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Clinical Trial
. 2015 May;17(5):708-17.
doi: 10.1093/neuonc/nou356. Epub 2015 Mar 11.

Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study

L Burt Nabors  1 , Karen L Fink  1 , Tom Mikkelsen  1 , Danica Grujicic  1 , Rafal Tarnawski  1 , Do Hyun Nam  1 , Maria Mazurkiewicz  1 , Michael Salacz  1 , Lynn Ashby  1 , Vittorina Zagonel  1 , Roberta Depenni  1 , James R Perry  1 , Christine Hicking  1 , Martin Picard  1 , Monika E Hegi  1 , Benoit Lhermitte  1 , David A Reardon  1
Affiliations
Clinical Trial

Two cilengitide regimens in combination with standard treatment for patients with newly diagnosed glioblastoma and unmethylated MGMT gene promoter: results of the open-label, controlled, randomized phase II CORE study

L Burt Nabors et al. Neuro Oncol. 2015 May.

Abstract

Background: Survival outcomes for patients with glioblastoma remain poor, particularly for patients with unmethylated O(6)-methylguanine-DNA methyltransferase (MGMT) gene promoter. This phase II, randomized, open-label, multicenter trial investigated the efficacy and safety of 2 dose regimens of the selective integrin inhibitor cilengitide combined with standard chemoradiotherapy in patients with newly diagnosed glioblastoma and an unmethylated MGMT promoter.

Methods: Overall, 265 patients were randomized (1:1:1) to standard cilengitide (2000 mg 2×/wk; n = 88), intensive cilengitide (2000 mg 5×/wk during wk 1-6, thereafter 2×/wk; n = 88), or a control arm (chemoradiotherapy alone; n = 89). Cilengitide was administered intravenously in combination with daily temozolomide (TMZ) and concomitant radiotherapy (RT; wk 1-6), followed by TMZ maintenance therapy (TMZ/RT→TMZ). The primary endpoint was overall survival; secondary endpoints included progression-free survival, pharmacokinetics, and safety and tolerability.

Results: Median overall survival was 16.3 months in the standard cilengitide arm (hazard ratio [HR], 0.686; 95% CI: 0.484, 0.972; P = .032) and 14.5 months in the intensive cilengitide arm (HR, 0.858; 95% CI: 0.612, 1.204; P = .3771) versus 13.4 months in the control arm. Median progression-free survival assessed per independent review committee was 5.6 months (HR, 0.822; 95% CI: 0.595, 1.134) and 5.9 months (HR, 0.794; 95% CI: 0.575, 1.096) in the standard and intensive cilengitide arms, respectively, versus 4.1 months in the control arm. Cilengitide was well tolerated.

Conclusions: Standard and intensive cilengitide dose regimens were well tolerated in combination with TMZ/RT→TMZ. Inconsistent overall survival and progression-free survival outcomes and a limited sample size did not allow firm conclusions regarding clinical efficacy in this exploratory phase II study.

Keywords: cilengitide; newly diagnosed glioblastoma; randomized phase II study; unmethylated MGMT promoter.

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Figures

Fig. 1.
Fig. 1.
CONSORT diagram. aIncludes 3 patients who were randomized to cilengitide intensive (CIL int) treatment but actually received cilengitide standard treatment.
Fig. 2.
Fig. 2.
Kaplan–Meier estimate for OS in the 3 treatment arms of the CORE phase II study. CIL, cilengitide; int, intensive.
Fig. 3.
Fig. 3.
Kaplan–Meier estimate for PFS assessed (A) by IRC and (B) by investigators. CIL, cilengitide; int, intensive.
See this image and copyright information in PMC

Comment in

References

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