Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

Duke University

Status and phase: Completed; Phase 2

Conditions: Glioblastoma Multiforme

Treatments: Drug: Bevacizumab; Drug: Metronomic Temozolomide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00501891

AVF3821s

P04860

Pro00000404

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 32 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must have histologically confirmed diagnosis of WHO grade IV primary malignant glioma
• Karnofsy Performance Status (KPS) >/= 60%
• Evidence of measurable primary CNS neoplasm on contrast-enhanced MRI.
• An interval of at least 4 weeks between prior surgical resection or 1 week from a biopsy and enrollment on this protocol
• An interval of at least 4 weeks from the end of prior radiotherapy or one week from the end of a cycle of chemotherapy and enrollment on this protocol.
• No evidence of CNS hemorrhage on the baseline MRI or CT scans

Exclusion criteria

• Life expectancy < 8 weeks
• Pregnancy or breast feeding
• Progression to metronomic temozolomide, defined as tumor progression while taking daily temozolomide or progression within 4 weeks of stopping metronomic temozolomide
• Inadequately controlled hypertension (defined as systolic blood pressure >150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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32 participants in 1 patient group

Bevacizumab and Metronomic Temozolomide

Experimental group

Description:

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.

Treatment:

Drug: Metronomic Temozolomide

Drug: Bevacizumab