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ASCO 2013:二线治疗之Tivantinib的3期临床试验

2013/6/6 作者:ASCO   来源:dxy 我要评论0
Tags: ASCO  Tivantinib  HGF  MET  抑制剂  

Tivantinib是HGF的受体MET的抑制剂。这是一个3期临床试验,目标患者是在前期的全身治疗(包括索拉非尼)过程中进展或无法耐受的者,且肿瘤组织免疫组化染色证实MET高表达者。计划募集303名患者,按照2:1的比例随机接受tivantinib或安慰剂治疗。预期2015年中期可以完成研究。

Metiv-HCC: A phase III clinical trial evaluating tivantinib (ARQ 197), a MET inhibitor, versus placebo as second-line in patients (pts) with MET-high inoperable hepatocellular carcinoma (HCC).
Abstract:
Background: Tivantinibis a selective, non-ATP competitive, oral inhibitor of MET,the tyrosine kinase receptor for hepatocyte growth factor (HGF). METover-expression is associated with poor prognosis in HCC patients. Aphase Ib study (Santoro et al, Br J Cancer, 2013) with tivantinib 360mgBID revealed no worsening of liver function in cirrhotic HCC pts. Arandomized, placebo-controlled phase 2 study identified HCC patientswith high tumor MET expression at immunohistochemistry (IHC) as thetarget population for tivantinib in second line (overall survival: 7.2months on tivantinib, 3.8 months on placebo, HR: 0.38, p=0.01), andselected 240mg BID as the appropriate dose for HCC patients (Santoro etal, Lancet Oncol, 2013).
Methods: Enrollment forthis phase III clinical trial (ARQ 197-A-U303, NCT01755767) has begun.Eligible pts must present with Child Pugh A; ECOG performance score <1; inoperable RECIST 1.1 measurable disease; adequate bone marrow, liver and kidney functions; no prior liver transplant. Pts must have progressed after or not tolerated one prior line of systemic therapy including sorafenib and their tumor samples must be deemed MET-High by IHC at a central laboratory to be eligible. Approximately 303 pts are randomized 2:1 to receive tivantinib 240mg PO twice daily or placebo. Pts are stratified by vascular invasion, metastases, and alphafetoprotein level, and they are evaluated by CT or MRI scan at 8-week intervals. The primary endpoint is overall survival (OS). Secondary endpoints include progression-free survival and safety. Treatment continues until confirmed disease progression or unacceptable toxicity. Pts discontinued from study treatment will be followed for survival. Participating centers are located in Europe, Australia, New Zealand, and the Americas. This trial is expected to complete enrollment by mid-2015, and an interim analysis is planned when approximately 60% of OS events are reached.
Clinical trial information: NCT01755767.



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