HCCNCT04172714
Low-dose Y90 Treatment Planning for HCC
A study testing SIR-Spheres microspheres in people with HCC and Cancer of Liver, run by Emory University at 3 sites in United States.
Trial summary
The study proposes low-dose Y90 microspheres for therapy planning of HCC, as an alternative to Technetium (99mTc) albumin aggregated (MAA), to be a bioidentical therapeutic Y90 surrogate marker to better predict and thus achieve optimal therapeutic dosing. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HCC, Cancer of Liver, Cancer
- What is being tested?
- SIR-Spheres microspheres
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesUnited States
- Study dates
- 16 Dec 2019to 30 Jun 2021
- Phase
- Interventional
- 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
- Adults ≥ 18 years
- Life expectancy of 6 months or more as determined by the investigator
- HCC confirmed by Liver Reporting \& Data System (LIRADS) on MRI or CT
- Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) with CT scan, MRI, or calipers by clinical exam. See Section 12 (Measurement of Effect) for the evaluation of measurable disease.
- ≤3 lesions
- Longest dimension of the largest lesion ≤7cm
Show all 20Show fewer
- Single lobe disease
- No significant extrahepatic metastatic disease
- Barcelona Clinic Liver Cancer Stage A, B or C
- ECOG < 2 (Appendix A)
- Lesion(s) <50% of liver volume
- Bilirubin ≤ 2 mg/dL
- Albumin ≥ 3 g/dL
- PT/INR < 2
- AST/ALT ≤ 3 institutional upper limit of normal (ULN)
- Platelet count > 50,000/mcL
- Lung shunt fraction of <20% by planar MAA if dose modification results in inadequate dose delivered to the tumor(s)
- Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥ 12 week before the start of study therapy. Willingness and ability of the subject to comply with scheduled visits, drug administration plan, protocol-specified laboratory tests, other study procedures, and study restrictions.
- Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation. v. The effects of Y90 microspheres on the developing human fetus are unknown. For this reason female of child-bearing potential (FCBP) must have a negative serum or urine pregnancy test prior to starting therapy. Winship Protocol #: RAD4784 Version Date: Aug 22, 2019 20 | P a g e w. FCBP and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of [IND Agent] administration. A female of childbearing potential (FCBP) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months
Who cannot join
- An individual who does not meet all the inclusion criteria in section.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Emory University Midtown
Atlanta, Georgia, 30308
Emory Clinic
Atlanta, Georgia, 30322
Emory University Hospital
Atlanta, Georgia, 30322
About this study
Official title: Theragnostic Low Dose Y90 Microspheres for Personalized Y90 Radioembolization Dosimetry Planning
The study proposes low-dose Y90 microspheres for therapy planning of HCC, as an alternative to Technetium (99mTc) albumin aggregated (MAA), to be a bioidentical therapeutic Y90 surrogate marker to better predict and thus achieve optimal therapeutic dosing.
Read the detailed description
Hepatocellular carcinoma is a second deadliest cancer in the world with less than 20% of patients eligible for curative surgery at the time of diagnosis. Yttrium-90 (Y90) radioembolization is palliative treatment with promising result. However, one of the most important factors in the success of Y90 treatment is to ensure adequate dose of radioactive material is delivered to the tumor. The technetium-99 macroaggregated albumin (MAA) which is currently used for Y90 treatment planning and shunt study does not predict distribution of Y90 in the lungs, tumors, and liver. Therefore, accurate and personalized treatment planning cannot be performed using MAA. In this study, we are proposing using low-dose Y90 microspheres for the planning stage of the therapy to obtain an accurate estimation of distribution of Y90 therapy dose. This will in turn allow us to ensure adequate dose of Y90 is delivered to the tumor(s) while minimizing dose delivered to non-tumor liver and lungs in order to decrease the chance of treatment related toxicity to the liver and lungs.
