A randomized phase I/II study of ABT-888 in combination with temozolomide in recurrent temozolomide resistant glioblastoma: An NRG oncology RTOG group study

H. Ian Robins, Peixin Zhang, Mark R. Gilbert, Arnab Chakravarti, John F. de Groot, Sean A. Grimm, Fen Wang, Frank S. Lieberman, Andra Krauze, Andy M. Trotti, Nimish Mohile, Andrew Y.J. Kee, Howard Colman, Robert Cavaliere, Santosh Kesari, Steven J. Chmura, Minesh Mehta

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

This study tested the hypothesis that ABT-888 (velparib), a poly (ADP-ribose) polymerase (PARP) inhibitor, can modulate temozolomide (TMZ) resistance in recurrent TMZ refractory glioblastoma patients. The combination regimen (TMZ/ABT-888) was tested using two randomized schedules (5 vs. 21 days), with 6-month progression free survival (PFS6) as the primary endpoint. The maximum tolerated dose (MTD) for TMZ using the 21 day of 28 TMZ schedule, in concert with 40 mg BID ABT-888 was determined in a phase I portion of this study, and previously reported to be 75 mg/m2(arm1). The MTD for ABT-888 (40 mg BID) and the 5 of 28 day TMZ (150-200 mg/m2) schedule was known from prior trials (arm2). Two cohorts were studied: bevacizumab (BEV) naïve (n = 151), and BEV refractory (n = 74). Overall ten patients were ineligible. The incidence rate of grade 3/4 myelosuppression over all was 20.0%. For the BEV refractory cohort, the PFS 6 was 4.4%; for the BEV naïve cohort, PFS6 was 17%. Overall survival was similar for both arms in both the BEV naïve [median survival time (MST) 10.3 M; 95% CI 8.4-12] and BEV refractory cohort (MST 4.7 M; 95%CI 3.5-5.6). The median PFS was essentially the same for both arms and both cohorts at ~2.0 M (95% CI 1.9-2.1).

Original languageEnglish (US)
Pages (from-to)309-316
Number of pages8
JournalJournal of neuro-oncology
Volume126
Issue number2
DOIs
StatePublished - Jan 2016

Keywords

  • ABT-888
  • Glioblastoma
  • Temozolomide
  • Velparib

ASJC Scopus subject areas

  • Oncology
  • Neurology
  • Clinical Neurology
  • Cancer Research

MD Anderson CCSG core facilities

  • Clinical and Translational Research Center
  • Clinical Trials Office

Fingerprint

Dive into the research topics of 'A randomized phase I/II study of ABT-888 in combination with temozolomide in recurrent temozolomide resistant glioblastoma: An NRG oncology RTOG group study'. Together they form a unique fingerprint.

Cite this