Hepatocellular Carcinoma
Conditions
Keywords
TheraSphere, hepatocellular carcinoma, dosimetry
Brief 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.
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
Interventions
DEVICETheraSphere
Patients who had received TheraSphere
Sponsors
Biocompatibles UK Ltd
Boston Scientific Corporation
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Alternative two-compartment TheraSphere dosimetry methodology | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Dose reproducibility | baseline | 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. |
| Tumor dose | Baseline | Tumor dose (to tumors ≥3 cm) using pre-procedural 99mTc MAA SPECT or SPECT/CT imaging. |
| Serious adverse events | 3 months | All serious adverse events (SAEs) assessed as related or potentially related to TheraSphere |
| Specific non-serious adverse events (AEs) assessed as related or potentially related to the dose of TheraSphere | 3 months | 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 |
| Clinical laboratory assessments | 6 weeks and 3 months | Clinical laboratory assessments |
| Objective response (OR) of the target lesion and non-target sesions | 3 months and 6 months | 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 |
| Overall Survival (OS) | 6 months | Overall Survival (OS) |
| Target Alpha fetoprotein (AFP) response | 6 weeks and 3 months | Target Alpha fetoprotein (AFP) response (defined as a ≥50% decrease in AFP levels for patients with a baseline AFP level of ≥200 ng/mL). |
| Albumin-bilirubin (ALBI) score | 6 weeks and 3 months | Albumin-bilirubin (ALBI) score, a measure of liver function for HCC patients after TheraSphere administration. |
| Dose to Portal Vein Thrombosis (PVT) | baseline, 90 days, 180 days | Dose to Portal Vein Thrombosis (PVT) based upon pre- and postprocedure imaging (if PVT present). |
| Dosimetric analysis time | baseline | Dosimetric analysis time (i.e., workflow). |
| Dose accuracy | baseline | Dose accuracy based upon phantom imaging studies. |
| Volume changes | 3 and 6 months | Volume changes (i.e., perfused liver volume and non-perfused liver volume) from baseline afterTheraSphere administration. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Normal tissue dose and tumor dose using post-procedural PET/CT Imaging | baseline | 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. |
Countries
France, Germany, Italy, Netherlands, Saudi Arabia, Switzerland, Turkey (Türkiye), United States
Outcome results
None listed