SorAfenib Versus RADIOEMBOLIZATION in Advanced Hepatocellular Carcinoma (SARAH)

This study is currently recruiting participants.
Verified June 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01482442
First received: November 28, 2011
Last updated: June 5, 2013
Last verified: June 2013
  Purpose

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.


Condition Intervention Phase
Liver Carcinoma
Drug: sorafenib
Drug: SIR-Sphere
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Randomized Open-labeled Trial Comparing RADIOEMBOLIZATION With Yttrium 90 Microspheres and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Median overall survival time [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Median overall survival time since randomisation


Secondary Outcome Measures:
  • Common Terminology Criteria for Adverse Events [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
    Adverse events reported according to the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0

  • Progression-free survival [ Time Frame: month 6 ] [ Designated as safety issue: No ]
    Progression-free survival at 6 months

  • Response rate [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    Response rate (complete response, partial response, stable disease)

  • General and hepatic specific quality of life scores [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    General and hepatic specific quality of life scores

  • Health care costs [ Time Frame: 36 months ] [ Designated as safety issue: No ]
    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


Estimated Enrollment: 400
Study Start Date: December 2011
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: sorafenib group
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.
Drug: 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.
Other Name: sorafenib
Active Comparator: radioembolization group
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).
Drug: 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).
Other Name: SIR-Sphere

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), 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01482442

Contacts
Contact: valerie vilgrain, PD, PhD 00 33 (0)1 40 87 53 58 valerie.vilgrain@bjn.aphp.fr

Locations
France
CHU Amiens #2 Not yet recruiting
Amiens, France, 80054
Contact: Eric NGUYEN-KHAC, PD, PhD       nguyen-khac.eric@chu-amiens.fr   
CHU Angers #3 Recruiting
Angers, France, 49933
Contact: Frederic OBERTI       froberti@chu-angers.fr   
Contact: Christophe AUBE       chaube@chu-angers.fr   
CHRU Besançon Hôpital Jean Minjoz #21 Not yet recruiting
Besançon, France, 25030
Contact: Vincent DI MARTINO       vdimartino@chu-besancon.fr   
Hôpital Jean Verdier #25 Recruiting
Bondy, France, 93140
Contact: Jean Claude TRINCHET       jean-claude.trinchet@jvr.aphp.fr   
Hôpital Côte de Nacre #4 Recruiting
Caen, France, 14033
Contact: Thông DAO       dao-t@chu-caen.fr   
Hôpital Antoine Béclère #29 Not yet recruiting
Clamart, France, 92140
Contact: Lysiane MARTHEY       lysiane.m@voila.fr   
Hopital beaujon #1 Recruiting
Clichy, France, 92110
Contact: Valerie VILGRAIN, PD, PhD    00 33 (0)1 40 87 53 58    valerie.vilgrain@bjn.aphp.fr   
Contact: Laurent CASTERA       laurent.castera@bjn.aphp.fr   
Henri Mondor #24 Not yet recruiting
Créteil, France, 94000
Contact: Charlotte COSTENTIN       charlotte.costentin@hmn.aphp.fr   
CHU Dijon Hôpital Bocage #22 Recruiting
Dijon, France, 21000
Contact: Patrick Hillon       patrick.hillon@chu-dijon.fr   
CHU Grenoble #5 Recruiting
Grenoble, France, 38043
Contact: Vincent LEROY       vleroy@chu-grenoble.fr   
Hôpital Edouard Herriot #6 Not yet recruiting
Lyon, France, 69003
Contact: Jérôme DUMORTIER       jerome.dumortier@chu-lyon.fr   
Lyon La croix Rousse #27 Not yet recruiting
Lyon, France, 69004
Contact: Philippe MERLE       philippe.merle@chu-lyon.fr   
Institut Paoli Calmettes #7 Recruiting
Marseille, France, 13009
Contact: Jean-luc RAOUL       raouljl@ipc.unicancer.fr   
CHU Marseille Hôpital La Timone #23 Recruiting
Marseille, France, 13385
Contact: René GEROLAMI       rene.gerolami@ap-hm.fr   
Contact: Jean-Francois SEITZ       Jean-francois.SEITZ@ap-hm.fr   
Hôpital Saint Eloi #8 Recruiting
Montpellier, France, 34295
Contact: Eric ASSENAT       e.assenat@gmail.com   
Contact: Georges-Philippe PAGEAUX       gp-pageaux@chu-montpellier.fr   
Hôpital de Brabois #9 Recruiting
Nancy, France, 54511
Contact: Hélène BARRAUD       h.barraud@chu-nancy.fr   
Hotel Dieu #10 Recruiting
Nantes, France, 44093
Contact: Isabelle ARCHAMBEAUD       Isabelle.ARCHAMBEAUD@chu-nantes.fr   
Hôpital de L'Archet #11 Recruiting
Nice, France, 06002
Contact: Abakar MAHAMAT       mahamat.a@chu-nice.fr   
Hôpital Européen Georges Pompidou #13 Recruiting
Paris, France, 75908
Hôpital Haut Leveque #14 Recruiting
Pessac, France, 33604
Contact: Julien VERGNIOL       julien.vergniol@chu-bordeaux.fr   
CHU Poitiers La Milétrie Recruiting
Poitiers, France, 86021
Contact: Christine SILVAIN       c.silvain@chu-poitiers.fr   
CHU Robert Debré #28 Not yet recruiting
Reims, France, 51100
Contact: Alexandra HEURGUE-BERLOT       aheurgue@chu-reims.fr   
Contact: Daniele SOMMACALE       dsommacale@chu-reims.fr   
CHU Saint Etienne Hôpital Nord #17 Recruiting
Saint-Priest en Jarez, France, 42270
Contact: Audrey PASQUION       audrey.pasquion@chu-st-etienne.fr   
Contact: Gabriele BARABINO       gabriele.barabino@chu-st-etienne.fr   
Hôpital de Hautepierre #18 Recruiting
Strasbourg, France, 67098
Contact: Bernard DUCLOS       bernard.duclos@chru-strasbourg.fr   
Contact: Philippe BACHELLIER       philippe.bachellier@chru-strasbourg.fr   
Paul Brousse #19 Recruiting
Villejuif, France, 94275
Contact: René ADAM       rene.adam@pbr.aphp.fr   
Contact: Didier SAMUEL       didier.samuel@pbr.aphp.fr   
Institut Gustave Roussy #20 Not yet recruiting
Villejuif, France, 94805
Contact: Jean LUMBROSO       jean.lumbroso@igr.fr   
Contact: Michel DUCREUX       ducreux@igr.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Ministry of Health, France
Investigators
Principal Investigator: Valerie Vilgrain, PD, PhD Department of radiology
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01482442     History of Changes
Other Study ID Numbers: P101103
Study First Received: November 28, 2011
Last Updated: June 5, 2013
Health Authority: France: Committee for the Protection of Personnes

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Liver, HCC
Liver, interventional procedures
Liver, randomized studies
Liver, targeted therapy
Liver, RADIOEMBOLIZATION

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Hepatocellular
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Sorafenib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014