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

NCT ID: NCT00003462

Last Updated: 2013-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-04-30
• Study Completion Date: 2001-02-28

Brief 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.

Detailed 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.

Conditions

Brain and Central Nervous System Tumors

Study Design

• Primary Study Purpose: TREATMENT

Interventions

busulfan

Intervention Type: DRUG

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Henry S. Friedman, MD

Role: STUDY_CHAIR

Duke Cancer Institute

Locations

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Countries

United States

Other Identifiers

DUMC-0672-03-3R5

Identifier Type: -

Identifier Source: secondary_id

DUMC-000672-02-3R4

Identifier Type: -

Identifier Source: secondary_id

DUMC-000672-00-3R2

Identifier Type: -

Identifier Source: secondary_id

DUMC-000672-01-3R3

Identifier Type: -

Identifier Source: secondary_id

DUMC-0631-99-4RI

Identifier Type: -

Identifier Source: secondary_id

DUMC-625-98-4

Identifier Type: -

Identifier Source: secondary_id

DUMC-98045

Identifier Type: -

Identifier Source: secondary_id

DUMC-FDR001519

Identifier Type: -

Identifier Source: secondary_id

NCI-G98-1463

Identifier Type: -

Identifier Source: secondary_id

CDR0000066494

Identifier Type: OTHER

Identifier Source: secondary_id

0672

Identifier Type: -

Identifier Source: org_study_id