Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma.
Journal: 2007/May - Journal of Clinical Oncology
ISSN: 1527-7755
Abstract:
OBJECTIVE
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.
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.
CONCLUSIONS
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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J Clin Oncol 25(13): 101200/JCO.2006.06.6514.

A Phase I and Correlative Biology Study of Cilengitide in Patients with Recurrent Malignant Glioma

+3 authors
The trial was completed by the New Approaches to Brain Tumor Therapy (NABTT) CNS Consortium, University of Alabama at Birmingham, Birmingham, AL; Merck KGaA, Darmstadt, Germany, and Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD
Corresponding Author: L. Burt Nabors, M.D., c/o Joy D. Fisher, NABTT CNS Consortium, Cancer Research Building #2, 1550 Orleans Street – Room 1M-16, Baltimore, MD 21231, Phone: 410-955-8837 Fax: 410-614-9335 ude.imhj@rehsifj

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.

Abstract

Footnotes

This work has been presented in part at the Society of Neuro oncology Annual Meeting 2004.

Footnotes

References

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