Avastin / Irinotecan in Patients With Recurrent or Progressive Malignant Glioma
Status:
Unknown status
Trial end date:
2013-03-01
Target enrollment:
Participant gender:
Summary
Malignant glioma are the most common and aggressive primary brain tumors in adults. Despite
advances in multimodal treatment including surgery, radiation and chemotherapy, most patients
have a dismal prognosis of 9-15 months (Stupp et al., NEJM 2005).
A major reason for the aggressiveness of malignant glioma is a pronounced tumor
neovascularization, mainly driven by the vascular endothelial growth factor (VEGF) and its
receptors. The therapeutic monoclonal antibody Bevacizumab (Avastin®) inhibits the VEGF
pathway by binding the VEGF ligand. In Magnetic Resonance Imaging (MRI) this treatment
reduces contrast enhancement by restoring both, the blood-brain-barrier and the destabilized
vessel integrity. Furthermore, it raises the sensitivity of co-administered chemotherapeutics
such as Irinotecan. In conclusion, anti-angiogenic therapy leads to the problem that the
routinely used MRI techniques cannot distinguish anti-vascular effects from true anti-tumor
effects.
The study hypothesis of the clinical trial part is that in 35% of malignant glioma patients
Avastin / Irinotecan chemotherapy results in objective tumor responses assessed by standard /
functional MRI and FET- /FLT-PET neuroimaging. The study hypothesis for the translational
study part is that the expression of the molecular targets of Avastin and Irinotecan in
malignant glioma tissue ( = tumor and vascular cells) are predictive for Avastin / Irinotecan
therapy induced treatment response measured by functional MRI and FET- / FLT-PET imaging.