Phase I Dose Escalation Study of N-Acetylcysteine Administered in Conjunction With Carboplatin, Cyclophosphamide, and Etoposide Phosphate BBBD, in Children With Malignant Brain Tumors
- Determine the toxicity and maximum tolerated dose of acetylcysteine when given in
combination with blood-brain barrier disruption treatment with mannitol, combination
chemotherapy comprising cyclophosphamide, etoposide phosphate, and carboplatin, and
delayed high-dose sodium thiosulfate in pediatric patients with malignant brain tumors.
- Determine the blood/bone marrow toxicity of this regimen in these patients.
- Determine tumor response in patients treated with this regimen.
OUTLINE: This is a dose-escalation study of acetylcysteine.
Patients receive acetylcysteine IV over 30-60 minutes followed, at least 15 minutes later,
by x-ray-guided femoral artery catheterization under general anesthesia on days 1 and 2.
After placement of the catheter, patients receive cyclophosphamide IV over 10 minutes,
etoposide phosphate IV over 10 minutes, mannitol intra-arterially (IA) over 30 seconds, and
carboplatin IA over 10 minutes also on days 1 and 2. Patients then receive high-dose sodium
thiosulfate IV over 15 minutes 4 hours after completion of carboplatin. Some patients may
receive a second dose of sodium thiosulfate 8 hours after completion of carboplatin.
Beginning 48 hours after the last dose of chemotherapy on day 2, patients receive filgrastim
(G-CSF) subcutaneously once daily for 7-10 days or until blood counts recover. Treatment
repeats every 4 weeks for up to 12 courses in the absence of disease progression or
Cohorts of 3-6 patients receive escalating doses of acetylcysteine 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. An additional 3 patients are treated at the
After completion of study treatment, patients are followed periodically.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
To assess toxicity and the maximally tolerated dose of N-acetylcysteine administered in conjunction with carboplatin, cyclophosphamide and etoposide phosphate BBBD, and delayed high dose sodium thiosulfate, in children with malignant brain tumors.
Edward A. Neuwelt, MD
OHSU Knight Cancer Institute
United States: Federal Government
|OHSU Knight Cancer Institute||Portland, Oregon 97239|