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

L. Burt Nabors, Tom Mikkelsen, Steven 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

Research output: Contribution to journalArticle

245 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1651-1657
Number of pages7
JournalJournal of Clinical Oncology
Volume25
Issue number13
DOIs
StatePublished - May 1 2007
Externally publishedYes

Fingerprint

Glioma
Cerebrovascular Circulation
Maximum Tolerated Dose
Magnetic Resonance Angiography
Cilengitide
Hyponatremia
Arthralgia
Anorexia
Hypoglycemia
Intravenous Infusions
Thrombocytopenia
Thrombosis
Therapeutics
Bone and Bones

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nabors, L. B., Mikkelsen, T., Rosenfeld, S., Hochberg, F., Akella, N. S., Fisher, J. D., ... Grossman, S. A. (2007). Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. Journal of Clinical Oncology, 25(13), 1651-1657. https://doi.org/10.1200/JCO.2006.06.6514

Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. / Nabors, L. Burt; Mikkelsen, Tom; Rosenfeld, Steven; Hochberg, Fred; Akella, Narasimha S.; Fisher, Joy D.; Cloud, Gretchen A.; Zhang, Yu; Carson, Kathryn; Wittemer, Sabine M.; Colevas, A. Dimitrios; Grossman, Stuart A.

In: Journal of Clinical Oncology, Vol. 25, No. 13, 01.05.2007, p. 1651-1657.

Research output: Contribution to journalArticle

Nabors, LB, Mikkelsen, T, Rosenfeld, S, Hochberg, F, Akella, NS, Fisher, JD, Cloud, GA, Zhang, Y, Carson, K, Wittemer, SM, Colevas, AD & Grossman, SA 2007, 'Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma', Journal of Clinical Oncology, vol. 25, no. 13, pp. 1651-1657. https://doi.org/10.1200/JCO.2006.06.6514
Nabors, L. Burt ; Mikkelsen, Tom ; Rosenfeld, Steven ; Hochberg, Fred ; Akella, Narasimha S. ; Fisher, Joy D. ; Cloud, Gretchen A. ; Zhang, Yu ; Carson, Kathryn ; Wittemer, Sabine M. ; Colevas, A. Dimitrios ; Grossman, Stuart A. / Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 13. pp. 1651-1657.
@article{83f323c49d9b4402b5eb3f60e0851e30,
title = "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 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.",
author = "Nabors, {L. Burt} and Tom Mikkelsen and Steven Rosenfeld and Fred Hochberg and Akella, {Narasimha S.} and Fisher, {Joy D.} and Cloud, {Gretchen A.} and Yu Zhang and Kathryn Carson and Wittemer, {Sabine M.} and Colevas, {A. Dimitrios} and Grossman, {Stuart A.}",
year = "2007",
month = "5",
day = "1",
doi = "10.1200/JCO.2006.06.6514",
language = "English (US)",
volume = "25",
pages = "1651--1657",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "13",

}

TY - JOUR

T1 - Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma

AU - Nabors, L. Burt

AU - Mikkelsen, Tom

AU - Rosenfeld, Steven

AU - Hochberg, Fred

AU - Akella, Narasimha S.

AU - Fisher, Joy D.

AU - Cloud, Gretchen A.

AU - Zhang, Yu

AU - Carson, Kathryn

AU - Wittemer, Sabine M.

AU - Colevas, A. Dimitrios

AU - Grossman, Stuart A.

PY - 2007/5/1

Y1 - 2007/5/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34249087162&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34249087162&partnerID=8YFLogxK

U2 - 10.1200/JCO.2006.06.6514

DO - 10.1200/JCO.2006.06.6514

M3 - Article

VL - 25

SP - 1651

EP - 1657

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 13

ER -