- Conditions
- HCC, Cancer of Liver, Cancer
- Being tested
- SIR-Spheres microspheres
- Keywords
- Cancer, Radiation therapy, Liver Diseases, Radiology, Interventional, Radiology
- Medical subject headings
- Liver Neoplasms, Neoplasms, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SIR-Spheres microspheresDevice
Also called SIRSPHERE, Y90 resin-based microspheres
SIR-Spheres® Y-90 resin microspheres consist of biocompatible polymer resin microspheres of a median diameter of 32.5 microns (range between 20 and 60 microns) loaded with yttrium-90 (beta radiation penetrating an average of 2.5 mm in tissue to destroy tumor cells). The resin microspheres are small enough to become lodged in the arterioles within the growing rim of the tumor but are too large to pass through the capillaries and into the venous system. Since yttrium-90 has a half-life of 64.1 hours, most of the radiation (94%) is delivered to the tumor over 11 days.
| Study group | Role | What they receive |
|---|---|---|
| Second mapping with low-dose Y90 | Experimental | Patients will undergo standard of care mapping study with 99TC-MAA to plan for Y90 radioembolization therapy. Additionally,non-standard of care, intervention will be to do a second mapping study using SIR-spheres microspheres with low-dose Y90 (15 mCi) before the therapeutic Y90 radioembolization. Receives: Device: SIR-Spheres microspheres |
What is being measured
The primary outcome is the main question the study is designed to answer.
Lung Shunt Fraction (LSF) Ratio
Y-90 radioembolization treatment requires estimating the activity shunted from the liver to the lungs, referred to as a lung shunt fraction (LSF). It is expressed in ratios, with higher ratio meaning a higher transit of Y-90 to the lungs (worse outcome) and lower ratio, lower transit of Y-90 to the lungs (better outcome).
Measured: Baseline
Tumor to Normal Liver Activity Ratio (TNR)
The ratios of the tumor-to-normal liver parenchymal radioactivity uptake count will be measured. TNR values will be calculated by dividing the mean count of the tumorous volume of interest (VOI) by the mean count of normal liver.
Measured: Baseline
Secondary outcomes (1)
Number of Participants With Tumor Response Using Imaging Modified Response Criteria in Solid Tumors (m-RECIST) Post Y90 Embolization
To identify tumor dose response threshold (TDRT) using Imaging Modified Response Criteria in Solid Tumors (m-RECIST), that is a method for measuring treatment response and measure of antitumor activity of cytotoxic drugs. This is measured using imaging: CT or MRI. The overall response is a combination of responses in each category: complete response (disappearance of any intramural arterial enhancement in all target lesions), partial response (at least 30% decrease in the sum of the diameters of viable target lesions), stable disease (any cases that do not qualify for either partial response or progressive disease) or progressive disease (an increase of at least 20% in the sum of the diameters of viable, enhancing target lesions, taking as a reference the smallest sum of the diameters of viable target lesions recorded since treatment started).
Measured: 6 months post intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2019
- Study start16 Dec 2019
- Primary completion30 Jun 2021
- Study completion30 Jun 2021
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 (4)Papers the sponsor has linked to this study.
- Other trials for HCCStudies of the same condition, open and under way.
- More trials run by Emory 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nima Kokabi, Emory University
- Investigators
- Nima Kokabi, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04172714
- Sponsor's protocol ID
- IRB00112192
- Status last verified
- Nov 2022
- First submitted
- 20 Nov 2019
- Last updated
- 6 Dec 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Shahbazian H, Du Pisane JL, Brandon D, Galt JR, Kappadath SC, Schuster DM, Xing M, Afrasiabi A, Gad S, Kokabi N. Quantitative Comparison of Yettirium-90 (Y90) PET/CT and Y90 SPECT/CT Voxel-Based Dosimetry post Resin Y90 Microsphere Radioembolization. Cardiovasc Intervent Radiol. 2026 Sep 24. doi: 10.1007/s00270-026-04620-2. Online ahead of print.
PubMed 42786295Kokabi N, Webster LA, Dabbous H, Shah A, Brandon D, Galt J, Xing M, Villalobos A, Davarpanahfakhr A, Kappadath SC, Schuster DM. Resin-Based 90 Y Tumor Dose as a Predictor of Duration of Response and Survival in Patients With Surgically Unresectable Hepatocellular Carcinoma : A Prospective Single-Arm Study. Clin Nucl Med. 2024 Sep 1;49(9):799-805. doi: 10.1097/RLU.0000000000005198. Epub 2024 May 21.
