CI-980 for the treatment of recurrent or progressive malignant gliomas

National Central Nervous System Consortium phase I-II evaluation of CI-980

Lara J. Kunschner, Howard Fine, Kenneth Hess, Kurt Jaeckle, Athanassios P. Kyritsis, W. K.Alfred Yung

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Objective: The purpose of this phase I/II trial was to determine the maximal tolerated dose of CI-980, and determine efficacy against malignant glioma. Background: The CI-980 is a synthetic mitosis inhibitor that acts via the colchicine binding site on tubulin. Broad in vitro activity has been seen in a variety of human and murine tumor models. Phase I studies have demonstrated schedule dependent toxicity of CI-980. Dose-limiting toxicity was neurologic when CI-980 was given as a 24-hr infusion and hematologic when given over 72 hr at higher doses. Methods: Twenty-four patients ages 29-65 entered this study. Six patients were treated on the phase I arm at three escalating dose levels ranging from 10.5 to 13.5 mg/m2, given over 72 hr. Eighteen patients were then treated at the highest tolerated dose, 13.5 mg/m2 per cycle. Treatment response was based on serial MRI imaging characteristics. Results: The phase II study was stopped at the end of the first stage due to poor treatment response. There were no partial or complete responses, (0/24) 95% CI = 0-14%. Four patients (4/24) had a best treatment response of stable disease/no change. Median time to progression for all patients was 6.4 weeks (95% CI: 6-9 weeks). Dose-limiting toxicity was grade 3-4 granulocytopenia. Three episodes of neurotoxicity manifested by a moderate cerebellar dysfunction were seen. Conclusions: These results fail to demonstrate the significant activity of CI-980 against recurrent glioma.

Original languageEnglish (US)
Pages (from-to)948-954
Number of pages7
JournalCancer Investigation
Volume20
Issue number7-8
DOIs
StatePublished - Nov 23 2002
Externally publishedYes

Fingerprint

Glioma
Central Nervous System
Cerebellar Diseases
Therapeutics
Agranulocytosis
Maximum Tolerated Dose
Colchicine
Tubulin
Mitosis
Nervous System
Appointments and Schedules
Binding Sites
canertinib dihydrochloride
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kunschner, Lara J. ; Fine, Howard ; Hess, Kenneth ; Jaeckle, Kurt ; Kyritsis, Athanassios P. ; Yung, W. K.Alfred. / CI-980 for the treatment of recurrent or progressive malignant gliomas : National Central Nervous System Consortium phase I-II evaluation of CI-980. In: Cancer Investigation. 2002 ; Vol. 20, No. 7-8. pp. 948-954.
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title = "CI-980 for the treatment of recurrent or progressive malignant gliomas: National Central Nervous System Consortium phase I-II evaluation of CI-980",
abstract = "Objective: The purpose of this phase I/II trial was to determine the maximal tolerated dose of CI-980, and determine efficacy against malignant glioma. Background: The CI-980 is a synthetic mitosis inhibitor that acts via the colchicine binding site on tubulin. Broad in vitro activity has been seen in a variety of human and murine tumor models. Phase I studies have demonstrated schedule dependent toxicity of CI-980. Dose-limiting toxicity was neurologic when CI-980 was given as a 24-hr infusion and hematologic when given over 72 hr at higher doses. Methods: Twenty-four patients ages 29-65 entered this study. Six patients were treated on the phase I arm at three escalating dose levels ranging from 10.5 to 13.5 mg/m2, given over 72 hr. Eighteen patients were then treated at the highest tolerated dose, 13.5 mg/m2 per cycle. Treatment response was based on serial MRI imaging characteristics. Results: The phase II study was stopped at the end of the first stage due to poor treatment response. There were no partial or complete responses, (0/24) 95{\%} CI = 0-14{\%}. Four patients (4/24) had a best treatment response of stable disease/no change. Median time to progression for all patients was 6.4 weeks (95{\%} CI: 6-9 weeks). Dose-limiting toxicity was grade 3-4 granulocytopenia. Three episodes of neurotoxicity manifested by a moderate cerebellar dysfunction were seen. Conclusions: These results fail to demonstrate the significant activity of CI-980 against recurrent glioma.",
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CI-980 for the treatment of recurrent or progressive malignant gliomas : National Central Nervous System Consortium phase I-II evaluation of CI-980. / Kunschner, Lara J.; Fine, Howard; Hess, Kenneth; Jaeckle, Kurt; Kyritsis, Athanassios P.; Yung, W. K.Alfred.

