Phase II randomized, double-blind, placebo-controlled study of tivantinib in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)

Paul Monk, Glenn Liu, Walter M. Stadler, Susan Geyer, Ying Huang, John Wright, Miguel Villalona-Calero, James Wade, Russell Szmulewitz, Shilpa Gupta, Amir Mortazavi, Robert Dreicer, Roberto Pili, Nancy Dawson, Saby George, Jorge A. Garcia

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background Tivantinib is a non-ATP competitive inhibitor of c-MET receptor tyrosine kinase that may have additional cytotoxic mechanisms including tubulin inhibition. Prostate cancer demonstrates higher c-MET expression as the disease progresses to more advanced stages and to a castration resistant state. Methods 80 patients (pts) with asymptomatic or minimally symptomatic mCRPC were assigned (2:1) to either tivantinib 360 mg PO BID or placebo (P). The primary endpoint was progression free survival (PFS). Results Of the 80 pts. enrolled, 78 (52 tivantinib, 26 P) received treatment and were evaluable. Median follow up is 8.9 months (range: 2.3 to 19.6 months). Patients treated with tivantinib had significantly better PFS vs. those treated with placebo (medians: 5.5 mo vs 3.7 mo, respectively; HR = 0.55, 95% CI: 0.33 to 0.90; p = 0.02). Grade 3 febrile neutropenia was seen in 1 patient on tivantinib while grade 3 and 4 neutropenia was recorded in 1 patient each on tivantinib and placebo. Grade 3 sinus bradycardia was recorded in two men on the tivantinib arm. Conclusions Tivantinib has mild toxicity and improved PFS in men with asymptomatic or minimally symptomatic mCRPC.

Original languageEnglish (US)
Pages (from-to)919-926
Number of pages8
JournalInvestigational New Drugs
Volume36
Issue number5
DOIs
StatePublished - Oct 1 2018

Keywords

  • Cancer
  • Castration resistant
  • Prostate
  • Tivantinib

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

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