Trial Information

A Prospective Randomized Open-labeled Trial Comparing RADIOEMBOLIZATION With Yttrium 90 Microspheres and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Background: In patients with advanced hepatocellular carcinoma, sorafenib is now the
standard treatment with an increased median overall survival but an overall incidence of
treatment-related adverse events of 80%. There is growing interest for RADIOEMBOLIZAION with
90 Yttrium microspheres. It involves infusion of embolic microparticles of glass or resin
impregnated with the isotope yttrium-90 through a catheter directly into the hepatic
arteries. A substantial number of open-label single-group studies showed supporting evidence
for a potential efficacy on overall survival and acceptable or low toxicity. Trial design:
multicenter, prospective, controlled, open label randomized trial of Y90 RADIOEMBOLIZATION
versus sorafenib. Participants: Adult patients with 1) advanced HCC according to BCLC
staging system (stage C) with or without portal vein thrombosis 2) ECOG performance status
of 2 or less 3) adequate haematological, renal and hepatic functions 4) liver cirrhosis
Child Pugh A - B7 and 5) no extrahepatic metastasis. Interventions: In the sorafenib
group, patients will receive continuous oral treatment with 400 mg of sorafenib twice daily.
In the Y90 RADIOEMBOLIZATION group, patients will first undergo angiography and scintigraphy
for eligibility assessment (absence of or acceptable lung shunting) and preconditioning
(embolization). RADIOEMBOLIZATION therapy with infusion of Y90 microspheres will be
performed secondly. Objectives: The primary objective is to compare the efficacy of Y90
RADIOEMBOLIZATION to sorafenib in the treatment of advanced hepatocellular carcinoma.
Secondary objectives include the comparison of safety profiles, quality of life and health
care costs between the two therapeutic groups. Outcomes: The primary endpoint is the
median overall survival time. Secondary endpoints include adverse events reported according
to the NCI CTC, progression-free survival at 6 months, response rates, general and
hepatic-specific quality of life scores, health care costs which comprise the MICROCOSTING
of Y90 RADIOEMBOLIZATION from the viewpoint of the hospital and the full cost of each
strategy. Sample size: 400 participants (200 par arm). The trial have 80% power to detect
a clinically meaningful increase in median survival time of 4 months between sorafenib
(expected median survival time 10.7 months) and Y90 RADIOEMBOLIZATION (expected median
survival time 15 months) with a two-tailed type I error risk of 5%. Randomization: 1 to
1 randomization will be stratified according to recruiting center, ECOG performance status
(a score of 0 vs. a score of 1 or 2), and the presence or absence of macroscopic vascular
invasion (obstruction of portal vein or any branch vs none). Randomly permuted blocks of
random sizes will be used. Study duration and Setting: Accrual period 24 months.
Additional follow-up period: 12 months. 14 centres involving both clinicians (hepatologists,
hepatobiliary surgeons, and oncologists) and radiologists and Nuclear medicine physicians on
each site.