| General information |
| Database: | DB00623 |
| Objective: | Despite treatment with the current standardofcare therapies, patients with newly diagnosed glioblastoma multiforme (GBM) exhibit dismal prognoses. Bevacizumab has demonstrated activity in patients with recurrent GBM andphase 2 trials indicate that the combination of bevacizumab with standardofcare therapy is feasible and active for patients with newly diagnosed GBM. |
| Authors: | Chinot OL, et al |
| Title: | AVAglio:phase 3 trial of bevacizumab plus temozolomide and radiotherapy in newly diagnosed glioblastoma multiforme. |
| Journal: | Adv Ther. |
| Year: | 2011 |
| PMID: | 21432029 |
| Trial Design |
| Clinical Trial Id: | protocal |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | glioblastoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | bevacizumab plus temozolomide and radiotherapy |
| Study Type: | Phase III Trial |
| Key Patients Feature: | Adult patients (more than and equal to 18 years of age) with newlydiagnosed supratentorial GBM histologicallyconfirmed from surgical resection or biopsytissue are eligible for enrolment into AVAglio.Study treatment has to be initiated >28 and<49 days following the last surgical procedureand a tumor tissue block has to be available forpathology central review and analysis of MGMTstatus. World Health Organization (WHO)performance status has to be less than and equal to 2. Corticosteroiddose has to be stable or decreasing within 5 daysprior to randomization. Hematologic, hepatic, and renal function need to be adequate andblood coagulation parameters acceptable. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | placebo plus temozolomide and radiotherapy |
| Treatment Info: | Eligible patients are randomized (1:1) to thetreatment arms (bevacizumab or placebo) underdoubleblind conditions after central stratificationfor recursive partitioning analysis class as definedby EORTC/NCIC (3, 4, and 5) and region. Allpatients receive local irradiation (60 Gy total dosein 2 Gy fractions 5 days per week for 6 weeks)and temozolomide (75 mg/m2 orally from thefirst day to the last day of radiotherapy for amaximum of 49 days) during the concurrentphase, followed by a 4week break fromtemozolomide therapy starting the day after the last dose of radiotherapy, and thenadjuvant temozolomide (150200 mg/m2 dailyon days 15 of six 4week cycles) during themaintenancephase. |
| Primary End Point: | superior OS and PFS (investigator assessment) |
| Secondary End Point: | 1year and 2year survival rates, PFS, safety, and healthrelated quality of life |
| Patients Number: | NA |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | the6month progression free survival (PFS) rate (43%and 50%), objective response rate (ORR; 28%and 38%), and median overall survival (OS; 9.2and 8.7 months) were compelling |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | median PFS (12 vs. 7 months, P=0.0001) |
| Median OS A vs. C: | median OS (24.0 vs. 17.5 months, P=0.09) were higher in the cohort receiving bevacizumab concurrently with standard therapy. |
| Adverse Event(agent arm): | toxicity of the combination was acceptable in the aforementioned studies. |
| Conclusions: | NA |