Conditions: Central Nervous System Tumors
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 26
Healthy volunteers: no

Brief summary:
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.

Detailed description:
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.

Arms:
arm 1: Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m\^2 IV Temozolomide 75 mg/m\^2 PO arm 2: Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m\^2 IV Temozolomide 125 mg/m\^2 PO arm 3: Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m\^2 IV Temozolomide 175 mg/m\^2 PO arm 4: Bevacizmuab 10 mg/kg IV Irinotecan 125 mg/m\^2 IV Temozolomide 200 mg/m\^2 PO arm 5: Bevacizmuab 10 mg/kg IV Irinotecan 150 mg/m\^2 IV Temozolomide 200 mg/m\^2 PO

Interventions: intervention 1: Bevacizumab intervention 2: Irinotecan intervention 3: Temozolomide
Intervention descriptions: intervention 1: Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle intervention 2: 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. intervention 3: 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)

Protocol document: