Clinical trial NCT00501891: Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma
Official title: A Phase II Study of Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Glioblastoma Multiforme
Keywords: Glioblastoma Multiforme
Brain and Central Nervous System Tumors
Recurrent Malignant Glioma
Recurrent Glioblastoma Multiforme
Avastin
Bevacizumab
Temodar
Temozolomide
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Genentech, Inc.
name: Schering-Plough
First posted: 2007-07-16
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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)

Primary outcomes:
measure: 6-Month Progression-free Survival
timeFrame: 6 months
Secondary outcomes:
measure: Response Rate
timeFrame: 27 months
measure: Incidence and Severity of CNS Hemorrhage and Systemic Hemorrhage
timeFrame: 27 months
measure: Incidence of Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity
timeFrame: 27 months
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center (Brain Tumor Center)
state: North Carolina
Study officials:
affiliation: Duke Health
name: Annick Desjardins, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Desjardins A, Reardon DA, Coan A, Marcello J, Herndon JE 2nd, Bailey L, Peters KB, Friedman HS, Vredenburgh JJ. Bevacizumab and daily temozolomide for recurrent glioblastoma. Cancer. 2012 Mar 1;118(5):1302-12. doi: 10.1002/cncr.26381. Epub 2011 Jul 26.