Perflutren Protein-Type a Microspheres and Contrast-Enhanced Ultrasound in Improving Response to Radioembolization Therapy in Patients with Liver Cancer
- Conditions
- Hepatocellular Carcinoma
- Interventions
- Procedure: Yttrium-90 Microsphere RadioembolizationProcedure: Dynamic Contrast-Enhanced Ultrasound Imaging
- Registration Number
- NCT03199274
- Lead Sponsor
- Thomas Jefferson University
- 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
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 104
- 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
-
Females who are pregnant or nursing
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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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- 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 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Sidney Kimmel Cancer Center at Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States