A Phase-1b study of tivantinib (ARQ 197) in adult patients with hepatocellular carcinoma and cirrhosis - PubMed (original) (raw)

Clinical Trial

. 2013 Jan 15;108(1):21-4.

doi: 10.1038/bjc.2012.556. Epub 2013 Jan 3.

M Simonelli, C Rodriguez-Lope, P Zucali, L H Camacho, A Granito, N Senzer, L Rimassa, G Abbadessa, B Schwartz, M Lamar, R E Savage, J Bruix

Affiliations

Clinical Trial

A Phase-1b study of tivantinib (ARQ 197) in adult patients with hepatocellular carcinoma and cirrhosis

A Santoro et al. Br J Cancer. 2013.

Abstract

Background: The mesenchymal-epithelial transition factor (MET) receptor is dysregulated in hepatocellular carcinoma (HCC), and tivantinib (ARQ 197) is an oral, selective, MET inhibitor.

Methods: This Phase-1b study assessed tivantinib safety as primary objective in patients with previously treated HCC and Child-Pugh A or B liver cirrhosis. Patients received oral tivantinib 360 mg twice daily until disease progression or unacceptable toxicity.

Results: Among 21 HCC patients, common drug-related adverse events (AEs) were neutropaenia, anaemia, asthenia, leucopaenia, anorexia, diarrhoea, and fatigue. No drug-related worsening of liver function or performance status occurred, but one Child-Pugh B patient experienced drug-related bilirubin increase. Four patients had drug-related serious AEs, including one neutropaenia-related death. Haematologic toxicities were more frequent than in previous tivantinib studies but were manageable with prompt therapy. Best response was stable disease (median, 5.3 months) in 9 of 16 evaluable patients (56%). Median time to progression was 3.3 months.

Conclusion: Tivantinib demonstrated a manageable safety profile and preliminary antitumour activity in patients with HCC and Child-Pugh A or B cirrhosis.

PubMed Disclaimer

Conflict of interest statement

JB is a consultant for Abbott, AngioDynamics, ArQule, Bayer, BioAlliance, Biocompatibles, BMS, Eisai, GlaxoSmithKline, ImClone, Jennerex, Kowa, Lilly, MedImmune, Novartis, OSI, Pharmexa, Roche, Sanofi, Schering-Plough, and Sumitomo. AS is a consultant for ArQule and Bayer. GA, ML, BS, and RS are employees of ArQule. LR received travel grants from ArQule. The remaining authors declare no conflict of interest.

Figures

Figure 1

Figure 1

Maximum change from baseline in tumour burden in the evaluable efficacy population (_n_=16).

Similar articles

Cited by

References

    1. Bagai R, Fan W, Ma PC (2010) ARQ-197, an oral small molecule inhibitor of c-Met for the treatment of solid tumors. IDrugs 13(6): 404–414 - PubMed
    1. Bathala MS, Nakai D, Murai T, Pickersgill F, Zahir H, Tokui T (2012) Absorption, distribution, metabolism, and excretion of 14C-labeled tivantinib (ARQ 197) in healthy male subjects. 103rd Annual Meeting of the American Association for Cancer Research 31 Mar–4 Apr 2012; Chicago, IL. Abstract 747
    1. Boix L, Rosa JL, Ventura F, Castells A, Bruix J, Rodes J, Bartrons R (1994) c-met mRNA overexpression in human hepatocellular carcinoma. Hepatology 19(1): 88–91 - PubMed
    1. Bruix J, Sherman M (2005) Management of hepatocellular carcinoma. Hepatology 42(5): 1208–1236 - PubMed
    1. Bruix J, Sherman M (2011) Management of hepatocellular carcinoma: an update. Hepatology 53(3): 1020–1022 - PMC - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources