Study of Busulfan for Refractory Central Nervous System (CNS) Tumors
Recruitment status was Not yet recruiting
|First Received Date ICMJE||February 3, 2009|
|Last Updated Date||February 3, 2009|
|Start Date ICMJE||Not Provided|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
||maximum tolerated dose (MTD) [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]|
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Study of Busulfan for Refractory Central Nervous System (CNS) Tumors|
|Official Title ICMJE||A Phase I Study Using Submyeloablative DOsing of Intravenous Busulfan (Busulfex) for Refractory Brain Tumors|
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.
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.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 1|
|Study Design ICMJE||Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||Refractory Brain Tumors|
|Intervention ICMJE||Drug: Busulfan
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
|Study Arm (s)||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.
Intervention: Drug: Busulfan
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Not yet recruiting|
|Estimated Enrollment ICMJE||20|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Age: Age >2 year and ≤ 21 years Histologic Diagnosis Any histological proven (confirmed by institutional pathology report; pathology slides from outside referring outside institutions are not required.) recurrent or progressive CNS tumor. (optic pathway and brainstem gliomas allowed without histologic verification, but must have diagnostic imaging).
Life Expectancy Patients must have a life expectancy of ≥ 2 months. Prior Therapy There is no limit to the number of prior therapies a patient has received
Organ Function Requirements Adequate Bone Marrow Function Defined As
|Ages||3 Years to 21 Years|
|Accepts Healthy Volunteers||No|
|Location Countries ICMJE||United States|
|NCT Number ICMJE||NCT00836628|
|Other Study ID Numbers ICMJE||CNS 1100|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Stewart Goldman, MD, Director, Neuro-Oncology, Children's Memorial Hospital|
|Study Sponsor ICMJE||Ann & Robert H Lurie Children's Hospital of Chicago|
|Collaborators ICMJE||Not Provided|
|Information Provided By||Ann & Robert H Lurie Children's Hospital of Chicago|
|Verification Date||February 2009|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP