast agent destruction to improve hepatocellular carcinoma (HCC) response to yttrium Y-90 (Y90) radioembolization.

SECONDARY OBJECTIVE:

I. Determine if contrast-enhanced ultrasound estimated tumor perfusion can reliably predict HCC response to radioembolization 1-14 days post treatment.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive perflutren protein-type A microspheres intravenously (IV) over 10 minutes and undergo contrast-enhanced ultrasound (CEUS) over 60 minutes at 1-6 hours and at approximately 7 and 14 days after yttrium Y-90 radioembolization.

GROUP II: Patients undergo standard of care yttrium Y-90 radioembolization.

After completion of study treatment, patients are followed up at 1 month and at 3-4 months.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: John Eisenbrey, PhD; Phone Number: (215) 503-5188; Email: john.eisenbrey@jefferson.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sidney Kimmel Cancer Center at Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Be scheduled for sub-lobar radioembolization therapy of a previously untreated HCC mass < 6 cm visible on grayscale ultrasound
• Be medically stable
• If a female of child-bearing age, have a negative pregnancy test prior to each ultrasound exam
• 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 (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 with known sensitivities to albumin, blood, or blood products
• Patients with known hypersensitivity to perflutren
• Patients with known cardiac shunts
• Patients with known congenital heart defects
• Patients with severe emphysema, pulmonary vasculitis, or a history of pulmonary embolism
• Patients with respiratory distress syndrome
• Patients with a history of bleeding disorders
• Patients with bilirubin levels > 2 mg/dL

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group I (perflutren protein-type A microspheres, CEUS); Patients receive perflutren protein-type A microspheres IV over 10 minutes and undergo CEUS over 60 minutes at 1-6 hours and at approximately 7 and 14 days after yttrium Y-90 radioembolization.	Procedure: Dynamic Contrast-Enhanced Ultrasound Imaging; Undergo CEUS; Procedure: Yttrium-90 Microsphere Radioembolization; Undergo standard of care Y-90 radioembolization; Other Names: Yttrium Y 90 Microsphere Therapy; Yttrium-90 Radioembolization; Drug: Perflutren Protein-Type A Microspheres; Given IV.; Other Names: Optison
Active Comparator: Group II (standard of care); Patients undergo standard of care yttrium Y-90 radioembolization.	Procedure: Yttrium-90 Microsphere Radioembolization; Undergo standard of care Y-90 radioembolization; Other Names: Yttrium Y 90 Microsphere Therapy; Yttrium-90 Radioembolization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment response to yttrium Y-90 radioembolization	Measured using the modified Response Evaluation Criteria in Solid Tumors. Will be tested with a non-parametric Mann- Whitney U-test of the difference in response distributions between control (radioembolization alone) and experimental group (ultrasound-triggered microbubble destruction [UTMD] + radioembolization). The outcome variable in this analysis, the modified Response Evaluation Criteria in Solid Tumors (mRECIST) score, is treated as an ordinal variable in this analysis.	Up to 4 months
Tumor perfusion measured by contrast-enhanced ultrasound between ultrasound-triggered microbubble destruction pulses	Perfusion will be characterized in terms of contrast replenishment time intensity curves fit with a 2-parameter exponential recovery curve. The relationship between the normalized perfusion values from this image processing and the patients' subsequent mRECIST scores in the UTMD + radioembolization group will be evaluated with Spearman's rank order correlation.	Up to 14 days

Collaborators and Investigators

• Sponsor: Thomas Jefferson University
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH)
• Investigators: Principal Investigator: John Eisenbrey, PhD, Sidney Kimmel Cancer Center at Thomas Jefferson University

Publications and helpful links

Helpful Links

• Thomas Jefferson University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): February 27, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: June 22, 2017
• First Submitted That Met QC Criteria: June 22, 2017
• First Posted (Actual): June 26, 2017

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: 17F.222; 5R01CA238241 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No