Study of Busulfan for Refractory Central Nervous System (CNS) Tumors
Recruitment status was Not yet recruiting
This protocol is aimed at establishing a maximum tolerated dose (MTD) for submyeloablative doses of Busulfex ® with the hope that a tolerable, submyeloablative dose can be established to test efficacy as alternative therapy for refractory pediatric brain tumors.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study Using Submyeloablative DOsing of Intravenous Busulfan (Busulfex) for Refractory Brain Tumors|
- maximum tolerated dose (MTD) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- To describe the plasma pharmacokinetics in children with refractory barin tumors [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Event Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Experimental: IV Busulfan
This is a single arm study. All subjects will receive the study medication at varying doses to be determined by dose escalation.
Busulfex ® will be administered every 4 weeks (28 days) as a continuous 24 hour infusion for up to 6 courses. Given the inter-patient variation in drug excretion and resultant plasma concentration, dose escalation will be based on plasma concentration. The starting Busulfex ® plasma concentration will be 300 ng/mL. There are a total of 7 dose levels (-1 to 5). This study will start at dose level 1.
Other Name: Busulfex
Pediatric brain tumors remain among the most common malignancies in childhood, second only to leukemia, representing 20% of all childhood cancers in the United States (1). Although significant strides have been made in therapies for other pediatric malignancies, mortality for patients with brain tumors remains high. The mainstay of therapy for CNS tumors has been a combination of surgery, chemotherapy, and radiation. High dose chemotherapy with stem cell transplant has been proposed as an alternative to radiation, in very young children and for relapsed patients. Stem cell transplantation however is not without significant side effects as well as transplant related mortality.
Busulfan is an alkylating agent and is able to exert its cytotoxic effects through hydrolysis and subsequent production of carbonium ions, directly alkylating DNA, interfering with its replication, and ultimately leading to cell death (2). Busulfan readily crosses the blood barrier, allowing for CNS levels nearly equal to those of plasma levels (5,6).
To determine the maximum tolerated dose (MTD) of Busulfex ® in children with recurrent, progressive, or refractory primary brain tumors.
To obtain preliminary data regarding progression free survival (PFS) and event free survival (EFS) when Busulfex ® is used at submyeloablative doses in children with recurrent, progressive, or refractory primary brain tumors.
To describe the plasma pharmacokinetics of Busulfex ® in children with recurrent, progressive, or refractory primary brain tumors, using a continuous infusion.
|Contact: Molly Fouts, BS, CCRPfirstname.lastname@example.org|
|Contact: Carrie Kempler, MPH, CCRPemail@example.com|
|United States, Illinois|
|Children's Memorial Hospital||Not yet recruiting|
|Chicago, Illinois, United States, 60614|
|Contact: Molly Fouts, BS, CCRP 773-880-8147 firstname.lastname@example.org|
|Principal Investigator: Stewart Goldman, MD|
|Principal Investigator:||Stewart Goldman, MD||Ann & Robert H Lurie Children's Hospital of Chicago|