Single administration of Selective Internal Radiation Therapy versus continuous treatment with sorafeNIB in locally advanced hepatocellular carcinoma (SIRveNIB): study protocol for a phase iii randomized controlled trial.
Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients.



This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy.



Definitive data comparing these two therapies will help to determine clinical practice in the large group of patients with locally advanced HCC and improve outcomes for such patients.



ClinicalTrials.gov identifier, NCT01135056 , first received 24, May 2010.
Biostatistics, Singapore Clinical Research Institute, #02-01, Nanos, 31 Biopolis Way, Singapore, Singapore.|Centre for Quantitative Medicine, Duke-NUS Medical School, 8 College Road, Singapore, Singapore.|Tampere Center for Child Health Research, University of Tampere and Tampere University Hospital, Tempere, Finland.
Mihir
M
Gandhi
Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore, Singapore.
Su Pin
SP
Choo
Division of Oncologic Imaging, National Cancer Centre Singapore, 11 Hospital Drive, Singapore, Singapore.
Choon Hua
CH
Thng
Office of Research, Singapore Health Services, 31 Third Hospital Avenue, #03-03 Bowyer Block C, Singapore, Singapore.|Clinical Sciences, Duke-NUS Medical School, 8 College Road, Singapore, Singapore.
Say Beng
SB
Tan
Department of Diagnostic Radiology, Singapore General Hospital, Outram Road, Singapore, Singapore.
Albert Su Chong
AS
Low
Department of Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, Singapore.
Peng Chung
PC
Cheow
Department of Nuclear Medicine and PET, Singapore General Hospital, Outram Road, Singapore, Singapore.
Anthony Soon Whatt
AS
Goh
Department of Diagnostic Radiology, Singapore General Hospital, Outram Road, Singapore, Singapore.
Kiang Hiong
KH
Tay
Department of Diagnostic Radiology, Singapore General Hospital, Outram Road, Singapore, Singapore.
Richard Hoau Gong
RH
Lo
Department of Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, Singapore.
Brian Kim Poh
BK
Goh
Department of Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, Singapore.
Jen San
JS
Wong
Department of Nuclear Medicine and PET, Singapore General Hospital, Outram Road, Singapore, Singapore.
David Chee Eng
DC
Ng
Division of Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Drive, Singapore, Singapore.
Khee Chee
KC
Soo
Project Management, Singapore Clinical Research Institute, #02-01, Nanos, 31 Biopolis Way, Singapore, Singapore.
Wei Ming
WM
Liew
Department of Hepato-pancreato-biliary and Transplant Surgery, Singapore General Hospital, Outram Road, Singapore, Singapore. pierce.chow.k.h@singhealth.com.sg.|Office of Clinical, Academic and Faculty Affairs, Duke-NUS Medical School, 8 College Road, Singapore, Singapore. pierce.chow.k.h@singhealth.com.sg.|Program in Translational and Clinical Liver Research, National Cancer Centre Singapore, Singapore, Singapore. pierce.chow.k.h@singhealth.com.sg.
Pierce K H
0000-0003-0584-2584
PK
Chow
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001918:Brachytherapy / Q000379:methods; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000628:therapy*; D002985:Clinical Protocols; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology* / Q000628:therapy*; D009367:Neoplasm Staging; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012107:Research Design; D000077157:Sorafenib
D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib
Advanced hepatocellular carcinoma; Asia-Pacific; Liver cancer; Phase III; Radioembolisation; Randomized controlled trial; SIR-Spheres; Selective internal radiation therapy; Sorafenib; Systemic therapy