NCT00876993

Study of Irinotecan and Bevacizumab With Temozolomide in Refractory/Relapsed Central Nervous System (CNS) Tumors

A Phase I Study Of Irinotecan and Bevacizumab With Temozolomide in Children With Recurrent/Refractory Central Nervous System Tumors

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 26 (actual)
• Sponsor: Johns Hopkins All Children's Hospital · Academic / Other
• Sex: All
• Age: 18 Months – 23 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Central Nervous System Tumors

Interventions

Type	Name	Description
DRUG	Bevacizumab	Bevacizumab 10 mg/kg IV on day 1 and day 15 of a 28 day cycle
DRUG	Irinotecan	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.
DRUG	Temozolomide	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)

Timeline

• Start date: 2008-09-01
• Primary completion: 2015-09-01
• Completion: 2015-09-01
• First posted: 2009-04-07
• Last updated: 2023-07-03
• Results posted: 2019-08-08

Locations

1 site across 1 country: United States