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.
authors.affiliation: Department of Neuro-Oncology, M.D. Anderson Cancer Center, University of Texas, Box 431, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
authors.forename: Lara J
authors.initials: LJ
authors.lastname: Kunschner
authors.forename: Howard
authors.initials: H
authors.lastname: Fine
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hess
authors.forename: Kurt
authors.initials: K
authors.lastname: Jaeckle
authors.forename: Athanassios P
authors.initials: AP
authors.lastname: Kyritsis
authors.forename: W K Alfred
authors.initials: WK
authors.lastname: Yung
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy*; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D005260:Female; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002219:Carbamates; D011719:Pyrazines; D011725:Pyridines; C072383:canertinib dihydrochloride