Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme

David A. Reardon, Karen L. Fink, Tom Mikkelsen, Timothy F. Cloughesy, Alison O'Neill, Scott Plotkin, Michael Glantz, Paula Ravin, Jeffrey J. Raizer, Keith M. Rich, David Schiff, William R. Shapiro, Susan Burdette-Radoux, Edward Dropcho, Sabine M. Wittemer, Johannes Nippgen, Martin Picard, L. Burt Nabors

Research output: Contribution to journalArticle

347 Citations (Scopus)

Abstract

Purpose: Cilengitide, an inhibitor of αvβ3 and αvβ5 integrin receptors, demonstrated minimal toxicity and durable activity across a wide range of doses administered to adults with recurrent glioblastoma multiforme (GBM) in a prior phase I study. The current multicenter phase II study was conducted to evaluate the activity and safety of cilengitide in GBM patients at first recurrence. Patients and Methods: Eligible patients were randomly assigned to receive either 500 or 2,000 mg of cilengitide twice weekly on a continuous basis. Patients were assessed every 4 weeks. The primary end point was 6-month progression-free survival (PFS) rate. Secondary end points included PFS, overall survival (OS), and radiographic response, as well as quality-of-life and pharmacokinetic assessments. Results: Eighty-one patients were enrolled, including 41 on the 500-mg arm and 40 on the 2,000-mg arm. The safety profile of cilengitide was excellent, with no significant reproducible toxicities observed on either arm. Antitumor activity was observed in both treatment cohorts but trended more favorably among patients treated with 2,000 mg, including a 6-month PFS of 15% and a median OS of 9.9 months. Conclusion: Cilengitide monotherapy is well tolerated and exhibits modest antitumor activity among recurrent GBM patients. Additional studies integrating cilengitide into combinatorial regimens for GBM are warranted.

Original languageEnglish (US)
Pages (from-to)5610-5617
Number of pages8
JournalJournal of Clinical Oncology
Volume26
Issue number34
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

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Glioblastoma
Aspartic Acid
Integrins
Glycine
Arginine
Peptides
Disease-Free Survival
Safety
Survival
Cilengitide
Survival Rate
Pharmacokinetics
Quality of Life
Recurrence

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. / Reardon, David A.; Fink, Karen L.; Mikkelsen, Tom; Cloughesy, Timothy F.; O'Neill, Alison; Plotkin, Scott; Glantz, Michael; Ravin, Paula; Raizer, Jeffrey J.; Rich, Keith M.; Schiff, David; Shapiro, William R.; Burdette-Radoux, Susan; Dropcho, Edward; Wittemer, Sabine M.; Nippgen, Johannes; Picard, Martin; Nabors, L. Burt.

In: Journal of Clinical Oncology, Vol. 26, No. 34, 01.12.2008, p. 5610-5617.

Research output: Contribution to journalArticle

Reardon, DA, Fink, KL, Mikkelsen, T, Cloughesy, TF, O'Neill, A, Plotkin, S, Glantz, M, Ravin, P, Raizer, JJ, Rich, KM, Schiff, D, Shapiro, WR, Burdette-Radoux, S, Dropcho, E, Wittemer, SM, Nippgen, J, Picard, M & Nabors, LB 2008, 'Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme', Journal of Clinical Oncology, vol. 26, no. 34, pp. 5610-5617. https://doi.org/10.1200/JCO.2008.16.7510
Reardon, David A. ; Fink, Karen L. ; Mikkelsen, Tom ; Cloughesy, Timothy F. ; O'Neill, Alison ; Plotkin, Scott ; Glantz, Michael ; Ravin, Paula ; Raizer, Jeffrey J. ; Rich, Keith M. ; Schiff, David ; Shapiro, William R. ; Burdette-Radoux, Susan ; Dropcho, Edward ; Wittemer, Sabine M. ; Nippgen, Johannes ; Picard, Martin ; Nabors, L. Burt. / Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. In: Journal of Clinical Oncology. 2008 ; Vol. 26, No. 34. pp. 5610-5617.
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T1 - Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme

AU - Reardon, David A.

AU - Fink, Karen L.

AU - Mikkelsen, Tom

AU - Cloughesy, Timothy F.

AU - O'Neill, Alison

AU - Plotkin, Scott

AU - Glantz, Michael

AU - Ravin, Paula

AU - Raizer, Jeffrey J.

AU - Rich, Keith M.

AU - Schiff, David

AU - Shapiro, William R.

AU - Burdette-Radoux, Susan

AU - Dropcho, Edward

AU - Wittemer, Sabine M.

AU - Nippgen, Johannes

AU - Picard, Martin

AU - Nabors, L. Burt

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Y1 - 2008/12/1

N2 - Purpose: Cilengitide, an inhibitor of αvβ3 and αvβ5 integrin receptors, demonstrated minimal toxicity and durable activity across a wide range of doses administered to adults with recurrent glioblastoma multiforme (GBM) in a prior phase I study. The current multicenter phase II study was conducted to evaluate the activity and safety of cilengitide in GBM patients at first recurrence. Patients and Methods: Eligible patients were randomly assigned to receive either 500 or 2,000 mg of cilengitide twice weekly on a continuous basis. Patients were assessed every 4 weeks. The primary end point was 6-month progression-free survival (PFS) rate. Secondary end points included PFS, overall survival (OS), and radiographic response, as well as quality-of-life and pharmacokinetic assessments. Results: Eighty-one patients were enrolled, including 41 on the 500-mg arm and 40 on the 2,000-mg arm. The safety profile of cilengitide was excellent, with no significant reproducible toxicities observed on either arm. Antitumor activity was observed in both treatment cohorts but trended more favorably among patients treated with 2,000 mg, including a 6-month PFS of 15% and a median OS of 9.9 months. Conclusion: Cilengitide monotherapy is well tolerated and exhibits modest antitumor activity among recurrent GBM patients. Additional studies integrating cilengitide into combinatorial regimens for GBM are warranted.

AB - Purpose: Cilengitide, an inhibitor of αvβ3 and αvβ5 integrin receptors, demonstrated minimal toxicity and durable activity across a wide range of doses administered to adults with recurrent glioblastoma multiforme (GBM) in a prior phase I study. The current multicenter phase II study was conducted to evaluate the activity and safety of cilengitide in GBM patients at first recurrence. Patients and Methods: Eligible patients were randomly assigned to receive either 500 or 2,000 mg of cilengitide twice weekly on a continuous basis. Patients were assessed every 4 weeks. The primary end point was 6-month progression-free survival (PFS) rate. Secondary end points included PFS, overall survival (OS), and radiographic response, as well as quality-of-life and pharmacokinetic assessments. Results: Eighty-one patients were enrolled, including 41 on the 500-mg arm and 40 on the 2,000-mg arm. The safety profile of cilengitide was excellent, with no significant reproducible toxicities observed on either arm. Antitumor activity was observed in both treatment cohorts but trended more favorably among patients treated with 2,000 mg, including a 6-month PFS of 15% and a median OS of 9.9 months. Conclusion: Cilengitide monotherapy is well tolerated and exhibits modest antitumor activity among recurrent GBM patients. Additional studies integrating cilengitide into combinatorial regimens for GBM are warranted.

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