PubMed 38861361Kokabi N, Arndt-Webster L, Chen B, Brandon D, Sethi I, Davarpanahfakhr A, Galt J, Elsayed M, Bercu Z, Cristescu M, Kappadath SC, Schuster DM. Voxel-based dosimetry predicting treatment response and related toxicity in HCC patients treated with resin-based Y90 radioembolization: a prospective, single-arm study. Eur J Nucl Med Mol Imaging. 2023 May;50(6):1743-1752. doi: 10.1007/s00259-023-06111-9. Epub 2023 Jan 18.
PubMed 36650357Kokabi N, Webster LA, Elsayed M, Switchenko JM, Chen B, Brandon D, Galt J, Sethi I, Cristescu M, Kappadath SC, Schuster DM. Accuracy and Safety of Scout Dose Resin Yttrium-90 Microspheres for Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial. J Vasc Interv Radiol. 2022 Dec;33(12):1578-1587.e5. doi: 10.1016/j.jvir.2022.08.027. Epub 2022 Sep 6.
PubMed 36075560
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Theragnostic Low Dose Y90 Microspheres for Personalized Y90 Radioembolization Dosimetry Planning
- ClinicalTrials.gov ID
- NCT04172714
- Acronym / sponsor ID
- IRB00112192
- Conditions
- HCC, Cancer of Liver, Cancer
- Keywords
- Cancer, Radiation therapy, Liver Diseases, Radiology, Interventional, Radiology
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- 16 Dec 2019 (actual)
- Primary completion
- 30 Jun 2021 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 21 Nov 2019 (actual)
- Results
- Posted 6 Dec 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study proposes low-dose Y90 microspheres for therapy planning of HCC, as an alternative to Technetium (99mTc) albumin aggregated (MAA), to be a bioidentical therapeutic Y90 surrogate marker to better predict and thus achieve optimal therapeutic dosing.
Detailed description
Hepatocellular carcinoma is a second deadliest cancer in the world with less than 20% of patients eligible for curative surgery at the time of diagnosis. Yttrium-90 (Y90) radioembolization is palliative treatment with promising result. However, one of the most important factors in the success of Y90 treatment is to ensure adequate dose of radioactive material is delivered to the tumor. The technetium-99 macroaggregated albumin (MAA) which is currently used for Y90 treatment planning and shunt study does not predict distribution of Y90 in the lungs, tumors, and liver. Therefore, accurate and personalized treatment planning cannot be performed using MAA. In this study, we are proposing using low-dose Y90 microspheres for the planning stage of the therapy to obtain an accurate estimation of distribution of Y90 therapy dose. This will in turn allow us to ensure adequate dose of Y90 is delivered to the tumor(s) while minimizing dose delivered to non-tumor liver and lungs in order to decrease the chance of treatment related toxicity to the liver and lungs.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Second mapping with low-dose Y90 | Experimental | Device: SIR-Spheres microspheresPatients will undergo standard of care mapping study with 99TC-MAA to plan for Y90 radioembolization therapy. Additionally,non-standard of care, intervention will be to do a second mapping study using SIR-spheres microspheres with low-dose Y90 (15 mCi) before the therapeutic Y90 radioembolization. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Adults ≥ 18 years
- Life expectancy of 6 months or more as determined by the investigator
- HCC confirmed by Liver Reporting \& Data System (LIRADS) on MRI or CT
- Must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) with CT scan, MRI, or calipers by clinical exam. See Section 12 (Measurement of Effect) for the evaluation of measurable disease.
- ≤3 lesions
Key exclusion criteria (1 listed)
- An individual who does not meet all the inclusion criteria in section.
