A Phase I/II Study of ATN-161 and Carboplatin in Adult Patients With Recurrent Intracranial Malignant Glioma
- Establish the safety of ATN-161 and carboplatin in patients with recurrent intracranial
- Determine the maximum tolerated dose of ATN-161 when administered with carboplatin in
these patients. (phase I)
- Determine the antitumor activity of ATN-161 when administered with carboplatin in these
patients. (phase II)
- Describe the effects of this regimen on potential biomarkers of activity, including
functional imaging with brain perfusion scans and circulating endothelial progenitor
- Obtain preliminary evidence of efficacy of this regimen in these patients. (phase I)
- Characterize the plasma concentrations of this regimen in these patients. (phase I)
OUTLINE: This is an open-label, phase I dose-escalation study of ATN-161 followed by a phase
II study. Patients in the phase II portion of the study are stratified according to tumor
type (glioblastoma multiforme vs anaplastic glioma).
- Phase I: Patients receive ATN-161 IV over 10 minutes 3 times weekly in weeks 1-6 and
carboplatin IV over 20 minutes in week 3 during course 1. Beginning in course 2,
patients receive carboplatin IV over 20 minutes in week 1 and ATN-161 IV over 10
minutes 3 times weekly in weeks 1-4. Treatment repeats every 4 weeks in the absence of
disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of ATN-161 until the maximum tolerated dose
(MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients
experience dose-limiting toxicity during the first 6 weeks of treatment.
- Phase II: Patients receive carboplatin IV in week 1 and ATN-161 IV, at the MTD
determined in phase I, 3 times weekly in weeks 1-4. Treatment repeats every 4 weeks for
up to 12 courses in the absence of disease progression or unacceptable toxicity.
Patients undergo blood collection at baseline and then periodically during phase I course 1
for pharmacokinetic and pharmacodynamic analysis and at baseline and then periodically
during study for biomarker (e.g., circulating endothelial progenitor cells) correlative
After completion of study treatment, patients are followed for 28 days.
PROJECTED ACCRUAL: A total of 82 patients will be accrued for this study.
Masking: Open Label, Primary Purpose: Treatment
Howard A. Fine, MD
NCI - Neuro-Oncology Branch
United States: Food and Drug Administration
|Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office||Bethesda, Maryland 20892-1182|