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

Phase 3
18 Years
Open (Enrolling)
Liver Carcinoma

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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.

Inclusion Criteria:

- Histological or cytological diagnosis or meet the AASLD criteria for diagnosis of HCC
and at least one uni-dimensional lesion measurable according to RECIST criteria by
CT-scan or MRI

- Adult over 18 years old and estimated life expectancy over 3 months

- Patient with advanced HCC according to BCLC staging system (stage C) with or without
portal vein thrombosis, not eligible for surgical resection, liver transplantation
nor radiofrequency ablation OR patient with progression or recurrence of HCC after
surgical or locoregional treatment not eligible for surgical resection, liver
transplantation nor radiofrequency ablation.

- ECOG performance status under or equals 1

- Adequate haematological function: Hb over or equals 9g/100mL, absolute neutrophil
count over or equals 1 500/mm3, platelet count over or equals 50 000/mm3

- Adequate renal function; serum creatinine under 150μmol/L

- Bilirubin under or equals 50 µmol/L, AST or ALT uner or equals 5 x ULN, INR under or
equals 1.5

- Liver cirrhosis Child Pugh A - B7

- written informed consent

Exclusion Criteria:

- Another primary tumour, with the exception of conventional basal cell carcinoma or
superficial bladder neoplasia

- Extrahepatic metastasis

- Advanced HCC previously treated

- Advanced liver disease with Child-Pugh score over 7 or active gastrointestinal
bleeding or encephalopathy or ascites refractory to diuretic therapy Women who are
pregnant or breast feeding

- Allergy to contrast media

- Contraindication to hepatic artery catheterisation, such as severe peripheral
vascular disease precluding catheterisation

- Psychiatric or other disorder likely to impact on informed consent

- Patient unable and/or unwilling to comply with treatment and study instructions

- Patient unable to swallow oral medications

Type of Study:


Study Design:

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Median overall survival time

Outcome Description:

Median overall survival time since randomisation

Outcome Time Frame:

36 months

Safety Issue:


Principal Investigator

Valerie Vilgrain, PD, PhD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Department of radiology


France: Committee for the Protection of Personnes

Study ID:




Start Date:

December 2011

Completion Date:

December 2015

Related Keywords:

  • Liver Carcinoma
  • Liver, HCC
  • Liver, interventional procedures
  • Liver, randomized studies
  • Liver, targeted therapy
  • Carcinoma
  • Carcinoma, Hepatocellular