Clinical trial NCT03295006: A TheraSphere® Advanced Dosimetry Retrospective Global Study in HCC
Official title: A TheraSphere® Advanced Dosimetry Retrospective Global Study Evaluation in Hepatocellular Carcinoma Treatment
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hepatocellular Carcinoma
Keywords: TheraSphere, hepatocellular carcinoma, dosimetry
Lead sponsor: Boston Scientific Corporation
Sponsor class: INDUSTRY
Collaborators: name: Biocompatibles UK Ltd
First posted: 2017-09-27
Enrollment: 209
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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

Eligibility criteria: 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).

Primary outcomes:
measure: Alternative two-compartment TheraSphere dosimetry methodology
timeFrame: Baseline
Secondary outcomes:
measure: Tumor dose
timeFrame: Baseline
measure: Serious adverse events
timeFrame: 3 months
measure: Specific non-serious adverse events (AEs) assessed as related or potentially related to the dose of TheraSphere
timeFrame: 3 months
measure: Clinical laboratory assessments
timeFrame: 6 weeks and 3 months
measure: Objective response (OR) of the target lesion and non-target sesions
timeFrame: 3 months and 6 months
measure: Volume changes
timeFrame: 3 and 6 months
measure: Overall Survival (OS)
timeFrame: 6 months
measure: Target Alpha fetoprotein (AFP) response
timeFrame: 6 weeks and 3 months
measure: Albumin-bilirubin (ALBI) score
timeFrame: 6 weeks and 3 months
measure: Dose to Portal Vein Thrombosis (PVT)
timeFrame: baseline, 90 days, 180 days
measure: Dosimetric analysis time
timeFrame: baseline
measure: Dose accuracy
timeFrame: baseline
measure: Dose reproducibility
timeFrame: baseline
Other outcomes:
measure: Normal tissue dose and tumor dose using post-procedural PET/CT Imaging
timeFrame: baseline
Locations:
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Chicago
country: United States
facility: Northwestern Memorial Hospital, Robert H Lurie Comprehensive Cancer Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine
state: Indiana
city: Saint Louis
country: United States
facility: Washington University in St. Louis, School of Medicine
state: Louisiana
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Rennes
country: France
facility: Centre Eugene Marquis
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Milan
country: Italy
facility: Foundation IRCCS Istituto Nazionale Tumori
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Riyad
country: Saudi Arabia
facility: King Faisal Hospital
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Fatih
country: Turkey
facility: Istanbul university Istanbul medical school
city: Şişli
country: Turkey
facility: Florence Nightingale
Study officials:
affiliation: Universitair Medisch Centrum Utrecht
name: Marnix Lam, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: Riad Salem, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Eugène Marquis
name: Etienne Garin, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Universitair Medisch Centrum Utrecht
name: Hugo de Jong, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.