A TheraSphere® Advanced Dosimetry Retrospective Global Study in HCC

Hepatocellular Carcinoma Clinical Trial

— TARGET  

Official title:

A TheraSphere® Advanced Dosimetry Retrospective Global Study Evaluation in Hepatocellular Carcinoma Treatment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03295006
• Other study ID #: BTG-007961
• Status: Completed
• Start date: October 31, 2016
• Est. completion date: December 1, 2020

Study information

• Verified date: April 2021
• Source: Boston Scientific Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 209
• Est. completion date: December 1, 2020
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• Hepatocellular Carcinoma

Intervention

Device:
• TheraSphere
Patients who had received TheraSphere

Locations

Country	Name	City	State
France	Centre Eugene Marquis	Rennes
Germany	Universitätsklinikum Essen	Essen
Italy	Foundation IRCCS Istituto Nazionale Tumori	Milan
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
Saudi Arabia	King Faisal Hospital	Riyad
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Turkey	Istanbul university Istanbul medical school	Fatih
Turkey	Florence Nightingale	Sisli
United States	Northwestern Memorial Hospital, Robert H Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	University of Florida College of Medicine	Gainesville	Florida
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Washington University in St. Louis, School of Medicine	Saint Louis	Louisiana
United States	Stanford University Medical Center	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Boston Scientific Corporation	Biocompatibles UK Ltd

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Netherlands,  Saudi Arabia,  Switzerland,  Turkey, 

Outcome

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