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

Brain and Central Nervous System Tumors Clinical Trial

Official title:

Phase I Study of Intrathecal Spartaject-Busulfan in Patients With Neoplastic Meningitis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00003462
• Other study ID #: 0672
• Secondary ID: DUMC-0672-03-3R5
• Status: Completed
• Phase: Phase 1
• First received: November 1, 1999
• Last updated: February 15, 2013
• Start date: April 1998
• Est. completion date: February 2001

Study information

• Verified date: February 2013
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: February 2001
• Est. primary completion date: February 2001
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Central Nervous System Neoplasms
• Nervous System Neoplasms

Intervention

Drug:
• busulfan

Locations

Country	Name	City	State
United States	Duke Comprehensive Cancer Center	Durham	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States,