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

• Published in: BMC cancer Vol. 16; no. 1; p. 856
• Main Authors: Gandhi, Mihir, Choo, Su Pin, Thng, Choon Hua, Tan, Say Beng, Low, Albert Su Chong, Cheow, Peng Chung, Goh, Anthony Soon Whatt, Tay, Kiang Hiong, Lo, Richard Hoau Gong, Goh, Brian Kim Poh, Wong, Jen San, Ng, David Chee Eng, Soo, Khee Chee, Liew, Wei Ming, Chow, Pierce K H
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 07-11-2016; BioMed Central
• Subjects: Ablation; Analysis; Antineoplastic Agents - therapeutic use; Birth control; Brachytherapy - methods; Cancer therapies; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - therapy; Clinical Protocols; Combined Modality Therapy; Female; Hepatoma; Humans; Informed consent; Liver; Liver cancer; Liver Neoplasms - pathology; Liver Neoplasms - therapy; Magnetic resonance imaging; Medical prognosis; Metastasis; Neoplasm Staging; Niacinamide - analogs & derivatives; Niacinamide - therapeutic use; Patients; Phenylurea Compounds - therapeutic use; Prognosis; Protein Kinase Inhibitors - therapeutic use; Public health; Radiation therapy; Research Design; Study Protocol; Thrombosis; Transplantation; Veins & arteries; Asia-Pacific region; Asia-Pacific; Systemic therapy; Liver cancer; Phase III; SIR-Spheres; Selective internal radiation therapy; Sorafenib; Advanced hepatocellular carcinoma; Radioembolisation; Randomized controlled trial
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-016-2868-y

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.