This randomized phase III trial studies temozolomide (TMZ) and radiation therapy (RT) to compare how well they work with or without bevacizumab in treating patients with newly diagnosed glioblastoma or gliosarcoma. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Radiation therapy uses high-energy x-rays to kill tumor cells. Monoclonal antibodies, such as bevacizumab, may find tumor cells and help kill them. It is not yet known whether temozolomide and radiation therapy are more effective when given together with or without bevacizumab in treating glioblastoma or gliosarcoma.
PRIMARY OBJECTIVES: I. To determine whether the addition of bevacizumab to temozolomide and radiation improves efficacy as measured by progression-free and/or overall survival. II. To assess the association between overall survival and K\^trans change from T1 to T2. (ACRIN 6686) III. To assess the association between overall survival and spin echo cerebral blood volume (CBV) change from T1 to T2. (ACRIN 6686) SECONDARY OBJECTIVES: I. To determine whether the tumor molecular profile conferring a mesenchymal/angiogenic phenotype is associated with a selective increase in benefit, as measured by either overall survival or progression-free survival, from the addition of bevacizumab. II. To compare and record the toxicities of the conventional and bevacizumab-containing regimens. III. To assess the association between progression-free survival and K\^trans change from T1 to T2. (ACRIN 6686) IV. To assess the association between progression-free survival and spin echo CBV change from T1 to T2. (ACRIN 6686) V. To assess the association between values of K\^trans and spin echo CBV measured separately at T0 and at T1, and overall and progression-free survival. (ACRIN 6686) VI. To assess the association between overall survival and K\^trans changes from T0 to T1 and from T2 to T3. (ACRIN 6686) VII. To assess the association between overall survival and spin echo CBV changes from T0 to T1 and from T2 to T3. (ACRIN 6686) VIII. To assess the association between overall survival and apparent diffusion coefficient (ADC) change from T0 to T1. (ACRIN 6686) IX. To assess the association between overall survival and ADC change from T1 to T2. (ACRIN 6686) X. To assess the association between progression-free survival and ADC change from T0 to T1. (ACRIN 6686) XI. To assess the association between progression-free survival and ADC change from T1 to T2. (ACRIN 6686) XII. To assess the association between T1 values of ADC and overall and progression-free survival. (ACRIN 6686) XIII. To assess the association between change in lesion size between T1 and T3, as measured by advanced magnetic resonance imaging (MRI), and overall and progression-free survival. (ACRIN 6686) TERTIARY OBJECTIVES: I. To determine the differential acute effects associated with the addition of bevacizumab to temozolomide and radiation, as compared to the conventional arm, on measures of neurocognitive function, health-related quality of life, and symptoms during radiation and across the longitudinal progression-free interval. II. To determine the relationship of neurocognitive function, health-related quality of life, and symptoms, with progression-free and overall survival. III. To determine the association between tumor molecular profile (i.e., mesenchymal/angiogenic phenotype and proneural phenotype) and neurocognitive function, health-related quality of life, and symptoms. IV. To describe the association between health-related quality of life as measured by the European Organization for Research and Treatment Quality of Life Questionnaire-Core 30/Brain Cancer Module-20 (EORTC-QL30/BCM20) and mean symptom severity as measured by the M. D. Anderson Symptom Inventory Brain Tumor Module (MDASI-BT) in patients enrolled in this study. V. To evaluate the relationship between self-reported neurocognitive function and objectively measured tests of neurocognitive function (NCF). VI. To assess the association between measures of change in enhancing tumor size at week 22 and overall survival in participants with glioma receiving chemoradiotherapy with and without bevacizumab. VII. To assess the association between measures of change in T2-based tumor size at week 22 and overall survival in participants with glioma receiving chemoradiotherapy with and without bevacizumab. VIII. To assess the association between changes in ADC values and overall survival in participants with glioma receiving chemoradiotherapy with and without bevacizumab. OUTLINE: Patients are randomized to 1 of 2 treatment arms (there are also two registration steps prior to randomization which are labeled as "arms" in ClinicalTrials.gov to facilitate entry of results into the website). ARM I: Patients undergo intensity-modulated radiation therapy or 3-dimensional conformal radiation therapy 5 days a week for 6 weeks and receive temozolomide orally (PO) once daily (QD) for up to 7 weeks. Beginning 4 weeks after completion of chemotherapy and radiation therapy, patients receive temozolomide PO QD on days 1-5. Treatment with temozolomide repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Patients also receive placebo IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemotherapy and radiation therapy and continuing until the completion of temozolomide. ARM II: Patients undergo radiation therapy and receive temozolomide as in Arm I. Patients also receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning in week 4 of chemoradiotherapy and continuing until the completion of adjuvant temozolomide. After completion of study treatment, patients are followed up every 3 months for 1 year, every 4 months for 1 year, and then every 6 months thereafter.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
637
Undergo 3-dimentional conformal radiation therapy
Given IV
Undergo intensity-modulated radiation therapy
Correlative studies
Given IV
Ancillary studies
Given orally
Providence Hospital
Mobile, Alabama, United States
Providence Alaska Medical Center
Anchorage, Alaska, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, United States
Arizona Oncology Services Foundation
Scottsdale, Arizona, United States
Arizona Oncology Associates-West Orange Grove
Tucson, Arizona, United States
Overall Survival (OS)
Survival time was defined as time from randomization to date of death from any cause and was estimated by the Kaplan-Meier method. Patients last known to be alive were censored at the date of last contact. This analysis was planned to occur when 390 deaths had been reported.
Time frame: From randomization to date of death or last follow-up. Analysis occurs after all 390 deaths have been reported.
Progression-free Survival (PFS)
Progression-free survival was defined as time from randomization to date of progression, death, or last follow-up, and was estimated by the Kaplan-Meier method. Patients last known to be alive were censored at the date of last contact. This analysis was planned to occur when 390 deaths had been reported.
Time frame: From randomization to date of progression, death, or last follow-up for progression-free survival. Analysis occurs after all 390 deaths have been reported.
Incidence of Grade 3 and Higher Treatment-related Toxicity as Assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (AEs) Version 3.0
AEs are graded by using CTCAE 3.0. The difference between the two randomized arms in the percentage of patients with grade 3 or higher toxicities reported as possibly/probably/definitely related to protocol treatment will be tested using a chi square test.
Time frame: Up to 30 days
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