Avastin/Temozolomide/Irinotecan for Unresectable/Multifocal Glioblastoma Multiforme Multiforme

The primary objective of the study is to determine the efficacy of Avastin in combination
with temozolomide and irinotecan in terms of response rate and progression-free survival.
The secondary objectives are to describe the overall and progression-free survivals of
unresectable patients treated with upfront Avastin, temozolomide and irinotecan and to
assess the safety of Avastin, temozolomide and irinotecan in unresectable glioblastoma
patients.

This is a phase II study with the combination of Avastin, temozolomide and irinotecan for
unresectable or multifocal WHO grade IV malignant glioma patients. Patients will receive up
to four cycles of Avastin, temozolomide and irinotecan. Approximately 41 subjects will take
part in this study at Duke.

In initial Phase I and II clinical trials, 4 potential Avastin-associated safety signals
were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage.
Temozolomide's most common toxicity has been mild myelosuppression. Other, less likely,
potential toxicities include nausea and vomiting, constipation, headache, alopecia, rash,
burning sensation of skin, esophagitis, pain, diarrhea, lethargy, and hepatotoxicity. The
two major toxicities for irinotecan are myelosuppression and diarrhea.