In: Cancer Investigation, Vol. 20, No. 7-8, 23.11.2002, p. 948-954.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CI-980 for the treatment of recurrent or progressive malignant gliomas

T2 - National Central Nervous System Consortium phase I-II evaluation of CI-980

AU - Kunschner, Lara J.

AU - Fine, Howard

AU - Hess, Kenneth

AU - Jaeckle, Kurt

AU - Kyritsis, Athanassios P.

AU - Yung, W. K.Alfred

PY - 2002/11/23

Y1 - 2002/11/23

N2 - Objective: The purpose of this phase I/II trial was to determine the maximal tolerated dose of CI-980, and determine efficacy against malignant glioma. Background: The CI-980 is a synthetic mitosis inhibitor that acts via the colchicine binding site on tubulin. Broad in vitro activity has been seen in a variety of human and murine tumor models. Phase I studies have demonstrated schedule dependent toxicity of CI-980. Dose-limiting toxicity was neurologic when CI-980 was given as a 24-hr infusion and hematologic when given over 72 hr at higher doses. Methods: Twenty-four patients ages 29-65 entered this study. Six patients were treated on the phase I arm at three escalating dose levels ranging from 10.5 to 13.5 mg/m2, given over 72 hr. Eighteen patients were then treated at the highest tolerated dose, 13.5 mg/m2 per cycle. Treatment response was based on serial MRI imaging characteristics. Results: The phase II study was stopped at the end of the first stage due to poor treatment response. There were no partial or complete responses, (0/24) 95% CI = 0-14%. Four patients (4/24) had a best treatment response of stable disease/no change. Median time to progression for all patients was 6.4 weeks (95% CI: 6-9 weeks). Dose-limiting toxicity was grade 3-4 granulocytopenia. Three episodes of neurotoxicity manifested by a moderate cerebellar dysfunction were seen. Conclusions: These results fail to demonstrate the significant activity of CI-980 against recurrent glioma.

AB - Objective: The purpose of this phase I/II trial was to determine the maximal tolerated dose of CI-980, and determine efficacy against malignant glioma. Background: The CI-980 is a synthetic mitosis inhibitor that acts via the colchicine binding site on tubulin. Broad in vitro activity has been seen in a variety of human and murine tumor models. Phase I studies have demonstrated schedule dependent toxicity of CI-980. Dose-limiting toxicity was neurologic when CI-980 was given as a 24-hr infusion and hematologic when given over 72 hr at higher doses. Methods: Twenty-four patients ages 29-65 entered this study. Six patients were treated on the phase I arm at three escalating dose levels ranging from 10.5 to 13.5 mg/m2, given over 72 hr. Eighteen patients were then treated at the highest tolerated dose, 13.5 mg/m2 per cycle. Treatment response was based on serial MRI imaging characteristics. Results: The phase II study was stopped at the end of the first stage due to poor treatment response. There were no partial or complete responses, (0/24) 95% CI = 0-14%. Four patients (4/24) had a best treatment response of stable disease/no change. Median time to progression for all patients was 6.4 weeks (95% CI: 6-9 weeks). Dose-limiting toxicity was grade 3-4 granulocytopenia. Three episodes of neurotoxicity manifested by a moderate cerebellar dysfunction were seen. Conclusions: These results fail to demonstrate the significant activity of CI-980 against recurrent glioma.

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SN - 0735-7907

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