| General information |
| Database: | DB00626 |
| Objective: | To determine the safety of the addition of bevacizumab to standard radiation therapy and daily temozolomide for newly diagnosed glioblastoma multiforme (GBM). |
| Authors: | Vredenburgh JJ, et al |
| Title: | Addition of bevacizumab to standard radiation therapy and daily temozolomide is associated with minimal toxicity in newly diagnosed glioblastoma multiforme. |
| Journal: | Int J Radiat Oncol Biol Phys. |
| Year: | 2012 |
| PMID: | 21036490 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | bevacizumab
|
| Target: | Vascular endothelial growth factor
|
| Cancer Type: | Tumors of the nervous system |
| Cancer Subtype: | malignant glioma, glioblastoma multiforme, or gliosarcoma |
| Therapy Type: | com |
| Therapeutic Combination Type: | 3 |
| Therapeutic Combination Content: | Addition of bevacizumab to standard radiation therapy and daily temozolomide |
| Study Type: | Phase II trial |
| Key Patients Feature: | All patients had newly diagnosed, histologically documented GradeIV malignant glioma, GBM, or gliosarcoma. In addition, the patientswere $18 years of age, and there was an interval of at least 2 weeks, but not >6 weeks, between the last major surgical procedure and studyenrollment. The patients could not have received any prior radiationtherapy or chemotherapy for a brain tumor; and their Karnofsky performance status had to be $60%. The hematologic parameters included a hemoglobin $9 g/dl, an ANC $1, 500 cells/ml, andplatelets $125, 000/ml. The requirements for the serum chemistries included a creatinine #1.5 mg/dl, and serum SGOT and bilirubin #1.5times the upper limit of normal. The patients could not have hada greater than Grade 1 central nervous system (CNS) hemorrhage ontheir baseline magnetic resonance imaging (MRI) or computed tomography (CT) scan. The protocol was approved by the Duke UniversityMedical Center Institutional Review Board, and all patients gave written informed consent. |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | All patients underwent a craniotomy and were at least 2 weeks postoperative. Radiation therapy was administered in 1.8Gy fractions, with the clinical target volume for the primary course treated to a dose of 45 to 50.4 Gy, followed by a boost of 9 to 14.4 Gy, to a total dose of 59.4 Gy. Patients received temozolomide at 75 mg/m(2) daily throughout the course of radiation therapy. Bevacizumab was given at 10 mg/kg intravenously every 14 days, beginning a minimum of 4 weeks postoperatively. |
| Primary End Point: | the proportion of patients alive 16 months |
| Secondary End Point: | NA |
| Patients Number: | 125 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 13.8months. The 6month PFS was 87.2%, and the 1year PFS was 63.1% |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Five patients had to stop the protocol therapy, 2 patients with pulmonary emboli, and 1 patient each with a Grade 2 central nervous system hemorrhage, Grade 4 pancytopenia, and wound dehiscence requiring surgical intervention. All 5 patients ultimately finished the radiation therapy. |
| Conclusions: | The addition of bevacizumab to standard radiation therapy and daily temozolomide was found to be associated with minimal toxicity in patients newly diagnosed with GBM. |