SorAfenib Versus RADIOEMBOLIZATION in Advanced Hepatocellular Carcinoma
- Registration Number
- NCT01482442
- Lead Sponsor
- Assistance Publique - H么pitaux de Paris
- Brief Summary
The purpose of this study is to determine whether RADIOEMBOLIZATION with 90 Yttrium microspheres is more effective on overall survival in advanced Hepatocellular carcinoma (HCC) with or without portal venous obstruction and no extrahepatic extension than sorafenib which is now the standard treatment of advanced HCC.
- Detailed Description
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), presence or absence of macroscopic vascular invasion (obstruction of portal vein or any branch vs none) and previous chemoembolisation failure . 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 496
- 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 OR patients in whom chemoembolisation has failed after two courses (patients who have received only one course of chemoembolisation are eligible if the failure of the first round shows that a second round will have no more impact; patients who have received more than two courses of chemoembolisation are still eligible if the arterial network is perfectly normal on a CT scan in the arterial phase). Failure is defined as the absence of an objective response after two courses of treatment in the treated nodule (objective response according to modified RECIST criteria and/or EASL criteria).
- 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 150渭mol/L
- Bilirubin under or equals 50 碌mol/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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description radioembolization group SIR-Sphere The first step will check patient eligibility and prepare conditioning by performing selective mesenteric and hepatic angiography (to document the arterial tumor supply and to occlude extrahepatic vessels) and 99mTc-macroaggregated albumin scintigraphy. The second step is RADIOEMBOLIZATION therapy. One to two weeks after patient eligibility and conditioning, treatment is performed with SIR-Sphere (SIRTEX Medical Ltd.,Lane Cove,Australia). sorafenib group sorafenib Patients will receive continuous oral treatment with 800 mg of sorafenib daily (Nexavar, Bayer HealthCare Pharmaceuticals-Onyx Pharmaceuticals). Treatment interruptions and dose reductions (to 400 mg once daily) will be permitted for drug-related adverse effects. At the discretion of the investigator, the dose may be re-escalated to after the resolution of the adverse event.
- Primary Outcome Measures
Name Time Method Median overall survival time 36 months Median overall survival time since randomisation
- Secondary Outcome Measures
Name Time Method Common Terminology Criteria for Adverse Events 36 months Adverse events reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0
Progression-free survival month 6 Progression-free survival at 6 months
Health care costs 36 months Health care costs which comprise 2 parts: 1) the microcosting of Y90 radioembolization from the viewpoint of the hospital and 2) the full cost of each strategy
Response rate 36 months Response rate (complete response, partial response, stable disease)
General and hepatic specific quality of life scores 36 months General and hepatic specific quality of life scores
Trial Locations
- Locations (26)
CHU Dijon H么pital Bocage #22
馃嚝馃嚪Dijon, France
H么pital Edouard Herriot #6
馃嚝馃嚪Lyon, France
H么pital Saint Eloi #8
馃嚝馃嚪Montpellier, France
Institut Paoli Calmettes #7
馃嚝馃嚪Marseille, France
H么pital Haut Leveque #14
馃嚝馃嚪Pessac, France
CHU Saint Etienne H么pital Nord #17
馃嚝馃嚪Saint-Priest en Jarez, France
H么pital de Hautepierre #18
馃嚝馃嚪Strasbourg, France
Institut Gustave Roussy #20
馃嚝馃嚪Villejuif, France
CHU Amiens #2
馃嚝馃嚪Amiens, France
CHU Angers #3
馃嚝馃嚪Angers, France
CHRU Besan莽on H么pital Jean Minjoz #21
馃嚝馃嚪Besan莽on, France
H么pital Jean Verdier #25
馃嚝馃嚪Bondy, France
H么pital C么te de Nacre #4
馃嚝馃嚪Caen, France
H么pital Antoine B茅cl猫re #29
馃嚝馃嚪Clamart, France
Hopital beaujon #1
馃嚝馃嚪Clichy, France
Henri Mondor #24
馃嚝馃嚪Cr茅teil, France
CHU Grenoble #5
馃嚝馃嚪Grenoble, France
CHU Marseille H么pital La Timone #23
馃嚝馃嚪Marseille, France
Lyon La croix Rousse #27
馃嚝馃嚪Lyon, France
H么pital de Brabois #9
馃嚝馃嚪Nancy, France
Hotel Dieu #10
馃嚝馃嚪Nantes, France
H么pital de L'Archet #11
馃嚝馃嚪Nice, France
CHU Poitiers La Mil茅trie
馃嚝馃嚪Poitiers, France
CHU Robert Debr茅 #28
馃嚝馃嚪Reims, France
Paul Brousse #19
馃嚝馃嚪Villejuif, France
H么pital Europ茅en Georges Pompidou #13
馃嚝馃嚪Paris, France