This study seeks to determine the optimum dose frequency of 5-Azacytidin (5-AZA) infusions into the fourth ventricle of the brain. The study's primary objective is to establish the maximum tolerated dose for infusions of 5-Azacytidine into the fourth ventricle in patients with recurrent ependymoma. The study's secondary objective is to assess the antitumor activity of 5-Azacytidine infusions into the fourth ventricle based upon imaging studies and cytology.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
3
5-AZA (12 mg) will be prepared in preservative-free normal saline to a total volume of 1.2ml. 5-AZA will be infused over a minimum of 30 seconds. 5-AZA will be followed by a 1 ml preservative-free normal saline flush over a minimum of 30 seconds. Patients will receive two, three, or four 5-AZA infusions per week depending on the dosing algorithm (see below). We refer to these dosing schedules as dose 1, 2, or 3. Patients assigned to dose 1 will receive two 5-AZA infusions per week (typically Monday and Thursday but may be given on other days based upon logistical considerations) for 8 consecutive weeks.
5-AZA (12 mg) will be prepared in preservative-free normal saline to a total volume of 1.2ml. 5-AZA will be infused over a minimum of 30 seconds. 5-AZA will be followed by a 1 ml preservative-free normal saline flush over a minimum of 30 seconds. Patients will receive two, three, or four 5-AZA infusions per week depending on the dosing algorithm (see below). We refer to these dosing schedules as dose 1, 2, or 3. Patients assigned to dose 2 will receive three 5-AZA infusions per week (typically Monday, Wednesday, and Friday but may be given on other days based upon logistical considerations) for 8 consecutive weeks.
The University of Texas Health Science Center at Houston
Houston, Texas, United States
Number of participants who experienced dose-limiting toxicity (DLT)
Dose-limiting toxicity will be defined as any of the following events: New neurological deficit (grade 3 or higher) probably or definitely attributed to intraventricular 5-azacytidine infusions. New adverse event involving any organ probably or definitely attributed to intraventricular 5-azacytidine infusions with the specific exclusion of: Grade 3 or higher nausea and vomiting \< 3 days duration and grade 3 or higher headache \< 3 days duration.
Time frame: 8 weeks
Number of participants with disease progression as assessed by magnetic resonance imaging (MRI)
The PI and radiologist will determine Response to treatment according to the following three categories. Disease progression corresponds with the "Progressive Disease" category. Complete Response (CR): Disappearance of all non-target lesions. Stable Disease (SD) / Incomplete Response (IR): The persistence of one or more non-target lesions. Progressive Disease (PD): The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: 1 day after surgery to remove tumor (which is about 1 week before the first infusion)
Number of participants with disease progression as assessed by magnetic resonance imaging (MRI)
The PI and radiologist will determine Response to treatment according to the following three categories. Disease progression corresponds with the "Progressive Disease" category. Complete Response (CR): Disappearance of all non-target lesions. Stable Disease (SD) / Incomplete Response (IR): The persistence of one or more non-target lesions. Progressive Disease (PD): The appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: 8 weeks after first infusion
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5-AZA (12 mg) will be prepared in preservative-free normal saline to a total volume of 1.2ml. 5-AZA will be infused over a minimum of 30 seconds. 5-AZA will be followed by a 1 ml preservative-free normal saline flush over a minimum of 30 seconds. Patients will receive two, three, or four 5-AZA infusions per week depending on the dosing algorithm (see below). We refer to these dosing schedules as dose 1, 2, or 3. Patients assigned to dose 3 will receive four 5-AZA infusions per week (on any 4 weekdays based upon logistical considerations) for 8 consecutive weeks.