Avastin in Combination With Radiation (XRT) & Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma (GBM) and Gliosarcomas
Primary objective: To use overall survival to assess the efficacy of the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan in the treatment of grade IV malignant glioma patients following surgical resection.
Secondary objective: To determine the progression-free survival following the combination of radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.
Exploratory Objective: To explore the relationship between biomarkers and outcome (overall survival and progression-free survival) among patients with grade IV malignant glioma treated with radiation therapy, temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.
To describe the toxicity of radiation therapy,temozolomide and Avastin followed by Avastin, temozolomide, and irinotecan.
Radiation: Radiation Therapy (XRT)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Avastin in Combination With Radiation and Temozolomide, Followed by Avastin, Temozolomide and Irinotecan for Glioblastoma Multiformes and Gliosarcomas|
- 16-month Overall Survival (OS) [ Time Frame: 16 months ] [ Designated as safety issue: No ]Percentage of participants surviving sixteen months from the start of study treatment. OS was defined as the time from the date of study treatment initiation to the date of death due to any cause.
- 12-month Progression-free Survival (PFS) [ Time Frame: 12 months ] [ Designated as safety issue: No ]Percentage of participants surviving twelve months from the start of study treatment without progression of disease. PFS was defined as the time from the date of study treatment initiation to the date of the first documented progression according to the Macdonald criteria, or to death due to any cause.
- Number of Patients Experiencing a Central Nervous System (CNS) Hemorrhage or a Systemic Hemorrhage [ Time Frame: 55 months ] [ Designated as safety issue: Yes ]Number of times a CNS hemorrhage or systemic hemorrhage was experienced
- Number of Patients Experiencing a Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity [ Time Frame: 55 months ] [ Designated as safety issue: Yes ]Number of times a grade ≥ 4 hematologic or grade ≥ 3 non-hematologic toxicity was experienced
|Study Start Date:||July 2007|
|Study Completion Date:||May 2013|
|Primary Completion Date:||August 2011 (Final data collection date for primary outcome measure)|
|Experimental: Avastin, radiation, temozolomide, and irinotecan||
Avastin will be administered 10 mg/kg every other week beginning a minimum of 28 days after last major surgical procedure, open biopsy, or significant traumatic injury. Following completion of XRT, patients will receive treatment that includes 6 cycles of Avastin, beginning a minimum of 14 days after last XRT.
Other Name: BevacizumabDrug: Temozolomide
Daily temozolomide 75 mg/m2/day for 6.5 weeks of radiation treatment. Following completion of XRT, patients will receive treatment including temozolomide 200 mg/m2/day on the 1st 5 days of each 28-day cycle.
Other Name: TemodarRadiation: Radiation Therapy (XRT)
Treatment with standard XRT (radiation) for 6.5 weeks.Drug: Irinotecan
Following completion of XRT, patients will receive 6 cycles of treatment that includes irinotecan. Beginning a minimum of 14 days after last XRT, the irinotecan dose will depend on whether the patient is on enzyme-inducing antiepileptic drugs (EIAED). (EIAED:340 mg/m2 every other week, non-EIAED: 125 mg/m2.)
The standard of care for grade IV gliomas is radiation therapy with daily temozolomide, followed by 6 months of temozolomide. The majority of patients progress and die of their tumor. Many glioma patients are resistant to temozolomide because the tumors have high O(6)-methylguanine-DNA methyltransferase (MGMT), conferring resistance. Irinotecan is synergistic with temozolomide, and the combination may overcome high MGMT. Vascular endothelial growth factor (VEGF) is present on the cell surface and around malignant gliomas. It appears that the presence of vascular endothelial growth factor is a prognostic growth factor with more VEGF expression correlating with a poor prognosis. Monoclonal antibodies to VEGF have inhibited growth of malignant gliomas in a mouse xenograft. Avastin is a humanized monoclonal immunoglobulin G (IGG) 1 antibody that binds to and inhibits the biologic activity of human vascular endothelial growth factor. The combination of Avastin and irinotecan was safe and demonstrated high activity against recurrent malignant gliomas. The combination of Avastin, temozolomide, and irinotecan as the initial therapy may maximize the chance for long-term survival. There are other studies completed or ongoing for newly diagnosed glioblastoma (GBM) patients, including a Radiation Therapy Oncology Group (RTOG) study that added irinotecan to temozolomide following standard radiation therapy and temozolomide, and a University of California, Los Angeles (UCLA) study that added Avastin to standard radiation therapy and temozolomide followed by Avastin and temozolomide.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00597402
|United States, North Carolina|
|Duke University Health System|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Annick Desjardins, MD, FRCPC||Duke University Health System|