Hepatocellular CarcinomaPhase 2NCT03199274
Perflutren Protein-Type A Microspheres and Contrast-Enhanced Ultrasound in Improving Response to Radioembolization Therapy in Patients With Liver Cancer
A Phase 2 study testing Yttrium-90 Microsphere Radioembolization, Perflutren Protein-Type A Microspheres and Dynamic Contrast-Enhanced Ultrasound Imaging in people with Hepatocellular Carcinoma, run by Thomas Jefferson University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatocellular Carcinoma
- What is being tested?
- Yttrium-90 Microsphere Radioembolization, Perflutren Protein-Type A Microspheres and Dynamic Contrast-Enhanced Ultrasound Imaging
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 104 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2017to 23 Jan 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 15Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Cancer Center at Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVE:
- Characterize the ability of localized ultrasound contrast agent destruction to improve hepatocellular carcinoma (HCC) response to yttrium Y-90 (Y90) radioembolization.
SECONDARY OBJECTIVE:
- 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.
- Conditions
- Hepatocellular Carcinoma
- Being tested
- Yttrium-90 Microsphere Radioembolization, Perflutren Protein-Type A Microspheres, Dynamic Contrast-Enhanced Ultrasound Imaging
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Yttrium-90 Microsphere RadioembolizationProcedure or surgery
Also called Yttrium Y 90 Microsphere Therapy, Yttrium-90 Radioembolization
Undergo standard of care Y-90 radioembolization
Perflutren Protein-Type A MicrospheresDrug
Also called Optison
Given IV.
Dynamic Contrast-Enhanced Ultrasound ImagingProcedure or surgery
Undergo CEUS
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Procedure: Yttrium-90 Microsphere Radioembolization |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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).
Measured: Up to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2017
- Study start1 Jul 2017
- Primary completion27 Feb 2024
- Study completion23 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatocellular CarcinomaStudies of the same condition, open and under way.
- More trials run by Thomas Jefferson UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 104 participants (actual)
Sponsor and investigators
- Lead sponsor
- Thomas Jefferson University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Principal investigator, john eisenbrey, Thomas Jefferson University
- Investigators
- John Eisenbrey, PhD, Principal investigator, Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03199274
- Sponsor's protocol ID
- 17F.222
- Other IDs
- 5R01CA238241, JT 10205
- Status last verified
- Dec 2025
- First submitted
- 22 Jun 2017
- Last updated
- 2 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 41025990
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ultrasound Microbubble Destruction and Perfusion Quantification for Improving Radioembolization Therapy of Hepatocellular Carcinoma
- ClinicalTrials.gov ID
- NCT03199274
- Acronym / sponsor ID
- 17F.222
- Conditions
- Hepatocellular Carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 104 participants (actual)
- Lead sponsor
- Thomas Jefferson UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- 27 Feb 2024 (actual)
- Study completion
- 23 Jan 2025 (actual)
- First posted
- 26 Jun 2017 (actual)
- Results
- Posted 20 Aug 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Characterize the ability of localized ultrasound contrast agent destruction to improve hepatocellular carcinoma (HCC) response to yttrium Y-90 (Y90) radioembolization.
SECONDARY OBJECTIVE:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group I (perflutren protein-type A microspheres, CEUS) | Experimental | Procedure: Yttrium-90 Microsphere Radioembolization, Drug: Perflutren Protein-Type A Microspheres, Procedure: Dynamic Contrast-Enhanced Ultrasound ImagingPatients 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) | Active comparator | Procedure: Yttrium-90 Microsphere RadioembolizationPatients undergo standard of care yttrium Y-90 radioembolization. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (15 listed)
- 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 with recent cerebral hemorrhage
- Patients with known sensitivities to albumin, blood, or blood products
- Patients with known hypersensitivity to perflutren
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Yttrium-90 Microsphere RadioembolizationAlso: Yttrium Y 90 Microsphere Therapy, Yttrium-90 RadioembolizationUndergo standard of care Y-90 radioembolization | Procedure or surgery | Group I (perflutren protein-type A microspheres, CEUS), Group II (standard of care) |
| Perflutren Protein-Type A MicrospheresAlso: OptisonGiven IV. | Drug | Group I (perflutren protein-type A microspheres, CEUS) |
| Dynamic Contrast-Enhanced Ultrasound ImagingUndergo CEUS | Procedure or surgery | Group I (perflutren protein-type A microspheres, CEUS) |
Primary outcome
Treatment Response to Yttrium Y-90 Radioembolization
Time frame: 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
Time frame: 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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41025990Wessner 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.
- Thomas Jefferson University HospitalLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John Eisenbrey, PhD principal investigator
Sidney Kimmel Comprehensive Cancer Center at Thomas Jefferson University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Yttrium-90 Microsphere Radioembolization, Perflutren Protein-Type A Microspheres and Dynamic Contrast-Enhanced Ultrasound Imaging in people with Hepatocellular Carcinoma, run by Thomas Jefferson University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Aug 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Response to Yttrium Y-90 Radioembolization (time frame: Up to 4 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03199274, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jan 2026.