A TheraSphere® Advanced Dosimetry Retrospective Global Study in HCC (TARGET)

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.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Device: 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 Type: Observational
• Enrollment (Actual): 209

Contacts and Locations

Study Locations

• France
  • Rennes, France, 44229
    • Centre Eugène Marquis
• Germany
  • Essen, Germany, 45122
    • Universitätsklinikum Essen
• Italy
  • Milan, Italy, 20133
    • Foundation IRCCS Istituto Nazionale Tumori
• Netherlands
  • Utrecht, Netherlands, 3509 GA
    • Universitair Medisch Centrum Utrecht
• Saudi Arabia
  • Riyad, Saudi Arabia, 12713
    • King Faisal Hospital
• Switzerland
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois
• Turkey
  • Fatih, Turkey, 34093
    • Istanbul University Istanbul Medical School
  • Şişli, Turkey, 34381
    • Florence Nightingale
• United States
  • California
    • Stanford, California, United States, 94305-5642
      • Stanford University Medical Center
  • Florida
    • Gainesville, Florida, United States, 32610-0374
      • University of Florida College of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60611-2927
      • Northwestern Memorial Hospital, Robert H Lurie Comprehensive Cancer Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Louisiana
    • Saint Louis, Louisiana, United States, 63110
      • Washington University in St. Louis, School of Medicine
  • Texas
    • Houston, Texas, United States, 77030-3722
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with up to 10 well-defined unilobar HCC tumors per lobe with at least one tumor ≥3 cm ± PVT.

Description

Inclusion Criteria:

• 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.
• 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

Exclusion Criteria:

• 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).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Previous Therasphere treatment; Patients who had received TheraSphere yttrium-90 microspheres	Device: TheraSphere; Patients who had received TheraSphere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor dose	Tumor dose (to tumors ≥3 cm) using pre-procedural 99mTc MAA SPECT or SPECT/CT imaging.	Baseline
Serious adverse events	All serious adverse events (SAEs) assessed as related or potentially related to TheraSphere	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	3 months
Clinical laboratory assessments	Clinical laboratory assessments	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	3 months and 6 months
Volume changes	Volume changes (i.e., perfused liver volume and non-perfused liver volume) from baseline afterTheraSphere administration.	3 and 6 months
Overall Survival (OS)	Overall Survival (OS)	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).	6 weeks and 3 months
Albumin-bilirubin (ALBI) score	Albumin-bilirubin (ALBI) score, a measure of liver function for HCC patients after TheraSphere administration.	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).	baseline, 90 days, 180 days
Dosimetric analysis time	Dosimetric analysis time (i.e., workflow).	baseline
Dose accuracy	Dose accuracy based upon phantom imaging studies.	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.	baseline

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normal tissue dose and tumor dose using post-procedural PET/CT Imaging	Normal tissue dose and tumor dose (in tumors ≥3 cm) using post-procedural yttrium-90 Positron Emission Tomography/Computed Tomography (PET/CT) imaging; collection of these endpoints will allow an assessment of the correlation with the dose determined from preprocedural 99mTc MAA SPECT or SPECT/CT imaging.	baseline

Collaborators and Investigators

• Sponsor: Boston Scientific Corporation
• Collaborators: Biocompatibles UK Ltd
• Investigators: Principal Investigator: Marnix Lam, MD, PhD, Universitair Medisch Centrum Utrecht; Principal Investigator: Etienne Garin, MD, Centre Eugène Marquis; Principal Investigator: Hugo de Jong, PhD, Universitair Medisch Centrum Utrecht

Publications and helpful links

General Publications

• Lam 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.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2016
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: June 29, 2017
• First Submitted That Met QC Criteria: September 22, 2017
• First Posted (Actual): September 27, 2017

Study Record Updates

• Last Update Posted (Actual): April 21, 2021
• Last Update Submitted That Met QC Criteria: April 19, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: TheraSphere, hepatocellular carcinoma, dosimetry
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: BTG-007961

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No