Phase II Study of Bevacizumab Plus Irinotecan and Carboplatin for Recurrent Malignant Glioma Patients
Three cohorts will accrue and will be assessed independently. Each cohort will evaluate a
separate malignant glioma subpopulation. Cohort A will assess recurrent glioblastoma
multiforme (GBM) subjects who have not previously failed either bevacizumab, irinotecan or
carboplatin. Cohort B will assess recurrent grade 3 malignant glioma subjects who have not
previously failed either bevacizumab, irinotecan or carboplatin. Cohort C will assess
recurrent GBM subjects who have failed prior bevacizumab therapy but who have not failed
prior irinotecan or carboplatin. The primary endpoint of each cohort will be 6-month
progression-free survival. This study will be conducted at The Preston Robert Tisch Brain
Tumor Center at Duke.
For each cohort, bevacizumab will be administered at 10 mg/kg with irinotecan every other
week. The dose of irinotecan will be 125 mg/m2 for subjects not on Cytochrome P450, family
3, subfamily A (CYP3A)-inducing anti-epileptics (EIAEDs) and 340 mg/m2 for subjects on
EIAEDs. All subjects will also receive carboplatin on day 1 of each 28-day treatment cycle.
Carboplatin will be dosed to achieve an area under the curve (AUC) of 4.
Within 2 weeks of starting the study, subject's medical history and current medical
conditions will be recorded. A physical examination including vital signs (temperature,
respiratory rate, blood pressure, and pulse), height and weight, and neurological
examination will be done. Subject will be asked about his or her ability to perform
everyday tasks. Blood tests for assessment of a complete blood count including monitoring
liver and kidney function and a urine test to check kidney function will be performed. For
women of childbearing potential, a blood test to rule out pregnancy will be done prior to
the start of treatment. Blood tests will also check for a specific gene, which may affect
how much irinotecan subject is given. A magnetic resonance imaging (MRI) of will be
performed within 2 weeks before starting study drugs as well as after every eight weeks to
determine response and progression.
In total, approximately 3 teaspoons (15 mL) of blood will be drawn for the evaluations
before starting study drug. These tests will be repeated every 8 weeks (blood chemistries),
except a complete blood count (approximately 1 teaspoon), which will need to be repeated
every week as well as when it is deemed clinically necessary to repeat. Every 4 weeks a
urine test will be performed to test the amount of protein in subject's urine.
Placement of a central venous line may be required. Subjects will be seen in the clinic for
a physical and neurological examination every four (4) weeks. Urine and blood laboratory
tests will also be obtained at these visits. In addition, a complete blood count (about 1
teaspoon) will be obtained every week. Blood pressure measurement will be required every 2
weeks. MRI (Magnetic Resonance Imaging) scans will be done every 8 weeks (after every 2
cycles) to determine the effectiveness of the study drugs. If the tumor remains the same
size or smaller, subject will continue to receive study drugs for 12 cycles unless there are
bad side effects or unless there is evidence that the drug is not working. If evaluations
show that there may be persistent tumor after 12 cycles, subject may continue treatment.
Study drugs will stop if the subject's tumor gets larger.
Additional tests may be done at the discretion of the doctor as part of regular care
throughout the study. These exams and tests will be done to monitor the effects of the study
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
6 month progression-free survival
Annick Desjardins, MD, FRCPC
United States: Food and Drug Administration
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