A Phase II Trial of Bevacizumab and Irinotecan for Patients With Recurrent High-Grade Gliomas Immediately Following Tumor Progression After Treatment w/Bevacizumab Alone: A Companion Trial to NCI Study 06-C-0064 (NCT00271609)(Bevacizumab Alone for Recurrent Gliomas)
- Bevacizumab is a humanized IgG1 monoclonal antibody (MAb) that binds all biologically
active isoforms of human vascular endothelial growth factor (VEGF, or VEGF-A) with high
affinity (kd = 1.1 nM ). The antibody consists of a human IgG1 framework and the
antigen-binding complementarity-determining regions from the murine anti-VEGF MAb
- Irinotecan is a semisynthetic derivative of camptothecin that possesses greater aqueous
solubility, greater in vitro and in vivo activity, and is associated with less severe
and more predictable toxicity than camptothecin.
- We now propose treating patients whose tumors progress on our bevacizumab alone
protocol with the combination of bevacizumab with irinotecan. We believe that this
trial design has significant power to detect a true synergistic effect between the two
agents given that the single agent activity of irinotecan is so low in patients with
recurrent malignant gliomas (2-5% response rate) and the patients being treated on this
trial will have tumors that have already progressed through bevacizumab.
- To establish data and safety regarding the anti-tumor activity of bevacizumab plus
irinotecan in patients with recurrent high-grade gliomas that have progressed on
bevacizumab alone as determined by objective radiographic response rate.
- To determine the 6 month progression-free survival of treated patients and to
characterize the pattern of changes in the number of endothelial progenitor cells over
time and across patients.
- To obtain preliminary data regarding how response to treatment (stable disease or
radiographic response) effects monthly measurements of quality of life while on study.
- Patients must have been treated on the National Cancer Institute (NCI) trial 06-C-0064;
bevacizumab alone for recurrent gliomas and now have evidence for tumor progression by
magnetic resonance imaging (MRI) scan.
- Patients with histologically proven intracranial malignant glioma.
-Patients will be treated with bevacizumab by intravenous injection at a dose of 10mg/kg and
irinotecan at a dose of 125 mg/m^2 for patients on non-enzyme-inducing anti-epileptic drugs
(NEIAED) and 340 mg/m^2 for patients on enzyme-inducing anti-epileptic drugs (EIAED) every
two weeks on a 4-week cycle.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Radiographic Response Rate (Malignant Glioma Participants)
Definition of response: complete response (CR) is the complete disappearance of all measurable and evaluable disease. Partial response (PR) is greater than or equal to a 50% decrease compared to baseline in the sum of products of perpendicular diameters of all measurable lesions. Stable/No response (SD, NR)does not qualify for CR, PR, or progression. Progression is a 25% increase in the sum of products of all measurable lesions (or two target lesions if too numerous over the smallest sum observed (over baseline if no decrease) using the same techniques as baseline.
23 months (date of first enrollment to 1 month after last progression)
Howard A Fine, M.D.
National Cancer Institute, National Institutes of Health
United States: Federal Government
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