Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma
This is a phase II study of the combination of Avastin and metronomic temozolomide in recurrent malignant glioma patients. The primary objective will be to determine the efficacy of Avastin (bevacizumab) and metronomic temozolomide in malignant glioma patients. The secondary objective will be to determine the safety of Avastin, 10 mg/kg every other week, in combination with metronomic temozolomide in terms of progression-free survival.
Drug: Metronomic Temozolomide
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma|
- 6-Month Progression-free Survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]Percentage of participants surviving six 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. [Optional: Macdonald criteria are standard criteria in neuro-oncology. Tumor assessment was made according to the adapted MacDonald criteria based on the combined evaluation of: 1) assessment of the MRI scan for measurable, evaluable, and new lesions (made by the independent external expert too), 2) overall assessment of neurological performance (made by the investigator), 3) concomitant steroid use (as reported by the investigator).]
- Response Rate [ Time Frame: 27 months ] [ Designated as safety issue: No ]The number of participants with complete or partial response as determined by a modification of the Macdonald criteria. Complete response was defined as complete disappearance on MR/CT of all enhancing tumor and mass effect, off all corticosteroids (or receiving only adrenal replacement doses), accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks. Partial Response was defined as greater than or equal to 50% reduction in tumor size on MR/CT by bi-dimensional measurement, on a stable or decreasing dose of corticosteroids, accompanied by a stable or improving neurologic examination, and maintained for at least 4 weeks.
- Incidence and Severity of CNS Hemorrhage and Systemic Hemorrhage [ Time Frame: 27 months ] [ Designated as safety issue: Yes ]Number of participants experiencing a Central Nervous System (CNS) hemorrhage or systemic hemorrhage
- Incidence of Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity [ Time Frame: 27 months ] [ Designated as safety issue: Yes ]Number of participants experiencing a grade ≥4 hematologic or grade ≥3 non-hematologic toxicity
|Study Start Date:||July 2007|
|Study Completion Date:||November 2009|
|Primary Completion Date:||December 2007 (Final data collection date for primary outcome measure)|
Experimental: Bevacizumab and Metronomic Temozolomide
Patients will receive up to 12 cycles of bevacizumab (Avastin) and metronomic temozolomide (Temodar), and each cycle is 28 days. Bevacizumab will be administered at 10 mg/kg every other week beginning a minimum of 7 days after a biopsy or 28 days after a craniotomy. Temozolomide will be dosed at 50 mg/m2 daily in a 28-day cycle.
Bevacizumab administered intravenously 10mg/kg every other week.
Other Name: AvastinDrug: Metronomic Temozolomide
Temozolomide 50mg/m2 given orally on a daily basis.
Other Name: Temodar
This is a phase II trial of the combination of Avastin and metronomic temozolomide in recurrent WHO grade IV malignant glioma patients. Patients will receive up to 12 cycles of Avastin and temozolomide and cycles are continuous 28 days. Patients will receive daily temozolomide at a dose of 50mg/m2 and will receive Avastin every other week at a dose of 10mg/kg. Patients will be required to have a baseline MRI within 2 weeks of starting treatment and a repeat MRI every 8 weeks. A total of 32 patients will be enrolled at Duke.
Patients with recurrent malignant gliomas have a very poor prognosis, so new therapies are needed. Given the activity of metronomic temozolomide and the safety and activity of Avastin against malignant glioma, it is reasonable to study the combination in recurrent malignant glioma patients.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00501891
|United States, North Carolina|
|Duke University Medical Center (Brain Tumor Center)|
|Durham, North Carolina, United States, 27710|
|Principal Investigator:||Annick Desjardins, MD||Duke University Health System|