Intrathecal Busulfan in Treating Patients With Recurrent, Refractory, or Metastatic Leptomeningeal Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00003462
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : February 20, 2013
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Duke University

November 1, 1999
January 27, 2003
February 20, 2013
April 1998
February 2001   (Final data collection date for primary outcome measure)
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Complete list of historical versions of study NCT00003462 on Archive Site
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Intrathecal Busulfan in Treating Patients With Recurrent, Refractory, or Metastatic Leptomeningeal Tumors
Phase I Study of Intrathecal Spartaject-Busulfan in Patients With Neoplastic Meningitis

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Giving drugs into the thin space between the lining of the spinal cord and brain may kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of intrathecal busulfan in treating patients with recurrent, refractory, or metastatic leptomeningeal tumors.


  • 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.

Phase 1
Primary Purpose: Treatment
Brain and Central Nervous System Tumors
Drug: busulfan
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*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
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February 2001
February 2001   (Final data collection date for primary outcome measure)


  • 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



  • 18 and over

Performance status:

  • Karnofsky 60-100%

Life expectancy:

  • At least 8 weeks


  • Absolute neutrophil count greater than 1,500/mm^3
  • Platelet count greater than 100,000/mm^3


  • Bilirubin less than 2.5 mg/dL
  • SGOT or SGPT less than 1.5 times normal


  • BUN less than 30 mg/dL
  • Creatinine less than 1.5 mg/dL
  • Calcium within normal limits


  • Neurological examination stable
  • No rapidly progressing or deteriorating neurological deficits


  • No active infectious process
  • Magnesium, phosphorus, potassium, chloride, and bicarbonate normal
  • Not pregnant or nursing
  • Fertile patients must use effective contraception


Biologic therapy:

  • At least 4 weeks since prior immunotherapy


  • 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


  • 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


  • At least 3 weeks since prior surgery


  • No concurrent medication that may interfere with study results (e.g., immunosuppressive agents other than corticosteroids)
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
United States
CDR0000066494 ( Other Identifier: NCI )
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Duke University
Duke University
National Cancer Institute (NCI)
Study Chair: Henry S. Friedman, MD Duke Cancer Institute
Duke University
February 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP