Intra-Arterial Melphalan (L-Phenylalanine Mustard) Administered in Conjunction With Osmotic Blood-Brain Barrier Disruption in Patients With Brain Malignancies: A Phase I Study
- Determine the maximum tolerated dose of intra-arterial melphalan when given in
combination with BBBD in patients with primary or metastatic CNS malignancy.
- Determine the toxic effects of melphalan given with BBBD in these patients.
- Determine, preliminarily, the efficacy of this regimen in these patients.
OUTLINE: This is a dose-escalation study of melphalan.
Patients receive intra-arterial mannitol with BBBD followed by intra-arterial melphalan over
10 minutes on days 1 and 2*. Treatment repeats every 4 weeks for up to 12 monthly courses in
the absence of disease progression or unacceptable toxicity .
NOTE: *Patients with gliomas localized to the posterior circulation (i.e., brain stem
gliomas) receive melphalan on day 1 only.
Cohorts of 3-6 patients receive escalating doses of melphalan until the maximum tolerated
dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2
of 6 patients experience dose-limiting toxicity.
After completion of study therapy, patients are followed every 3 months for 1 year; every 6
months for the next 2 years; then annually.
PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Maximum tolerated dose (MTD)of Melphalan as measured by NCI CTC v2 toxicities
MTD = dose of Melphalan that produces grade 3 neurotoxicity in 33% of subjects
Edward A. Neuwelt, MD
OHSU Knight Cancer Institute
United States: Institutional Review Board
|Knight Cancer Institute at Oregon Health and Science University||Portland, Oregon 97239-3098|