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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.