Hepatocellular CarcinomaTARGETNCT03295006
A TheraSphere® Advanced Dosimetry Retrospective Global Study in HCC
An observational study of Hepatocellular Carcinoma, run by Boston Scientific Corporation at 14 sites in 8 countries.
Trial summary
This retrospective, multinational, single-arm study will be conducted in at least 8 sites. An interim analysis will be conducted with data from 100 patients with up to 10 well defined HCC tumor(s) and with at least one tumor ≥3 cm. 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?
- TheraSphere
- Type of treatment
- Medical device
- How many people
- 209 participants
- Where
- 14 sitesin 8 countries
- Study dates
- 31 Oct 2016to 1 Dec 2020
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: Patients with up to 10 well-defined unilobar HCC tumors per lobe with at least one tumor ≥3 cm ± PVT.
Who may be able to join
- Up to 10 well defined unilobar/bilobar HCC tumor(s) per lobe with at least one tumor ≥3 cm ± PVT
- Liver dominant disease (limited extra-hepatic metastases in the lung and/or lymph nodes are permitted (up to 5 lesions in the lung, with each individual lesion ≤2cm; any number of lymph node lesions with each individual lesion ≤2 cm).
- Child Pugh stage A or B7.
- BCLC A, B or C.
- Must be male or female, 18 years of age or older.
- Bilirubin ≤2 mg/dL.
Show all 13Show fewer
- Tumor replacement <50% of total liver volume assessed by diagnostic imaging consisting of multi-phase contrast enhanced CT or contrast enhanced MRI.
- Diagnostic imaging consisting of multi-phase contrast enhanced CT or contrast enhanced MRI within 3 months prior to TheraSphere® administration.
- Infusion of 99mTc-MAA in a single arterial location sufficient to cover up to 10 well-defined tumors per lobe ≤ 6 weeks prior to TheraSphere® administration.
- Patients must have received TheraSphere® in a single treatment setting in one or more arterial locations sufficient to cover up to 10 well-defined tumors based on angiography. Subsequent TheraSphere® treatment to the second lobe may occur at least 4 weeks following the initial TheraSphere® treatment.
- For patients receiving a second TheraSphere® treatment bilirubin levels must have been recorded prior to the second treatment
- Patients must have had clinical evaluation (assessment of liver specific AEs) and laboratory evaluation (at least a serum bilirubin level) at baseline.
- Tumor(s), ≥3 cm, measurable by mRECIST and RECIST 1.1 at baseline
Who cannot join
- Prior external beam radiation treatment to the liver.
- Prior loco-regional liver directed therapy (cTACE, DEB-TACE and SIR-Spheres).
- Prior liver transplantation.
- Whole liver TheraSphere® treatment following prior liver resection.
- TheraSphere administration to ≤2 segments (e.g., radiation segmentectomy).
- Additional active therapy (TACE and treatment with SIR-Spheres) between first TheraSphere treatment and 3 month (90 days) imaging.
- Hepatic vein invasion.
- Diagnosis of disease progression at peri-procedural imaging as compared to the baseline imaging (physician's discretion).
Trial locations and contacts
14 sites in 8 countries.
14 sites in 8 countries
United States6 sites
Northwestern Memorial Hospital, Robert H Lurie Comprehensive Cancer Center
Chicago, Illinois, 60611-2927
University of Florida College of Medicine
Gainesville, Florida, 32610-0374
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-3722
Indiana University School of Medicine
Indianapolis, Indiana, 46202
Washington University in St. Louis, School of Medicine
Saint Louis, Louisiana, 63110
Stanford University Medical Center
Stanford, California, 94305-5642
Turkey (Türkiye)2 sites
Istanbul university Istanbul medical school
Fatih, 34093
Florence Nightingale
Şişli, 34381
About this study
Official title: A TheraSphere® Advanced Dosimetry Retrospective Global Study Evaluation in Hepatocellular Carcinoma Treatment
This retrospective, multinational, single-arm study will be conducted in at least 8 sites. An interim analysis will be conducted with data from 100 patients with up to 10 well defined HCC tumor(s) and with at least one tumor ≥3 cm. Normal tissue absorbed dose using pre-procedural 99mTc MAA SPECT or SPECT/CT imaging will be measured to allow the mean absorbed normal tissue dose corresponding to a ≤15% probability of CTCAE grade 3 or higher hyperbilirubinemia (in the absence of disease progression) to be calculated. Total bilirubin will be recorded and graded according to CTCAE version 4.02. All dose-related SAEs at 3 months follow-up will be followed until resolution, death or lost-to-follow-up. AEs related to disease progression will not be considered related to TheraSphere.
