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Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

Primary Purpose

Glioblastoma Multiforme

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Bevacizumab
Metronomic Temozolomide
Sponsored by
Duke University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Glioblastoma Multiforme focused on measuring Glioblastoma Multiforme, Brain and Central Nervous System Tumors, Recurrent Malignant Glioma, Recurrent Glioblastoma Multiforme, Avastin, Bevacizumab, Temodar, Temozolomide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • Duke University Medical Center (Brain Tumor Center)

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Bevacizumab and Metronomic Temozolomide

Arm 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.

Outcomes

Primary Outcome Measures

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).]

Secondary Outcome Measures

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.
Incidence and Severity of CNS Hemorrhage and Systemic Hemorrhage
Number of participants experiencing a Central Nervous System (CNS) hemorrhage or systemic hemorrhage
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

Full Information

First Posted
July 13, 2007
Last Updated
May 17, 2013
Sponsor
Duke University
Collaborators
Genentech, Inc., Schering-Plough
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1. Study Identification

Unique Protocol Identification Number
NCT00501891
Brief Title
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

2. Study Status

Record Verification Date
March 2013
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
November 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Genentech, Inc., Schering-Plough

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Glioblastoma Multiforme
Keywords
Glioblastoma Multiforme, Brain and Central Nervous System Tumors, Recurrent Malignant Glioma, Recurrent Glioblastoma Multiforme, Avastin, Bevacizumab, Temodar, Temozolomide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Bevacizumab and Metronomic Temozolomide
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Other Intervention Name(s)
Avastin
Intervention Description
Bevacizumab administered intravenously 10mg/kg every other week.
Intervention Type
Drug
Intervention Name(s)
Metronomic Temozolomide
Other Intervention Name(s)
Temodar
Intervention Description
Temozolomide 50mg/m2 given orally on a daily basis.
Primary Outcome Measure Information:
Title
6-Month Progression-free Survival
Description
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).]
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Response Rate
Description
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.
Time Frame
27 months
Title
Incidence and Severity of CNS Hemorrhage and Systemic Hemorrhage
Description
Number of participants experiencing a Central Nervous System (CNS) hemorrhage or systemic hemorrhage
Time Frame
27 months
Title
Incidence of Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity
Description
Number of participants experiencing a grade ≥4 hematologic or grade ≥3 non-hematologic toxicity
Time Frame
27 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Annick Desjardins, MD
Organizational Affiliation
Duke Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center (Brain Tumor Center)
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21792866
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.
Results Reference
result
Links:
URL
http://cancer.duke.edu/btc/
Description
The Preston Robert Tisch Brain Tumor Center at Duke

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Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

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