The primary objective of this study is to use 6-month progression-free survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan in the treatment of grade IV malignant glioma patients following surgical resection. Secondary objectives are to determine the overall survival following the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan and to describe the toxicity of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan.~The study will have survival and toxicity endpoints. Patients will be treated with standard radiation therapy and daily temozolomide for 6 and a half weeks of radiation. Avastin will be administered every other week beginning a minimum of 28 days after the last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of radiation therapy, patients will have a MRI and if there is no evidence of disease progression, patients will receive 12 cycles of Avastin, temozolomide, and topotecan (beginning a minimum of 14 days after the last radiation treatment). Subjects will be identified by the investigator as those patients who have newly diagnosed grade 4 malignant glioma (glioblastoma multiforme or gliosarcoma), and be within 6 weeks of the last major surgical procedure, craniotomy, open biopsy, or stereotactic biopsy.~Fifty (50) patients will initially be accrued to the study and the overall efficacy of the treatment regimen assessed. Analyses will be conducted within subgroups defined by methylation status.~Early side effects of radiation that may start during radiation include hair loss, scalp redness, inflammation of the ear canals, and fatigue. There is a small chance of long-term effects from radiation, occurring after months or years after completion. These may include worsening of mental function, hearing, vision, strength and coordination. In initial Phase I and II clinical trials, four potential Avastin-associated safety signals were identified: hypertension, proteinuria, thromboembolic events, and hemorrhage. Temozolomide has been well tolerated by both adults and children with the most common toxicity being 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. With topotecan, reversible myelosuppression with leukopenia and thrombocytopenia is dose limiting. Nausea and vomiting, as well as diarrhea and alopecia, are frequent. Moderate fatigue, transient elevation of hepatic transaminase levels, stomatitis, anemia, fever, mucositis, flu-like symptoms, and rash have been reported.
This is a phase II study of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and topotecan in grade IV malignant glioma patients.