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

NCT03199274 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: 17F.2225R01CA238241JT 10205
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• 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. Tumor response assessed using modified Response Evaluation Criteria in Solid Tumors (mRECIST). The mRECIST scale includes four ordered categories: * Complete Response (best outcome) * Partial Response * Stable Disease * Progressive Disease (worst outcome)

  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. Tumor perfusion measured as fractional vascularity (%) using contrast-enhanced ultrasound (CEUS). Values range from 0% (no perfusion) to 100% (maximal perfusion).

  Up to 14 days

Study Arms (2)

Group I (perflutren protein-type A microspheres, CEUS)

EXPERIMENTAL

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: Yttrium-90 Microsphere Radioembolization; Drug: Perflutren Protein-Type A Microspheres; Procedure: Dynamic Contrast-Enhanced Ultrasound Imaging

Group II (standard of care)

ACTIVE COMPARATOR

Patients undergo standard of care yttrium Y-90 radioembolization.

Procedure: Yttrium-90 Microsphere Radioembolization

Interventions

Yttrium-90 Microsphere Radioembolization PROCEDURE

Undergo standard of care Y-90 radioembolization

Also known as: Yttrium Y 90 Microsphere Therapy, Yttrium-90 Radioembolization

Group I (perflutren protein-type A microspheres, CEUS); Group II (standard of care)

Perflutren Protein-Type A Microspheres DRUG

Given IV.

Also known as: Optison

Group I (perflutren protein-type A microspheres, CEUS)

Dynamic Contrast-Enhanced Ultrasound Imaging PROCEDURE

Undergo CEUS

Group I (perflutren protein-type A microspheres, CEUS)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Thomas Jefferson University: lead
• National Institutes of Health (NIH): collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Sidney Kimmel Cancer Center at Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

Related Publications (1)

• Wessner CE, Forsberg F, Lyshchik A, O'Kane P, Bradigan K, Liu JB, Delaney LJ, Anton K, Topper SR, Civan J, Maley W, Keith SW, Shaw CM, Eisenbrey JR. Microbubble-based Radiosensitization of Hepatocellular Carcinoma: Evaluation of Safety and Efficacy in a Phase II Randomized Trial. Radiology. 2025 Sep;316(3):e250083. doi: 10.1148/radiol.250083.

  PMID: 41025990 DERIVED

Related Links

• Thomas Jefferson University Hospital

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

FS 069

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Results Point of Contact

• Title: John Eisenbrey, PhD
• Organization: Thomas Jefferson University

john.eisenbrey@jefferson.edu

(215) 503-5188

Study Officials

• John Eisenbrey, PhD

  Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Radiology

Study Record Dates

• First Submitted: June 22, 2017
• First Posted: June 26, 2017
• Study Start: July 1, 2017
• Primary Completion: February 27, 2024
• Study Completion: January 23, 2025
• Last Updated: January 2, 2026
• Results First Posted: August 20, 2025

Record last verified: 2025-12

Locations

US (1)