Phase II Study of Bevacizumab Plus Irinotecan (Camptosar™) in Children With Recurrent, Progressive, or Refractory Malignant Gliomas, Diffuse/Intrinsic Brain Stem Gliomas, Medulloblastomas, Ependymomas and Low Grade Gliomas
OBJECTIVES:
Primary
- Estimate the rates of objective response observed prior to disease progression during
the first four courses of treatment with bevacizumab and irinotecan hydrochloride in
pediatric patients with recurrent, progressive, or refractory malignant glioma (Stratum
A [closed to accrual as of 4/21/2009]) or recurrent/progressive/refractory intrinsic
brain stem glioma (Stratum B [closed to accrual as of 4/21/2009]).
- Estimate the rates of objective response observed prior to disease progression during
the first four courses of treatment with bevacizumab and irinotecan hydrochloride in
patients with recurrent or progressive medulloblastoma (Stratum C [closed to accrual as
of 10/27/2009]) or recurrent or progressive ependymoma (Stratum D [closed to accrual as
of 7/29/2010]).
- Estimate the sustained disease stabilization rate associated with bevacizumab and
irinotecan in patients with recurrent or progressive low grade glioma (Stratum E
[closed to accrual as of 7/29/2010]).
Secondary
- Estimate the rate of treatment-related toxicity of this regimen in these patients.
- Estimate the cumulative incidence of sustained objective responses as a function of
this regimen in these patients.
- Estimate the distributions of survival and event-free survival of these patients.
- Correlate functional changes in tumor with progression-free survival and response using
MR perfusion/diffusion imaging and fludeoxyglucose F 18 positron emission tomography.
OUTLINE: This is a multicenter study. Patients are stratified according to tumor type
(high-grade glioma [closed to accrual as of 4/21/2009] vs intrinsic brain stem tumor [closed
to accrual as of 4/21/2009] vs medulloblastoma [closed to accrual as of 10/27/2010] vs
ependymoma [closed to accrual as of 7/29/2010] vs low grade glioma [closed to accrual as of
7/29/2010]).
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and irinotecan
hydrochloride IV over 90 minutes on day 16 or 17 for course 1. Patients receive bevacizumab
and irinotecan hydrochloride on days 1 and 15 for all subsequent courses. Treatment repeats
every 4 weeks for up to 24 courses in the absence of disease progression or unacceptable
toxicity.
Patients undergo MRIs of the brain, magnetic resonance perfusion/diffusion, and
fludeoxyglucose F 18 positron emission tomography at baseline and periodically during
treatment.
After completion of study treatment, patients are followed for 30 days and then every 3
months for up to 2 years.
PROJECTED ACCRUAL: A total of 140 patients will be accrued for this study.
Interventional
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Objective Response Rate Sustained for ≥ 8 Weeks
Objective response is either a complete response or a partial response observed during the first four courses of treatment and sustained for 8 weeks. The objective response rate will be reported separately for patients with recurrent/progressive malignant glioma(Stratum A), recurrent/progressive instrinsic brain stem tumors(Stratum B), recurrent/progressive medulloblastoma(Stratum C), and recurrent/progressive ependymoma(Stratum D). CR is complete disappearance of all enhancing tumor. PR is >= 50% reduction in tumor size. This outcome measures is not defined for the Stratum E in the protocol.
From day 1 of treatment up to 24 weeks
No
Sri Gururangan, MD
Study Chair
Duke University
United States: Food and Drug Administration
NCI-2009-01090
NCT00381797
August 2006
July 2015
Name | Location |
---|---|
Children's Hospital of Philadelphia | Philadelphia, Pennsylvania 19104 |
Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
Children's National Medical Center | Washington, District of Columbia 20010-2970 |
Children's Hospital of Pittsburgh | Pittsburgh, Pennsylvania 15213 |
Children's Memorial Hospital - Chicago | Chicago, Illinois 60614 |
St. Jude Children's Research Hospital | Memphis, Tennessee 38105-2794 |
UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
Dan L. Duncan Cancer Center at Baylor College of Medicine | Houston, Texas 77030 |