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.

Study Overview

• Status: Completed
• Conditions: Brain and Central Nervous System Tumors
• Intervention / Treatment: Drug: busulfan

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.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: April 1, 1998
• Primary Completion (Actual): February 1, 2001
• Study Completion (Actual): February 1, 2001

Study Registration Dates

• First Submitted: November 1, 1999
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): February 20, 2013
• Last Update Submitted That Met QC Criteria: February 15, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: leptomeningeal metastases
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms; Neoplasms by Site; Nervous System Neoplasms; Central Nervous System Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Busulfan
• 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 (Other Identifier: NCI)