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 - 2002

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

Keywords

  • Chemotherapy
  • CI-980
  • Malignant gliomas

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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, 2002, p. 948-954.

Research output: Contribution to journalArticle

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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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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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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