Bevacizumab in Combination With Metronomic Temozolomide for Recurrent Malignant Glioma

May 17, 2013 updated by: Duke University

A Phase II Study of 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center (Brain Tumor Center)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.
Drug: Bevacizumab
Bevacizumab administered intravenously 10mg/kg every other week.
Other Names:
  • Avastin
Drug: Metronomic Temozolomide
Temozolomide 50mg/m2 given orally on a daily basis.
Other Names:
  • Temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
6-Month Progression-free Survival
Time Frame: 6 months
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response Rate
Time Frame: 27 months
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
Incidence and Severity of CNS Hemorrhage and Systemic Hemorrhage
Time Frame: 27 months
Number of participants experiencing a Central Nervous System (CNS) hemorrhage or systemic hemorrhage
27 months
Incidence of Grade ≥ 4 Hematologic or Grade ≥ 3 Non-hematologic Toxicity
Time Frame: 27 months
Number of participants experiencing a grade ≥4 hematologic or grade ≥3 non-hematologic toxicity
27 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Duke University

Collaborators

Genentech, Inc.
Schering-Plough

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Actual)

December 1, 2007

Study Completion (Actual)

November 1, 2009

Study Registration Dates

First Submitted

July 13, 2007

First Submitted That Met QC Criteria

July 13, 2007

First Posted (Estimate)

July 16, 2007

Study Record Updates

Last Update Posted (Estimate)

May 27, 2013

Last Update Submitted That Met QC Criteria

May 17, 2013

Last Verified

March 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00000404
  • AVF3821s
  • P04860

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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