NCT01482442

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
496

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Dec 2011

Typical duration for phase_3

Geographic Reach
1 country

26 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

November 28, 2011

Completed
2 days until next milestone

First Posted

Study publicly available on registry

November 30, 2011

Completed
1 day until next milestone

Study Start

First participant enrolled

December 1, 2011

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2016

Completed
Last Updated

January 16, 2017

Status Verified

January 1, 2017

Enrollment Period

4.3 years

First QC Date

November 28, 2011

Last Update Submit

January 13, 2017

Conditions

Liver Carcinoma

Keywords

Liver, HCCLiver, interventional proceduresLiver, randomized studiesLiver, targeted therapyLiver, RADIOEMBOLIZATION

Outcome Measures

Primary Outcomes (1)

  • Median overall survival time

    Median overall survival time since randomisation

    36 months

Secondary Outcomes (5)

  • Common Terminology Criteria for Adverse Events

    36 months

  • Progression-free survival

    month 6

  • Response rate

    36 months

  • General and hepatic specific quality of life scores

    36 months

  • Health care costs

    36 months

Study Arms (2)

sorafenib group

ACTIVE COMPARATOR

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

radioembolization group

ACTIVE COMPARATOR

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

Interventions

sorafenibDRUG

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.

sorafenib group
SIR-SphereDRUG

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).

radioembolization group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (26)

CHU Amiens #2

Amiens, Amiens, 80054, France

Location

CHU Angers #3

Angers, Angers, 49933, France

Location

CHRU Besançon Hôpital Jean Minjoz #21

Besançon, Besançon, 25030, France

Location

Hôpital Jean Verdier #25

Bondy, Bondy, 93140, France

Location

Hôpital Côte de Nacre #4

Caen, Caen, 14033, France

Location

Hôpital Antoine Béclère #29

Clamart, Clamart, 92140, France

Location

Hopital beaujon #1

Clichy, Clichy, 92110, France

Location

Henri Mondor #24

Créteil, Créteil, 94000, France

Location

CHU Dijon Hôpital Bocage #22

Dijon, Dijon, 21000, France

Location

CHU Grenoble #5

Grenoble, Grenoble, 38043, France

Location

Hôpital Edouard Herriot #6

Lyon, Lyon, 69003, France

Location

Lyon La croix Rousse #27

Lyon, Lyon, 69004, France

Location

Institut Paoli Calmettes #7

Marseille, Marseille, 13009, France

Location

CHU Marseille Hôpital La Timone #23

Marseille, Marseille, 13385, France

Location

Hôpital Saint Eloi #8

Montpellier, Montpellier, 34295, France

Location

Hôpital de Brabois #9

Nancy, Nancy, 54511, France

Location

Hotel Dieu #10

Nantes, Nantes, 44093, France

Location

Hôpital de L'Archet #11

Nice, Nice, 06002, France

Location

Hôpital Européen Georges Pompidou #13

Paris, Paris, 75908, France

Location

Hôpital Haut Leveque #14

Pessac, Pessac, 33604, France

Location

CHU Poitiers La Milétrie

Poitiers, Poitiers, 86021, France

Location

CHU Robert Debré #28

Reims, Reims, 51100, France

Location

CHU Saint Etienne Hôpital Nord #17

Saint-Priest-en-Jarez, Saint-Priest En Jarez, 42270, France

Location

Hôpital de Hautepierre #18

Strasbourg, Strasbourg, 67098, France

Location

Paul Brousse #19

Villejuif, Villejuif, 94275, France

Location

Institut Gustave Roussy #20

Villejuif, Villejuif, 94805, France

Location

Related Publications (4)

  • Zarca K, Mimouni M, Pereira H, Chatellier G, Vilgrain V, Durand-Zaleski I; SARAH Trial Group. Cost-Utility Analysis of Transarterial Radioembolization With Yttrium-90 Resin Microspheres Compared With Sorafenib in Locally Advanced and Inoperable Hepatocellular Carcinoma. Clin Ther. 2021 Jul;43(7):1201-1212. doi: 10.1016/j.clinthera.2021.04.018. Epub 2021 May 28.

    PMID: 34059326DERIVED

  • Hermann AL, Dieudonne A, Ronot M, Sanchez M, Pereira H, Chatellier G, Garin E, Castera L, Lebtahi R, Vilgrain V; SARAH Trial Group. Relationship of Tumor Radiation-absorbed Dose to Survival and Response in Hepatocellular Carcinoma Treated with Transarterial Radioembolization with 90Y in the SARAH Study. Radiology. 2020 Sep;296(3):673-684. doi: 10.1148/radiol.2020191606. Epub 2020 Jun 30.

    PMID: 32602828DERIVED

  • Vilgrain V, Pereira H, Assenat E, Guiu B, Ilonca AD, Pageaux GP, Sibert A, Bouattour M, Lebtahi R, Allaham W, Barraud H, Laurent V, Mathias E, Bronowicki JP, Tasu JP, Perdrisot R, Silvain C, Gerolami R, Mundler O, Seitz JF, Vidal V, Aube C, Oberti F, Couturier O, Brenot-Rossi I, Raoul JL, Sarran A, Costentin C, Itti E, Luciani A, Adam R, Lewin M, Samuel D, Ronot M, Dinut A, Castera L, Chatellier G; SARAH Trial Group. Efficacy and safety of selective internal radiotherapy with yttrium-90 resin microspheres compared with sorafenib in locally advanced and inoperable hepatocellular carcinoma (SARAH): an open-label randomised controlled phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1624-1636. doi: 10.1016/S1470-2045(17)30683-6. Epub 2017 Oct 26.

    PMID: 29107679DERIVED

  • Vilgrain V, Abdel-Rehim M, Sibert A, Ronot M, Lebtahi R, Castera L, Chatellier G; SARAH Trial Group. Radioembolisation with yttrium-90 microspheres versus sorafenib for treatment of advanced hepatocellular carcinoma (SARAH): study protocol for a randomised controlled trial. Trials. 2014 Dec 3;15:474. doi: 10.1186/1745-6215-15-474.

    PMID: 25472660DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

AdenocarcinomaCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplasmsLiver NeoplasmsDigestive System NeoplasmsNeoplasms by SiteDigestive System DiseasesLiver Diseases

Intervention Hierarchy (Ancestors)

Phenylurea CompoundsUreaAmidesOrganic ChemicalsBenzene DerivativesHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsNiacinamideNicotinic AcidsAcids, HeterocyclicHeterocyclic CompoundsPyridinesHeterocyclic Compounds, 1-Ring

Study Officials

  • Valerie Vilgrain, PD, PhD

    Department of radiology

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

November 28, 2011

First Posted

November 30, 2011

Study Start

December 1, 2011

Primary Completion

April 1, 2016

Study Completion

April 1, 2016

Last Updated

January 16, 2017

Record last verified: 2017-01

Locations

FR(26)