Phase 3 - XL184 in Combination with Atezolizumab vs Sorafenib in HCC
Research type
Research Study
Full title
A Randomized, Controlled Phase 3 Study of Cabozantinib (XL184) in Combination with Atezolizumab versus Sorafenib in Subjects with Advanced Hepatocellular Carcinoma Who Have Not Received Previous Systemic Anticancer Therapy
IRAS ID
255993
Contact name
Tim Meyer
Contact email
Sponsor organisation
Exelixis, Inc.
Eudract number
2018-003354-24
Clinicaltrials.gov Identifier
Duration of Study in the UK
3 years, 11 months, 0 days
Research summary
Liver cancer is the second most frequent cause of cancer deaths worldwide. Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, accounting for approximately 90% of cases. In 2015, 854,000 new liver cancer cases were reported worldwide and 810,000 deaths occurred (Global Burden of Disease Liver Cancer 2017; EASL 2018). The estimated incidence and mortality rates of liver cancer in the USA in 2016 were approximately 42,000 and 30,000 cases, respectively (American Cancer Society 2018); incidence and mortality in the EU in 2012 were 52,000 and 48,000 cases, respectively (Ferlay et al 2013).
The purpose of this study is to find out if cabozantinib in combination with atezolizumab is effective in treating liver cancer compared to sorafenib alone in people who have not received prior treatment. This study will also examine how well people with liver cancer, who have not received prior treatment, tolerate cabozantinib alone, and how well it works in treating their cancer. Additionally there will be an exploratory arm to evaluate the single-agent safety and activity of cabozantinib. Approximately 640 eligible participants with advanced or metastatic HCC will be randomized in a 6:3:1 ratio at approximately 200 sites in this study. It is estimated that participants will receive study treatment for an average of approximately 6 months. Participants will be followed until death, withdrawal of consent, or Sponsor decision to no longer collect survival data.
The current standard of care for the systemic treatment of advanced unresectable HCC is sorafenib, which is a small-molecule inhibitor of vascular endothelial growth factor receptor (VEGFR) and other protein kinases.
Based on all available data, further evaluation of cabozantinib in combination atezolizumab is warranted and has the potential to improve the clinical outcome of participants with advanced HCC due to synergistic activities of the two agents.REC name
Yorkshire & The Humber - Sheffield Research Ethics Committee
REC reference
19/YH/0013
Date of REC Opinion
14 Feb 2019
REC opinion
Further Information Favourable Opinion