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

Phase 2

Active, not recruiting

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

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.

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Group I (perflutren protein-type A microspheres, CEUS)	Perflutren Protein-Type A Microspheres	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.
Group I (perflutren protein-type A microspheres, CEUS)	Yttrium-90 Microsphere Radioembolization	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.
Group I (perflutren protein-type A microspheres, CEUS)	Dynamic Contrast-Enhanced Ultrasound Imaging	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.
Group II (standard of care)	Yttrium-90 Microsphere Radioembolization	Patients undergo standard of care yttrium Y-90 radioembolization.

Primary Outcome Measures

Name	Time	Method
Treatment Response to Yttrium Y-90 Radioembolization	Up to 4 months	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)
Tumor Perfusion Measured by Contrast-enhanced Ultrasound Between Ultrasound-triggered Microbubble Destruction Pulses	Up to 14 days	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).

Secondary Outcome Measures

Name	Time	Method

Locations (1): Sidney Kimmel Cancer Center at Thomas Jefferson University
🇺🇸
Philadelphia, Pennsylvania, United States
Sidney Kimmel Cancer Center at Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States