Katja[a]
A phase I trial of CC-5103, a potent thalidomide analog, in patients with recurrent high-grade gliomas and other refractory CNS malignancies
Author(s): H. A. Fine, L. Kim, C. Royce, J. P. Duic, L. J. Cohen, S. Mitchell; National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD; Celgene Corp., Warren, NJ
CC-5013 [3-(4´aminoisoindoline-1´-one)-1-piperidine-2, 6-dione] is an analog of thalidomide with pharmacological and biological properties similar to thalidomide, but significantly more potent. Thalidomide, an inhibitor of angiogenesis, appears to have biologic activity in malignant gliomas although that activity may be too small to be clinically useful as a single agent. We have initiated a phase I dose-escalation trial of CC-5013 in adults with recurrent high-grade gliomas and other refractory central nervous system malignancies. Treatment consists of CC-5013 tablets administered once per day for 21 days on a 28 day cycle after which patients undergo a complete physical/neurological, biochemical and radiographic (MRI) re-evaluation. To date 20 patients have been accrued to the trial including 18 patients with recurrent high-grade gliomas, 1 patient with recurrent atypical meningioma, and one patient with multiple recurrent spinal hemangioblastomas. Treatment with CC-5013 has been very well tolerated with only one clear episode of drug-related toxicity > grade 1 (grade 2 myelosuppression in a patient with a prior bone marrow transplant). No sedation, constipation, peripheral neuropathy, or skin rash, common side effects of thalidomide treatment, have been observed to date. The one patient with rapidly progressive spinal hemangioblastomas and two patients with rapidly progressive glioblastoma treated with CC-5013 had disease stabilization for 6, 5 and 7 months respectively. A number of other patients continue treatment with CC-5013 and the trial continues to accrue additional patients in an attempt to determine the maximally tolerated dose. Completed results of the trial including angiogenic imaging studies (i.e. MRI perfusion, PET scans) will be presented at ASCO.
ASCO2003, Abstract No: 418 Category: CNS Tumors