Busulfan in Treating Children and Adolescents With Refractory CNS Cancer

NCT ID: NCT00006246

Last Updated: 2009-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-11-30

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

PURPOSE: Phase I trial to study the safety of delivering intrathecal busulfan in children and adolescents who have refractory CNS cancer and to estimate the maximum tolerated dose of this treatment regimen.

Detailed Description

OBJECTIVES:

• Determine the qualitative and quantitative toxicities of intrathecally administered busulfan in children and adolescents with refractory CNS malignancies.
• Determine the maximum tolerated dose of this treatment regimen in these patients.
• Determine the cerebrospinal fluid and serum pharmacokinetics of this treatment regimen in these patients.
• Determine the efficacy of this treatment regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive intrathecal busulfan twice a week, at least 3 days apart, for 2 weeks. Patients with complete or partial response or stable disease may continue therapy once a week for 2 weeks, once a week every other week for 2 treatments, and then once a month thereafter in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of busulfan until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose limiting toxicities.

Patients are followed every 3 months for the first year, every 6 months for 4 years, and then annually for 5 years.

PROJECTED ACCRUAL: Approximately 18-24 patients will be accrued for this study over 18-38 months.

Conditions

Brain and Central Nervous System Tumors; Childhood Germ Cell Tumor; Leukemia; Lymphoma; Metastatic Cancer; Retinoblastoma; Sarcoma

Study Design

• Primary Study Purpose: TREATMENT

Interventions

busulfan

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed CNS malignancy, including any of the following:

• Primary malignant brain tumor refractory to standard therapy and metastatic to the cerebrospinal fluid (CSF) or leptomeningeal subarachnoid space
• Recurrent or persistent leptomeningeal leukemia, lymphoma, or germ cell tumor refractory to conventional therapy

• In second or greater relapse
• CSF white blood count greater than 5 cells/mm3 with blasts on cytospin OR
• Evidence of leptomeningeal tumor by MRI
• No concurrent bone marrow disease
• No obstruction or compartmentalization of CSF flow on CSF flow study

PATIENT CHARACTERISTICS:

Age:

• 3 to 21

Performance status:

• Lansky 50-100% (under 10 years)
• Karnofsky 50-100% (10 to 21 years)

Life expectancy:

• Greater than 8 weeks

Hematopoietic:

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 75,000/mm^3

Hepatic:

• Bilirubin normal for age
• ALT and AST less than 5 times upper limit of normal (ULN)
• No hepatic disease

Renal:

• Creatinine no greater than 1.5 times ULN OR
• Glomerular filtration rate greater than 70 mL/min
• No renal disease

Cardiovascular:

• No cardiac disease

Pulmonary:

• No pulmonary disease

Other:

• No uncontrolled infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• At least 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas)
• At least 1 week since prior intrathecal chemotherapy (2 weeks for cytarabine) and recovered
• Evidence of subsequent disease progression
• Concurrent systemic chemotherapy allowed for recurrent disease after first course of treatment except for the following:

• Chemotherapy targeted at leptomeningeal disease
• Other phase I agent
• Any agent that significantly penetrates the CSF (e.g., high dose methotrexate greater than 1 g/m2, thiotepa, high dose cytarabine, fluorouracil, IV mercaptopurine, nitrosoureas, or topotecan)
• Any agent that causes serious unpredictable CNS side effects

Endocrine therapy:

• Prior dexamethasone allowed with decreasing or stable dose at least one week before study
• Concurrent dexamethasone or prednisone with chemotherapy regimen allowed

Radiotherapy:

• At least 1 week since prior focal irradiation to the brain or spine
• At least 8 weeks since prior craniospinal irradiation
• No concurrent cranial or craniospinal irradiation

Surgery:

• Not specified

Other:

• No other concurrent intrathecal or systemic therapy for leptomeningeal disease

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Pediatric Brain Tumor Consortium

NETWORK

Sponsor Role: lead

Responsible Party

Pediatric Brain Tumor Consortium

Principal Investigators

Sri Gururangan, MD

Role: STUDY_CHAIR

Duke University

Locations

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Duke Comprehensive Cancer Center

Durham, North Carolina, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, United States

Countries

United States

References

Gururangan S, Petros WP, Poussaint TY, Hancock ML, Phillips PC, Friedman HS, Bomgaars L, Blaney SM, Kun LE, Boyett JM. Phase I trial of intrathecal spartaject busulfan in children with neoplastic meningitis: a Pediatric Brain Tumor Consortium Study (PBTC-004). Clin Cancer Res. 2006 Mar 1;12(5):1540-6. doi: 10.1158/1078-0432.CCR-05-2094.

Reference Type: RESULT

PMID: 16533779 (View on PubMed)

Other Identifiers

PBTC-004

Identifier Type: -

Identifier Source: secondary_id

CDR0000068178

Identifier Type: -

Identifier Source: org_study_id