Phase I Study of Intrathecal Spartaject-Busulfan in Patients With Neoplastic Meningitis
18 Years
N/A
Both
Brain and Central Nervous System Tumors
Trial Information
Phase I Study of Intrathecal Spartaject-Busulfan in Patients With Neoplastic Meningitis
OBJECTIVES:
- Determine the maximum tolerated dose of intrathecal busulfan by a limited escalation
dosage schedule in patients with recurrent or refractory leptomeningeal tumors.
- Determine the cerebrospinal fluid and serum pharmacokinetics of busulfan administered
via intralumbar or intraventricular routes in these patients.
OUTLINE: This is dose-escalation study.
Patients receive intrathecal busulfan via intralumbar or intraventricular routes twice a
week for 2 weeks (4 treatments). Any patient with objective or significant clinical response
may continue treatment by receiving the same dose once a week for 2 consecutive weeks, once
a week every other week for 3 weeks (2 treatments), and then once a month thereafter until
disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of intrathecal busulfan 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.
Patients are followed every 12 weeks for 1 year or until disease progression.
PROJECTED ACCRUAL: A total of 5-20 patients will be accrued for this study within 1-2 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed neoplasm that is metastatic in the cerebrospinal fluid or
leptomeningeal/subarachnoid space
- Cytologic diagnosis of malignancy in the cerebrospinal fluid or neuroimaging
evidence of leptomeningeal tumor by MRI
- Must have a recurrent or refractory leptomeningeal tumor
- Leptomeningeal tumors of leukemia, lymphoma, and all germ cell tumors must have
also failed initial treatment or be recurrent
- No evidence of obstructive hydrocephalus or complete block of the spinal
cerebrospinal fluid pathways on prestudy technetium Tc 99m albumin or indium In 111
DTPA flow study
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Karnofsky 60-100%
Life expectancy:
- At least 8 weeks
Hematopoietic:
- Absolute neutrophil count greater than 1,500/mm^3
- Platelet count greater than 100,000/mm^3
Hepatic:
- Bilirubin less than 2.5 mg/dL
- SGOT or SGPT less than 1.5 times normal
Renal:
- BUN less than 30 mg/dL
- Creatinine less than 1.5 mg/dL
- Calcium within normal limits
Neurological:
- Neurological examination stable
- No rapidly progressing or deteriorating neurological deficits
Other:
- No active infectious process
- Magnesium, phosphorus, potassium, chloride, and bicarbonate normal
- Not pregnant or nursing
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- At least 4 weeks since prior immunotherapy
Chemotherapy:
- At least 6 weeks since prior nitrosoureas or mitomycin
- At least 4 weeks since any other prior chemotherapy
- At least 3 weeks since prior intrathecal chemotherapy
- No other concurrent intrathecal chemotherapy
Endocrine therapy:
- For patients on corticosteroids:
- Must be on a stable dose of corticosteroids for at least 1 week
Radiotherapy:
- At least 3 weeks since prior radiotherapy to the CNS
- At least 4 weeks since any other prior radiotherapy
- No concurrent radiotherapy to the CNS
Surgery:
- At least 3 weeks since prior surgery
Other:
- No concurrent medication that may interfere with study results (e.g.,
immunosuppressive agents other than corticosteroids)
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Henry S. Friedman, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Duke Cancer Institute
Authority:
United States: Federal Government
Study ID:
0672
NCT ID:
NCT00003462
Start Date:
April 1998
Completion Date:
February 2001
Related Keywords:
- Brain and Central Nervous System Tumors
- leptomeningeal metastases
- Nervous System Neoplasms
- Central Nervous System Neoplasms
Name | Location |
|---|---|
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
