- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00836628
Study of Busulfan for Refractory Central Nervous System (CNS) Tumors
A Phase I Study Using Submyeloablative DOsing of Intravenous Busulfan (Busulfex) for Refractory Brain Tumors
Study Overview
Detailed Description
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).
Primary Objectives:
To determine the maximum tolerated dose (MTD) of Busulfex ® in children with recurrent, progressive, or refractory primary brain tumors.
Secondary Objectives:
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
Phase
- Phase 1
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
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
- Must be ≥ 3 weeks from myelosuppressive chemotherapy (6 weeks from nitrosoureas) and have demonstrated recovery (ANC ≥ 1000/uL) from their last course of chemotherapy
- ≥ 6 months following allogeneic stem cell transplantation
- ≥ 3 months following autologous stem cell transplantation
- ≥ 3 months from craniospinal radiation
- ≥ 4 weeks from focal radiation
- ≥ 7 days from any past biologic/immunotherapy
- ≥ 1 week from any hematopoietic growth factors Concomitant Medication
- Patients taking Itraconazole or Phenytoin will be excluded. Patients must be off of these medications for at least 3 days prior to entering this trial. If the patient is taking phenytoin for seizures at the time of study enrollment, it must be stopped at least 3 days prior to starting therapy and Clonazepam will be substituted during the Busulfex ® infusions and for 24 hours following the infusion.
- Patients on growth stimulating factors, such as GCSF, will be allowed to continue these medications only as indicated in the study.
- Patients may be taking steroids while participating in this trial, but should be on a stable dose for >1 week prior to enrollment.
- Medications interacting with the CYP3A4 substrate should also be avoided while the patient is on study.
- Patients should also be on Pneumocystis prophylaxis while participating in this study. Pentamidine will be required, with a recommended dose of 4 mg/kg given intravenously every month. Pentamidine should continue throughout the duration of the trial.
Organ Function Requirements Adequate Bone Marrow Function Defined As
- Peripheral absolute neutrophil count (ANC) greater than or equal to 1000/ul (off growth factors x 48 hrs)
- Platelet count greater than or equal to 100,000/uL (transfusion independent)
- Hemoglobin greater than or equal to 8.0 gm/dL (may receive RBC transfusions) Adequate Renal Function Defined As
- Serum creatinine less than or equal to 1.5 x upper limit of normal, or
- Estimated creatinine clearance GFR greater than or equal to 70 ml/min/1.73 m² by the Schwartz formula Adequate Liver Function Defined As
- Total bilirubin within normal range
- SGPT (ALT) within normal range Adequate Pulmonary Function Defined As
- Oxygen saturation >92% on room air Central Nervous System Function Defined As
- Patients with seizure disorder may be enrolled; Patients MUST be on an anti-seizure medication upon enrollment, but this medication CANNOT be phenytoin or carbamezepine.
- Patients must not be in status, coma or assisted ventilation prior to study enrollment.
- Stable neurologic exam of at least 1 week duration Performance Level Karnofsky/ Lansky 50 or greater
Exclusion Criteria:
- Pregnancy/Contraception: patients who are pregnant or breast-feeding will not be eligible.
- Patients of childbearing potential must practice an effective method of birth control while participating on the study.
- Females > 13 years of age or those who have achieved menarche must have a negative pregnancy test prior to study entry.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: experimental
|
Other Names:
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Brain Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neoplasms
- Neoplasms by Site
- Central Nervous System Neoplasms
- Nervous System Neoplasms
- Brain 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
- CNS 1100
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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