A safety run-in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306)

L. Burt Nabors, Thomas Mikkelsen, Monika E. Hegi, Xiaobu Ye, Tracy Batchelor, Glenn Lesser, David Peereboom, Myrna R. Rosenfeld, Jeff Olsen, Steve Brem, Joy D. Fisher, Stuart A Grossman

Research output: Contribution to journalArticle

Abstract

Background: Cilengitide is a selective integrin inhibitor that is well tolerated and has demonstrated biologic activity in patients with recurrent malignant glioma. The primary objectives of this randomized phase 2 trial were to determine the safety and efficacy of cilengitide when combined with radiation and temozolomide for patients with newly diagnosed glioblastoma multiforme and to select a dose for comparative clinical testing. Methods: In total, 112 patients were accrued. Eighteen patients received standard radiation and temozolomide with cilengitide in a safety run-in phase followed by a randomized phase 2 trial with 94 patients assigned to either a 500 mg dose group or 2000 mg dose group. The trial was designed to estimate overall survival benefit compared with a New Approaches to Brain Tumor Therapy (NABTT) Consortium internal historic control and data from the published European Organization for Research and Treatment of Cancer (EORTC) trial EORTC 26981. Results: Cilengitide at all doses studied was well tolerated with radiation and temozolomide. The median survival was 19.7 months for all patients, 17.4 months for the patients in the 500 mg dose group, 20.8 months for patients in the 2000 mg dose group, 30 months for patients who had methylated O6-methylguanine-DNA methyltransferase (MGMT) status, and 17.4 months for patients who had unmethylated MGMT status. For patients aged ≤70 years, the median survival and survival at 24 months was superior to what was observed in the EORTC trial (20.7 months vs 14.6 months and 41% vs 27%, respectively; P =.008). Conclusions: Cilengitide was well tolerated when combined with standard chemoradiation and may improve survival for patients newly diagnosed with glioblastoma multiforme regardless of MGMT methylation status. The authors concluded that, from an efficacy and safety standpoint, future trials of this agent in this population should use the 2000 mg dose.

Original languageEnglish (US)
Pages (from-to)5601-5607
Number of pages7
JournalCancer
Volume118
Issue number22
DOIs
StatePublished - Nov 15 2012

Fingerprint

Glioblastoma
Brain Neoplasms
Safety
temozolomide
Methyltransferases
Therapeutics
Survival
Radiation
Cilengitide
Research
Neoplasms
DNA
DNA Methylation
Integrins
Glioma

Keywords

  • angiogenesis
  • cilengitide
  • clinical trial
  • glioblastoma
  • integrin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A safety run-in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306). / Nabors, L. Burt; Mikkelsen, Thomas; Hegi, Monika E.; Ye, Xiaobu; Batchelor, Tracy; Lesser, Glenn; Peereboom, David; Rosenfeld, Myrna R.; Olsen, Jeff; Brem, Steve; Fisher, Joy D.; Grossman, Stuart A.

In: Cancer, Vol. 118, No. 22, 15.11.2012, p. 5601-5607.

Research output: Contribution to journalArticle

Nabors, LB, Mikkelsen, T, Hegi, ME, Ye, X, Batchelor, T, Lesser, G, Peereboom, D, Rosenfeld, MR, Olsen, J, Brem, S, Fisher, JD & Grossman, SA 2012, 'A safety run-in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306)', Cancer, vol. 118, no. 22, pp. 5601-5607. https://doi.org/10.1002/cncr.27585
Nabors, L. Burt ; Mikkelsen, Thomas ; Hegi, Monika E. ; Ye, Xiaobu ; Batchelor, Tracy ; Lesser, Glenn ; Peereboom, David ; Rosenfeld, Myrna R. ; Olsen, Jeff ; Brem, Steve ; Fisher, Joy D. ; Grossman, Stuart A. / A safety run-in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306). In: Cancer. 2012 ; Vol. 118, No. 22. pp. 5601-5607.
@article{951a4f10b32541029096be2aaa94bcea,
title = "A safety run-in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306)",
abstract = "Background: Cilengitide is a selective integrin inhibitor that is well tolerated and has demonstrated biologic activity in patients with recurrent malignant glioma. The primary objectives of this randomized phase 2 trial were to determine the safety and efficacy of cilengitide when combined with radiation and temozolomide for patients with newly diagnosed glioblastoma multiforme and to select a dose for comparative clinical testing. Methods: In total, 112 patients were accrued. Eighteen patients received standard radiation and temozolomide with cilengitide in a safety run-in phase followed by a randomized phase 2 trial with 94 patients assigned to either a 500 mg dose group or 2000 mg dose group. The trial was designed to estimate overall survival benefit compared with a New Approaches to Brain Tumor Therapy (NABTT) Consortium internal historic control and data from the published European Organization for Research and Treatment of Cancer (EORTC) trial EORTC 26981. Results: Cilengitide at all doses studied was well tolerated with radiation and temozolomide. The median survival was 19.7 months for all patients, 17.4 months for the patients in the 500 mg dose group, 20.8 months for patients in the 2000 mg dose group, 30 months for patients who had methylated O6-methylguanine-DNA methyltransferase (MGMT) status, and 17.4 months for patients who had unmethylated MGMT status. For patients aged ≤70 years, the median survival and survival at 24 months was superior to what was observed in the EORTC trial (20.7 months vs 14.6 months and 41{\%} vs 27{\%}, respectively; P =.008). Conclusions: Cilengitide was well tolerated when combined with standard chemoradiation and may improve survival for patients newly diagnosed with glioblastoma multiforme regardless of MGMT methylation status. The authors concluded that, from an efficacy and safety standpoint, future trials of this agent in this population should use the 2000 mg dose.",
keywords = "angiogenesis, cilengitide, clinical trial, glioblastoma, integrin",
author = "Nabors, {L. Burt} and Thomas Mikkelsen and Hegi, {Monika E.} and Xiaobu Ye and Tracy Batchelor and Glenn Lesser and David Peereboom and Rosenfeld, {Myrna R.} and Jeff Olsen and Steve Brem and Fisher, {Joy D.} and Grossman, {Stuart A}",
year = "2012",
month = "11",
day = "15",
doi = "10.1002/cncr.27585",
language = "English (US)",
volume = "118",
pages = "5601--5607",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "22",

}

TY - JOUR

T1 - A safety run-in and randomized phase 2 study of cilengitide combined with chemoradiation for newly diagnosed glioblastoma (NABTT 0306)

AU - Nabors, L. Burt

AU - Mikkelsen, Thomas

AU - Hegi, Monika E.

AU - Ye, Xiaobu

AU - Batchelor, Tracy

AU - Lesser, Glenn

AU - Peereboom, David

AU - Rosenfeld, Myrna R.

AU - Olsen, Jeff

AU - Brem, Steve

AU - Fisher, Joy D.

AU - Grossman, Stuart A

PY - 2012/11/15

Y1 - 2012/11/15

N2 - Background: Cilengitide is a selective integrin inhibitor that is well tolerated and has demonstrated biologic activity in patients with recurrent malignant glioma. The primary objectives of this randomized phase 2 trial were to determine the safety and efficacy of cilengitide when combined with radiation and temozolomide for patients with newly diagnosed glioblastoma multiforme and to select a dose for comparative clinical testing. Methods: In total, 112 patients were accrued. Eighteen patients received standard radiation and temozolomide with cilengitide in a safety run-in phase followed by a randomized phase 2 trial with 94 patients assigned to either a 500 mg dose group or 2000 mg dose group. The trial was designed to estimate overall survival benefit compared with a New Approaches to Brain Tumor Therapy (NABTT) Consortium internal historic control and data from the published European Organization for Research and Treatment of Cancer (EORTC) trial EORTC 26981. Results: Cilengitide at all doses studied was well tolerated with radiation and temozolomide. The median survival was 19.7 months for all patients, 17.4 months for the patients in the 500 mg dose group, 20.8 months for patients in the 2000 mg dose group, 30 months for patients who had methylated O6-methylguanine-DNA methyltransferase (MGMT) status, and 17.4 months for patients who had unmethylated MGMT status. For patients aged ≤70 years, the median survival and survival at 24 months was superior to what was observed in the EORTC trial (20.7 months vs 14.6 months and 41% vs 27%, respectively; P =.008). Conclusions: Cilengitide was well tolerated when combined with standard chemoradiation and may improve survival for patients newly diagnosed with glioblastoma multiforme regardless of MGMT methylation status. The authors concluded that, from an efficacy and safety standpoint, future trials of this agent in this population should use the 2000 mg dose.

AB - Background: Cilengitide is a selective integrin inhibitor that is well tolerated and has demonstrated biologic activity in patients with recurrent malignant glioma. The primary objectives of this randomized phase 2 trial were to determine the safety and efficacy of cilengitide when combined with radiation and temozolomide for patients with newly diagnosed glioblastoma multiforme and to select a dose for comparative clinical testing. Methods: In total, 112 patients were accrued. Eighteen patients received standard radiation and temozolomide with cilengitide in a safety run-in phase followed by a randomized phase 2 trial with 94 patients assigned to either a 500 mg dose group or 2000 mg dose group. The trial was designed to estimate overall survival benefit compared with a New Approaches to Brain Tumor Therapy (NABTT) Consortium internal historic control and data from the published European Organization for Research and Treatment of Cancer (EORTC) trial EORTC 26981. Results: Cilengitide at all doses studied was well tolerated with radiation and temozolomide. The median survival was 19.7 months for all patients, 17.4 months for the patients in the 500 mg dose group, 20.8 months for patients in the 2000 mg dose group, 30 months for patients who had methylated O6-methylguanine-DNA methyltransferase (MGMT) status, and 17.4 months for patients who had unmethylated MGMT status. For patients aged ≤70 years, the median survival and survival at 24 months was superior to what was observed in the EORTC trial (20.7 months vs 14.6 months and 41% vs 27%, respectively; P =.008). Conclusions: Cilengitide was well tolerated when combined with standard chemoradiation and may improve survival for patients newly diagnosed with glioblastoma multiforme regardless of MGMT methylation status. The authors concluded that, from an efficacy and safety standpoint, future trials of this agent in this population should use the 2000 mg dose.

KW - angiogenesis

KW - cilengitide

KW - clinical trial

KW - glioblastoma

KW - integrin

UR - http://www.scopus.com/inward/record.url?scp=84868193304&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84868193304&partnerID=8YFLogxK

U2 - 10.1002/cncr.27585

DO - 10.1002/cncr.27585

M3 - Article

VL - 118

SP - 5601

EP - 5607

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 22

ER -