ARQ 197-215: A randomized, placebo-controlled phase II clinical trial evaluating the c-Met inhibitor, ARQ 197, in patients (pts) with hepatocellular carcinoma (HCC).
2010; Lippincott Williams & Wilkins; Volume: 28; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2010.28.15_suppl.tps215
ISSN1527-7755
AutoresIvan Borbath, Armando Santoro, Jean‐Luc Van Laethem, Bruno Daniele, Luca Cicalese, Stefan Zeuzem, P. Buggish, Luigi Bolondi, Jonathan Strosberg, Giovanni Abbadessa,
Tópico(s)Cancer Mechanisms and Therapy
ResumoTPS215 Background: ARQ 197 is a selective, non-ATP competitive inhibitor of c-Met, the exclusive tyrosine kinase receptor for hepatocyte growth factor (HGF) implicated in tumor cell migration, invasion, proliferation, and angiogenesis. Overexpression of c-Met and HGF is associated with poor prognosis in patients with HCC. A previously reported phase I study (ASCO 2009 abstract 3523) demonstrated the safety, MTD, and PK of ARQ 197 monotherapy and this drug has now been evaluated as both monotherapy and in combination with other anti-cancer agents in over 300 cancer pts. A phase 1b study evaluating use of ARQ 197 in pts with HCC and cirrhosis revealed no worsening of liver function and preliminary evidence of both safety and efficacy. Methods: Pts are currently being enrolled into this global, randomized, double blind, placebo-controlled phase II clinical trial. Eligible pts must present with ECOG performance score <2, and have progressed to or not tolerated one prior line of systemic chemotherapy. Pts cannot present with Child-Pugh B-C cirrhotic status. Pts are being randomized in a 2:1 fashion to receive either 360 mg. oral ARQ 197 twice daily (bid) (A) or placebo (P) and are evaluated by CT or MRI scan at regular six-week intervals. Pts randomized to P are eligible for crossover to open label A following radiographic progression of disease (PD). The primary endpoint is time-to-tumor progression (TTP). Secondary objectives (or endpoints) include comparisons of the study arms for median progression-free survival (PFS), overall survival (OS), biomarker analyses, pharmacokinetics, and safety. Treatment continues until confirmed PD or unacceptable toxicity. As of 31 December 2009, 8 out of 99 required pts were enrolled and treated. Participating centers are located in Italy (8), Germany (5), Spain (5), Belgium (3), Canada (2) and the United States (2). This trial is expected to complete enrollment by the fall of 2010. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ArQule
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