Read the detailed description
Recently published evidence indicates a correlation between yttrium-90 dose delivered to the tumor and normal tissue with safety and efficacy outcomes but there are no validated methods to consistently measure dose delivered to the tumor and normal tissue. In contrast to the standard clinical approach based on average dose to one target volume, this trial, sponsored by Biocompatibles UK, will explore an alternative two-compartment TheraSphere dosimetry methodology to calculate absorbed dose to tumor and normal tissue
- Conditions
- Hepatocellular Carcinoma
- Being tested
- TheraSphere
- Keywords
- TheraSphere, hepatocellular carcinoma, dosimetry
- Medical subject headings
- Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TheraSphereDevice
Patients who had received TheraSphere
| Study group | Role | What they receive |
|---|---|---|
| Previous Therasphere treatment | Patients who had received TheraSphere yttrium-90 microspheres Receives: Device: TheraSphere |
What is being measured
The primary outcome is the main question the study is designed to answer.
Alternative two-compartment TheraSphere dosimetry methodology
Normal tissue absorbed dose using pre-procedural 99mTc MAA (Technetium-99m Macroaggregated albumin) SPECT (Single-photon emission computer tomography) or SPECT/CT (Single-photon emission computer tomography/Computer Tomography) imaging, to allow the mean absorbed normal tissue dose corresponding to a ≤15% probability of Common Toxicities Criteria for Adverse Events (CTCAE) grade 3 or higher hyperbilirubinemia (in the absence of disease progression) to be calculated.
Measured: Baseline
Secondary outcomes (13)
Tumor dose
Tumor dose (to tumors ≥3 cm) using pre-procedural 99mTc MAA SPECT or SPECT/CT imaging.
Measured: Baseline
Serious adverse events
All serious adverse events (SAEs) assessed as related or potentially related to TheraSphere
Measured: 3 months
Specific non-serious adverse events (AEs) assessed as related or potentially related to the dose of TheraSphere
Specific non-serious adverse events (AEs) assessed as related or potentially related to the dose of TheraSphere, comprising of any of the following events:
- Hyperbilirubinemia
- Ascites
- Pain
- Fatigue
- Nausea
Measured: 3 months
Clinical laboratory assessments
Clinical laboratory assessments
Measured: 6 weeks and 3 months
Objective response (OR) of the target lesion and non-target sesions
Objective response (OR) of the target lesion (single largest lesion) and non-target lesion(s) at 3 months and 6 months (if available), and for all scans up to 400 days after TheraSphere administration by Modified Response Evaluation Criteria in Solid Tumors (mRECIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Measured: 3 months and 6 months
Volume changes
Volume changes (i.e., perfused liver volume and non-perfused liver volume) from baseline afterTheraSphere administration.
Measured: 3 and 6 months
Overall Survival (OS)
Overall Survival (OS)
Measured: 6 months
Target Alpha fetoprotein (AFP) response
Target Alpha fetoprotein (AFP) response (defined as a ≥50% decrease in AFP levels for patients with a baseline AFP level of
≥200 ng/mL).
Measured: 6 weeks and 3 months
Albumin-bilirubin (ALBI) score
Albumin-bilirubin (ALBI) score, a measure of liver function for HCC patients after TheraSphere administration.
Measured: 6 weeks and 3 months
Dose to Portal Vein Thrombosis (PVT)
Dose to Portal Vein Thrombosis (PVT) based upon pre- and postprocedure imaging (if PVT present).
Measured: baseline, 90 days, 180 days
Dosimetric analysis time
Dosimetric analysis time (i.e., workflow).
Measured: baseline
Dose accuracy
Dose accuracy based upon phantom imaging studies.
Measured: baseline
Dose reproducibility
Measurement of inter-observer agreement based on a round robin review of the same 20 patients obtained from a minimum of 8 users (with each user at a different site) and an exploratory assessment of intra-observer agreement based on a review of 10 patients by a minimum of 8 users at least 2 weeks apart. The 10 patients for the intra-observer agreement will be a subset of the patients included in the assessment of inter-observer agreement.
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2017
- Study start31 Oct 2016
- Primary completion1 Dec 2020
- Study completion1 Dec 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)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 Boston Scientific CorporationThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 209 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston Scientific Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Biocompatibles UK Ltd
- Responsible party
- Sponsor
- Investigators
- Marnix Lam, MD, PhD, Principal investigator, Universitair Medisch Centrum UtrechtRiad Salem, MD, Principal investigator, Northwestern UniversityEtienne Garin, MD, Principal investigator, Centre Eugène MarquisHugo de Jong, PhD, Principal investigator, Universitair Medisch Centrum Utrecht
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03295006
- Sponsor's protocol ID
- BTG-007961
- Acronym
- TARGET
- Status last verified
- Apr 2021
- First submitted
- 29 Jun 2017
- Last updated
- 21 Apr 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Lam M, Garin E, Haste P, Denys A, Geller B, Kappadath SC, Turkmen C, Sze DY, Alsuhaibani HS, Herrmann K, Maccauro M, Cantasdemir M, Dreher M, Fowers KD, Gates V, Salem R. Utility of pre-procedural [99mTc]TcMAA SPECT/CT Multicompartment Dosimetry for Treatment Planning of 90Y Glass microspheres in patients with Hepatocellular Carcinoma: comparison of anatomic versus [99mTc]TcMAA-based Segmentation. Eur J Nucl Med Mol Imaging. 2025 Jan;52(2):744-755. doi: 10.1007/s00259-024-06920-6. Epub 2024 Sep 27.
PubMed 39331131Lam M, Garin E, Palard-Novello X, Mahvash A, Kappadath C, Haste P, Tann M, Herrmann K, Barbato F, Geller B, Schaefer N, Denys A, Dreher M, Fowers KD, Gates V, Salem R. Direct comparison and reproducibility of two segmentation methods for multicompartment dosimetry: round robin study on radioembolization treatment planning in hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2023 Dec;51(1):245-257. doi: 10.1007/s00259-023-06416-9. Epub 2023 Sep 12.
PubMed 37698645Lam M, Garin E, Maccauro M, Kappadath SC, Sze DY, Turkmen C, Cantasdemir M, Haste P, Herrmann K, Alsuhaibani HS, Dreher M, Fowers KD, Salem R. A global evaluation of advanced dosimetry in transarterial radioembolization of hepatocellular carcinoma with Yttrium-90: the TARGET study. Eur J Nucl Med Mol Imaging. 2022 Aug;49(10):3340-3352. doi: 10.1007/s00259-022-05774-0. Epub 2022 Apr 8.
PubMed 35394152
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A TheraSphere® Advanced Dosimetry Retrospective Global Study Evaluation in Hepatocellular Carcinoma Treatment
- ClinicalTrials.gov ID
- NCT03295006
- Acronym / sponsor ID
- TARGET / BTG-007961
- Conditions
- Hepatocellular Carcinoma
- Keywords
- TheraSphere, hepatocellular carcinoma, dosimetry
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 209 participants (actual)
- Lead sponsor
- Boston Scientific CorporationIndustry (pharma, biotech, devices)
- Collaborators
- Biocompatibles UK Ltd
- Study start
- 31 Oct 2016 (actual)
- Primary completion
- 1 Dec 2020 (actual)
- Study completion
- 1 Dec 2020 (actual)
- First posted
- 27 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This retrospective, multinational, single-arm study will be conducted in at least 8 sites. An interim analysis will be conducted with data from 100 patients with up to 10 well defined HCC tumor(s) and with at least one tumor ≥3 cm. Normal tissue absorbed dose using pre-procedural 99mTc MAA SPECT or SPECT/CT imaging will be measured to allow the mean absorbed normal tissue dose corresponding to a ≤15% probability of CTCAE grade 3 or higher hyperbilirubinemia (in the absence of disease progression) to be calculated. Total bilirubin will be recorded and graded according to CTCAE version 4.02. All dose-related SAEs at 3 months follow-up will be followed until resolution, death or lost-to-follow-up. AEs related to disease progression will not be considered related to TheraSphere.
Detailed description
Recently published evidence indicates a correlation between yttrium-90 dose delivered to the tumor and normal tissue with safety and efficacy outcomes but there are no validated methods to consistently measure dose delivered to the tumor and normal tissue. In contrast to the standard clinical approach based on average dose to one target volume, this trial, sponsored by Biocompatibles UK, will explore an alternative two-compartment TheraSphere dosimetry methodology to calculate absorbed dose to tumor and normal tissue
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Previous Therasphere treatment | – | Device: TheraSpherePatients who had received TheraSphere yttrium-90 microspheres |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with up to 10 well-defined unilobar HCC tumors per lobe with at least one tumor ≥3 cm ± PVT.
Key inclusion criteria (13 listed)
- Up to 10 well defined unilobar/bilobar HCC tumor(s) per lobe with at least one tumor ≥3 cm ± PVT
- Liver dominant disease (limited extra-hepatic metastases in the lung and/or lymph nodes are permitted (up to 5 lesions in the lung, with each individual lesion ≤2cm; any number of lymph node lesions with each individual lesion ≤2 cm).
