A Phase I and Correlative Biology Study of Cilengitide in Patients with Recurrent Malignant Glioma
Abstract
Purpose
This multi-institutional phase I trial was designed to determine the maximum tolerated dose (MTD) of cilengitide (EMD 121974) and evaluate the use of perfusion 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 was defined as any grade 3 or 4 non-hematological toxicity or grade 4 hematological toxicity of any duration.
Results
A total of 51 patients were enrolled in cohorts of 6 patients to doses of 120, 240, 360, 480, 600, 1200, 1800, and 2400 mg/m administered as a twice weekly intravenous infusion. Three patients progressed early and were inevaluable for toxicity assessment. The dose limiting toxicities observed were: one thrombosis (120 mg/m), one grade 4 joint and bone pain (480 mg/m), one thrombocytopenia (600 mg/m) and one anorexia, hypoglycemia, hyponatremia (800 mg/m). 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.
Conclusions
1) Cilengitide is well tolerated to doses of 2400 mg/m; 2) Durable complete and partial responses were seen in this phase I study; 3) Clinical response appears related to rCBF changes.
Footnotes
This work has been presented in part at the Society of Neuro oncology Annual Meeting 2004.
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