Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma.
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.
Nabors
L Burt
LB
New Approaches to Brain Tumor Therapy CNS Consortium, Baltimore, MD 21231, USA.
Mikkelsen
Tom
T
Rosenfeld
Steven S
SS
Hochberg
Fred
F
Akella
Narasimha S
NS
Fisher
Joy D
JD
Cloud
Gretchen A
GA
Zhang
Yu
Y
Carson
Kathryn
K
Wittemer
Sabine M
SM
Colevas
A Dimitrios
AD
Grossman
Stuart A
SA
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015331:Cohort Studies; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D020714:Maximum Tolerated Dose; D012008:Recurrence; D012910:Snake Venoms / Q000009:adverse effects / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D012910:Snake Venoms; C422910:Cilengitide