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 |
|---|---|---|
| SIR-Spheres microspheresAlso: SIRSPHERE, Y90 resin-based microspheresSIR-Spheres® Y-90 resin microspheres consist of biocompatible polymer resin microspheres of a median diameter of 32.5 microns (range between 20 and 60 microns) loaded with yttrium-90 (beta radiation penetrating an average of 2.5 mm in tissue to destroy tumor cells). The resin microspheres are small enough to become lodged in the arterioles within the growing rim of the tumor but are too large to pass through the capillaries and into the venous system. Since yttrium-90 has a half-life of 64.1 hours, most of the radiation (94%) is delivered to the tumor over 11 days. | Device | Second mapping with low-dose Y90 |
Primary outcome
Lung Shunt Fraction (LSF) Ratio
Time frame: Baseline
Y-90 radioembolization treatment requires estimating the activity shunted from the liver to the lungs, referred to as a lung shunt fraction (LSF). It is expressed in ratios, with higher ratio meaning a higher transit of Y-90 to the lungs (worse outcome) and lower ratio, lower transit of Y-90 to the lungs (better outcome).
Tumor to Normal Liver Activity Ratio (TNR)
Time frame: Baseline
The ratios of the tumor-to-normal liver parenchymal radioactivity uptake count will be measured. TNR values will be calculated by dividing the mean count of the tumorous volume of interest (VOI) by the mean count of normal liver.
1 secondary outcome
Number of Participants With Tumor Response Using Imaging Modified Response Criteria in Solid Tumors (m-RECIST) Post Y90 Embolization
Time frame: 6 months post intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42786295Shahbazian H, Du Pisane JL, Brandon D, Galt JR, Kappadath SC, Schuster DM, Xing M, Afrasiabi A, Gad S, Kokabi N. Quantitative Comparison of Yettirium-90 (Y90) PET/CT and Y90 SPECT/CT Voxel-Based Dosimetry post Resin Y90 Microsphere Radioembolization. Cardiovasc Intervent Radiol. 2026 Sep 24. doi: 10.1007/s00270-026-04620-2. Online ahead of print.
- Derived from this study: PubMed 38861361Kokabi N, Webster LA, Dabbous H, Shah A, Brandon D, Galt J, Xing M, Villalobos A, Davarpanahfakhr A, Kappadath SC, Schuster DM. Resin-Based 90 Y Tumor Dose as a Predictor of Duration of Response and Survival in Patients With Surgically Unresectable Hepatocellular Carcinoma : A Prospective Single-Arm Study. Clin Nucl Med. 2024 Sep 1;49(9):799-805. doi: 10.1097/RLU.0000000000005198. Epub 2024 May 21.
- Derived from this study: PubMed 36650357Kokabi N, Arndt-Webster L, Chen B, Brandon D, Sethi I, Davarpanahfakhr A, Galt J, Elsayed M, Bercu Z, Cristescu M, Kappadath SC, Schuster DM. Voxel-based dosimetry predicting treatment response and related toxicity in HCC patients treated with resin-based Y90 radioembolization: a prospective, single-arm study. Eur J Nucl Med Mol Imaging. 2023 May;50(6):1743-1752. doi: 10.1007/s00259-023-06111-9. Epub 2023 Jan 18.
- Derived from this study: PubMed 36075560Kokabi N, Webster LA, Elsayed M, Switchenko JM, Chen B, Brandon D, Galt J, Sethi I, Cristescu M, Kappadath SC, Schuster DM. Accuracy and Safety of Scout Dose Resin Yttrium-90 Microspheres for Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial. J Vasc Interv Radiol. 2022 Dec;33(12):1578-1587.e5. doi: 10.1016/j.jvir.2022.08.027. Epub 2022 Sep 6.
- Individual participant dataSharing planned: No
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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.
Nima Kokabi, MD principal investigator
Emory University
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SIR-Spheres microspheres in people with HCC and Cancer of Liver, run by Emory University at 3 sites 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 20 inclusion and 1 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 6 Dec 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Dec 2022). 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?
Lung Shunt Fraction (LSF) Ratio (time frame: Baseline). 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 NCT04172714, which also lists 4 linked publications.
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 6 Dec 2022.