- Child Pugh stage A or B7.
- BCLC A, B or C.
- Must be male or female, 18 years of age or older.
Key exclusion criteria (8 listed)
- Prior external beam radiation treatment to the liver.
- Prior loco-regional liver directed therapy (cTACE, DEB-TACE and SIR-Spheres).
- Prior liver transplantation.
- Whole liver TheraSphere® treatment following prior liver resection.
- TheraSphere administration to ≤2 segments (e.g., radiation segmentectomy).
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 |
|---|---|---|
| TheraSpherePatients who had received TheraSphere | Device | Previous Therasphere treatment |
Primary outcome
Alternative two-compartment TheraSphere dosimetry methodology
Time frame: Baseline
Normal tissue absorbed dose using pre-procedural 99mTc MAA (Technetium-99m Macroaggregated albumin) SPECT (Single-photon emission computer tomography) or SPECT/CT (Single-photon emission computer tomography/Computer Tomography) imaging, to allow the mean absorbed normal tissue dose corresponding to a ≤15% probability of Common Toxicities Criteria for Adverse Events (CTCAE) grade 3 or higher hyperbilirubinemia (in the absence of disease progression) to be calculated.
13 secondary outcomes
Tumor dose
Time frame: Baseline
Serious adverse events
Time frame: 3 months
Specific non-serious adverse events (AEs) assessed as related or potentially related to the dose of TheraSphere
Time frame: 3 months
Clinical laboratory assessments
Time frame: 6 weeks and 3 months
Objective response (OR) of the target lesion and non-target sesions
Time frame: 3 months and 6 months
Volume changes
Time frame: 3 and 6 months
Overall Survival (OS)
Time frame: 6 months
Target Alpha fetoprotein (AFP) response
Time frame: 6 weeks and 3 months
Albumin-bilirubin (ALBI) score
Time frame: 6 weeks and 3 months
Dose to Portal Vein Thrombosis (PVT)
Time frame: baseline, 90 days, 180 days
Dosimetric analysis time
Time frame: baseline
Dose accuracy
Time frame: baseline
Dose reproducibility
Time frame: baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2021.
- Derived from this study: PubMed 39331131Lam M, Garin E, Haste P, Denys A, Geller B, Kappadath SC, Turkmen C, Sze DY, Alsuhaibani HS, Herrmann K, Maccauro M, Cantasdemir M, Dreher M, Fowers KD, Gates V, Salem R. Utility of pre-procedural [99mTc]TcMAA SPECT/CT Multicompartment Dosimetry for Treatment Planning of 90Y Glass microspheres in patients with Hepatocellular Carcinoma: comparison of anatomic versus [99mTc]TcMAA-based Segmentation. Eur J Nucl Med Mol Imaging. 2025 Jan;52(2):744-755. doi: 10.1007/s00259-024-06920-6. Epub 2024 Sep 27.
- Derived from this study: PubMed 37698645Lam M, Garin E, Palard-Novello X, Mahvash A, Kappadath C, Haste P, Tann M, Herrmann K, Barbato F, Geller B, Schaefer N, Denys A, Dreher M, Fowers KD, Gates V, Salem R. Direct comparison and reproducibility of two segmentation methods for multicompartment dosimetry: round robin study on radioembolization treatment planning in hepatocellular carcinoma. Eur J Nucl Med Mol Imaging. 2023 Dec;51(1):245-257. doi: 10.1007/s00259-023-06416-9. Epub 2023 Sep 12.
- Derived from this study: PubMed 35394152Lam M, Garin E, Maccauro M, Kappadath SC, Sze DY, Turkmen C, Cantasdemir M, Haste P, Herrmann K, Alsuhaibani HS, Dreher M, Fowers KD, Salem R. A global evaluation of advanced dosimetry in transarterial radioembolization of hepatocellular carcinoma with Yttrium-90: the TARGET study. Eur J Nucl Med Mol Imaging. 2022 Aug;49(10):3340-3352. doi: 10.1007/s00259-022-05774-0. Epub 2022 Apr 8.
- 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.
Marnix Lam, MD, PhD principal investigator
Universitair Medisch Centrum Utrecht
Riad Salem, MD principal investigator
Northwestern University
Etienne Garin, MD principal investigator
Centre Eugène Marquis
14 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatocellular Carcinoma, run by Boston Scientific Corporation at 14 sites in 8 countries.
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 13 inclusion and 8 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 21 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Turkey (Türkiye), France, Germany, Italy and 3 more countries. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Alternative two-compartment TheraSphere dosimetry methodology (time frame: Baseline). 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 NCT03295006, which also lists 3 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 21 Apr 2021.