Melphalan With BBBD in Treating Patients With Brain Malignancies
RATIONALE: Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving drugs directly into the arteries around the tumor may kill more tumor cells. Mannitol may open the blood vessels around the brain [Blood-Brain Barrier Disruption (BBBD)]and allow melphalan to be carried directly to the brain tumor. Giving melphalan together with BBBD may be an effective treatment for central nervous system cancer.
PURPOSE: This phase I trial is studying side effects and best dose of melphalan when given together with mannitol in treating patients with central nervous system cancer.
Brain and Central Nervous System Tumors
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Intra-Arterial Melphalan (L-Phenylalanine Mustard) Administered in Conjunction With Osmotic Blood-Brain Barrier Disruption in Patients With Brain Malignancies: A Phase I Study|
- Maximum tolerated dose (MTD)of Melphalan as measured by NCI common toxicity criteria (CTC) v2 toxicities [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]MTD = dose of Melphalan that produces grade 3 neurotoxicity in 33% of subjects
- Efficacy of chemotherapy regimen as measured by clinical and radiographic response from first day of treatment [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||May 1998|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
|Experimental: All subjects||
All levels: Every 4 weeks for up to one year
Dose Escalation Plan:
Level 1: 4mg/m2/day x 2 days
Level 2: 6mg/m2/day x 2 days
Level 3: 8mg/m2/day x 2 days
Level 4: 10mg/m2/day x 2 days
Level 5: 12mg/m2/day x 2 days
- Determine the maximum tolerated dose of intra-arterial melphalan when given in combination with BBBD in patients with primary or metastatic central nervous system (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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00253721
|United States, Oregon|
|Knight Cancer Institute at Oregon Health and Science University|
|Portland, Oregon, United States, 97239-3098|
|Principal Investigator:||Edward A. Neuwelt, MD||OHSU Knight Cancer Institute|