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

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Duke University Identifier:
First received: November 1, 1999
Last updated: February 15, 2013
Last verified: February 2013

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.

Condition Intervention Phase
Brain and Central Nervous System Tumors
Drug: busulfan
Phase 1

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: Phase I Study of Intrathecal Spartaject-Busulfan in Patients With Neoplastic Meningitis

Resource links provided by NLM:

Further study details as provided by Duke University:

Estimated Enrollment: 20
Study Start Date: April 1998
Study Completion Date: February 2001
Primary Completion Date: February 2001 (Final data collection date for primary outcome measure)
Detailed Description:


  • 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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • 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)
  Contacts and Locations
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Please refer to this study by its identifier: NCT00003462

United States, North Carolina
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
National Cancer Institute (NCI)
Study Chair: Henry S. Friedman, MD Duke Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: Duke University Identifier: NCT00003462     History of Changes
Other Study ID Numbers: 0672, DUMC-0672-03-3R5, DUMC-000672-02-3R4, DUMC-000672-00-3R2, DUMC-000672-01-3R3, DUMC-0631-99-4RI, DUMC-625-98-4, DUMC-98045, DUMC-FDR001519, NCI-G98-1463, CDR0000066494
Study First Received: November 1, 1999
Last Updated: February 15, 2013
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Duke University:
leptomeningeal metastases

Additional relevant MeSH terms:
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Nervous System Diseases
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses processed this record on November 27, 2015