Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

Glioblastoma Multiforme Clinical Trial

Official title:

A Phase II Study of Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00501891
• Other study ID #: Pro00000404
• Secondary ID: AVF3821sP04860
• Status: Completed
• Phase: Phase 2
• First received: July 13, 2007
• Last updated: May 17, 2013
• Start date: July 2007
• Est. completion date: November 2009

Study information

• Verified date: March 2013
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: November 2009
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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)

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glioblastoma
• Glioblastoma Multiforme

Intervention

Drug:
• Bevacizumab
Bevacizumab administered intravenously 10mg/kg every other week.
• Metronomic Temozolomide
Temozolomide 50mg/m2 given orally on a daily basis.

Locations

Country	Name	City	State
United States	Duke University Medical Center (Brain Tumor Center)	Durham	North Carolina

Sponsors (3)

Lead Sponsor	Collaborator
Duke University	Genentech, Inc., Schering-Plough

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	6-Month Progression-free Survival	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).]	6 months	No
Secondary	Response Rate	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.	27 months	No
Secondary	Incidence and Severity of CNS Hemorrhage and Systemic Hemorrhage	Number of participants experiencing a Central Nervous System (CNS) hemorrhage or systemic hemorrhage	27 months	Yes
Secondary	Incidence of Grade = 4 Hematologic or Grade = 3 Non-hematologic Toxicity	Number of participants experiencing a grade =4 hematologic or grade =3 non-hematologic toxicity	27 months	Yes

External Links

•   The Preston Robert Tisch Brain Tumor Center at Duke