phase I trial of CC-5103, a potent thalidomide analog, in patients with
recurrent high-grade gliomas and other refractory CNS malignancies
A. Fine, L. Kim, C. Royce, J. P. Duic, L. J. Cohen, S. Mitchell
Cancer Institute, National Institute of Neurological Disorders and Stroke,
National Institutes of Health, Bethesda, MD; Celgene Corp., Warren, NJ
[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
Completed results of the trial including angiogenic imaging studies (i.e. MRI
perfusion, PET scans) will be presented at ASCO.
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American Society of Clinical Oncology All rights