Bevacizumab, irinotecan, and temozolomide are three agents shown to have promising activity in a variety of central nervous system tumors. No prospective studies have been published or are currently in progress within the major consortiums with this combination of drugs. Brain tumors are the second most common cause of cancer in pediatrics and the leading cause of cancer death in children. For children with High Grade Gliomas or with relapsed/refractory brain tumors, new agents in new combinations are needed. Historical data shows that newly diagnosed high grade gliomas 5 year progression free survival is 28-42%. Recurrent malignant gliomas median survival is 3-9 months. Recurrent medulloblastoma's 2 years survival is 9%. This study is a phase I study designed to provide an objective observation of toxicity and establish a maximum tolerated dose of this combination. In addition, this study will observe the response of children with relapsed or refractory central nervous system tumors.
Bevacizumab dosing is 10 mg/kg on day 1 and day 15 of a 28 days course given IV. Irinotecan dosing is 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels. If the MTD of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150 mg/m2. For dose level 0 Temozolomide, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO. Doses will be escalated according to standard phase I dose escalation criteria.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle
Irinotecan 125 mg/m2 on day 1 and day 15 of a 28 day course given IV for the first 3 dose levels. If the Maximum Tolerated Dose of temozolomide is not reached at dose level 3, then dose level 4 will be an escalation of irinotecan to 150mg/m2.
For the first cohort (dose level 0) of patients, dosing is 75 mg/m2/day day 1-5 of a 28 day course given PO for the first course. Doses will be escalated according to standard phase I dose escalation criteria. Dose levels are as follows (Dose level 1 = 125mg/m2, Dose level 2 = 175mg/m2, Dose levels 3 and 4 = 200 mg/m2)
Johns Hopkins All Children's Hospital
St. Petersburg, Florida, United States
Measurement of Number of Adverse Events
Collect and grade the all of the adverse events to evaluate for safety. This data was collected for the first 2 cycles for each participant.
Time frame: Two 28-day cycles
Best Response of Children With Recurrent or Refractory Central Nervous System Tumors With This Combination of Chemotherapy Agents.
Best response by MRIs per definitions in the protocol (complete response, partial response, stable disease, progressive disease). MRI's were obtained every 2 cycles and the best response was reported.
Time frame: Every 2 cycles up to 24 cycles
2 Year Event Free Survival With Children Treated With This Regimen.
2 year actual event free survival.with children treated with this protocol
Time frame: 2 year
To Provide Safety and Efficacy Data for to Recommend Further Larger Studies.
Number participants with grade 3 and 4 hematologic and non-hematologic toxicities. All toxicities are for end of cycle 2.
Time frame: Two 28 day cycles
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