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 journalArticle

3 Citations (Scopus)

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)
JournalInvestigational New Drugs
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Castration
Prostatic Neoplasms
Placebos
Disease-Free Survival
Proto-Oncogene Proteins c-met
Febrile Neutropenia
ARQ 197
Tubulin
Bradycardia
Neutropenia

Keywords

  • Cancer
  • Castration resistant
  • Prostate
  • Tivantinib

ASJC Scopus subject areas

  • Oncology
  • Pharmacology
  • Pharmacology (medical)

Cite this

Phase II randomized, double-blind, placebo-controlled study of tivantinib in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). / Monk, Paul; Liu, Glenn; Stadler, Walter M.; Geyer, Susan; Huang, Ying; Wright, John; Villalona-Calero, Miguel; Wade, James; Szmulewitz, Russell; Gupta, Shilpa; Mortazavi, Amir; Dreicer, Robert; Pili, Roberto; Dawson, Nancy; George, Saby; Garcia, Jorge A.

In: Investigational New Drugs, 01.01.2018.

Research output: Contribution to journalArticle

Monk, P, Liu, G, Stadler, WM, Geyer, S, Huang, Y, Wright, J, Villalona-Calero, M, Wade, J, Szmulewitz, R, Gupta, S, Mortazavi, A, Dreicer, R, Pili, R, Dawson, N, George, S & Garcia, JA 2018, 'Phase II randomized, double-blind, placebo-controlled study of tivantinib in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)', Investigational New Drugs. https://doi.org/10.1007/s10637-018-0630-9
Monk, Paul ; Liu, Glenn ; Stadler, Walter M. ; Geyer, Susan ; Huang, Ying ; Wright, John ; Villalona-Calero, Miguel ; Wade, James ; Szmulewitz, Russell ; Gupta, Shilpa ; Mortazavi, Amir ; Dreicer, Robert ; Pili, Roberto ; Dawson, Nancy ; George, Saby ; Garcia, Jorge A. / Phase II randomized, double-blind, placebo-controlled study of tivantinib in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC). In: Investigational New Drugs. 2018.
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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.",
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T1 - Phase II randomized, double-blind, placebo-controlled study of tivantinib in men with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC)

AU - Monk, Paul

AU - Liu, Glenn

AU - Stadler, Walter M.

AU - Geyer, Susan

AU - Huang, Ying

AU - Wright, John

AU - Villalona-Calero, Miguel

AU - Wade, James

AU - Szmulewitz, Russell

AU - Gupta, Shilpa

AU - Mortazavi, Amir

AU - Dreicer, Robert

AU - Pili, Roberto

AU - Dawson, Nancy

AU - George, Saby

AU - Garcia, Jorge A.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

KW - Cancer

KW - Castration resistant

KW - Prostate

KW - Tivantinib

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