An open-label, randomized phase II study comparing first-line treatment with dovitinib (TKI258) versus sorafenib in patients with advanced hepatocellular carcinoma

Autor: Eugene Tan, Cathy Reddick, Ann-Lii Cheng, Michael Shi, Yong Zhang, Yongyu Wang, Ho Yeong Lim, Ronnie T.P. Poon, Sumitra Throngprasert
Rok vydání: 2012
Předmět:
Zdroj: Journal of Clinical Oncology. 30:TPS4147-TPS4147
ISSN: 1527-7755
0732-183X
DOI: 10.1200/jco.2012.30.15_suppl.tps4147
Popis: TPS4147 Background: Hepatocellular carcinoma (HCC) is a highly vascularized tumor that may rely on tumor angiogenesis for growth, invasion, and metastasis. Inhibition of the vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor (PDGFR) pathways temporarily prevents HCC tumor progression. However, because the fibroblast growth factor receptor (FGFR) pathway can serve as an escape pathway for these tumors, simultaneous inhibition of FGFR may be required to provide a sustainable antitumor response. Dovitinib (TKI258) has been shown to be a potent oral tyrosine kinase inhibitor that inhibits multiple angiogenic factors, including FGFR, VEGFR, and PDGFR, with IC50 values of < 20 nM. Preclinical studies in HCC xenograft models have demonstrated that the antitumor effects of dovitinib are superior to those of the kinase inhibitor sorafenib, which is approved for use in advanced HCC. These data support additional testing of dovitinib in advanced HCC patients. Methods: This study (NCT01232296) is an open-label, randomized phase II trial being conducted at multiple centers in the Asia-Pacific region. Adult patients are eligible if they have advanced HCC (Barcelona Clinic Liver Cancer stage C) with Child-Pugh class A cirrhotic status. Patients must also have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and cannot be eligible for (or have had disease progression after) surgical or locoregional therapies. Patients are randomized 1:1 to receive dovitinib (500 mg/day on a 5-days-on/2-days-off dosing schedule) or sorafenib (400 mg twice daily). Patients will be treated until disease progression, unacceptable toxicity, death, or discontinuation for any other reason. No treatment crossover will be permitted. The primary end point of this trial is overall survival. Secondary end points include time to tumor progression, disease control rate, time to definitive deterioration in ECOG status, safety, and pharmacokinetics. The pharmacodynamic effects of dovitinib and sorafenib on plasma/serum biomarkers will also be explored. As of 30 January 2012, 93 of the planned 150 patients have been enrolled.
Databáze: OpenAIRE
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