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Clinical Trial
. 2007 May 1;25(13):1651-7.
doi: 10.1200/JCO.2006.06.6514.

Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma

L Burt Nabors  1 , Tom Mikkelsen, Steven S Rosenfeld, Fred Hochberg, Narasimha S Akella, Joy D Fisher, Gretchen A Cloud, Yu Zhang, Kathryn Carson, Sabine M Wittemer, A Dimitrios Colevas, Stuart A Grossman
Affiliations
Clinical Trial

Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma

L Burt Nabors et al. J Clin Oncol. .

Abstract

Purpose: This multi-institutional phase I trial was designed to determine the maximum-tolerated dose (MTD) of cilengitide (EMD 121974) and to evaluate the use of perfusion magnetic resonance imaging (MRI) in patients with recurrent malignant glioma.

Patients and methods: Patients received cilengitide twice weekly on a continuous basis. A treatment cycle was defined as 4 weeks. Treatment-related dose-limiting toxicity (DLT) was defined as any grade 3 or 4 nonhematologic toxicity or grade 4 hematologic toxicity of any duration.

Results: A total of 51 patients were enrolled in cohorts of six patients to doses of 120, 240, 360, 480, 600, 1,200, 1,800, and 2,400 mg/m2 administered as a twice weekly intravenous infusion. Three patients progressed early and were inevaluable for toxicity assessment. The DLTs observed were one thrombosis (120 mg/m2), one grade 4 joint and bone pain (480 mg/m2), one thrombocytopenia (600 mg/m2) and one anorexia, hypoglycemia, and hyponatremia (800 mg/m2). The MTD was not reached. Two patients demonstrated complete response, three patients had partial response, and four patients had stable disease. Perfusion MRI revealed a significant relationship between the change in tumor relative cerebral blood flow (rCBF) from baseline and area under the plasma concentration versus time curve after 16 weeks of therapy.

Conclusion: Cilengitide is well tolerated to doses of 2,400 mg/m2, durable complete and partial responses were seen in this phase I study, and clinical response appears related to rCBF changes.

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Figures

Figure 1
Figure 1
The mean concentration time profiles for the various doses of cilengitide evaluated in the present study.
Figure 2
Figure 2. Relationship between dose and CL and Vss of cilengitide, respectively
The relationship between various doses of cilengitide and the pharmacokinetic parameters CL and Vss.
Figure 3
Figure 3
Relationship between pharmacokinetic and pharmacodynamic parameters: The percent of baseline rCBV (Top row) and rCBF (Bottom row) versus the Cmax (Right column) and AUC (Left column).
See this image and copyright information in PMC

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References

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