Bi-weekly Temozolomide Plus Bevacizumab for Adult Patients With Recurrent Glioblastoma Multiforme

March 28, 2017 updated by: Michael Badruddoja, MD, Center for Neurosciences, Tucson

Phase II Study of Bi-Weekly Temozolomide Plus Bevacizumab for Adult Patients With Recurrent Glioblastoma Multiforme

Primary objective - to determine the 6-month progression free survival (PFS) of adult patients with recurrent glioblastoma multiforme/gliosarcoma treated with bi-weekly temozolomide plus (Avastin) bevacizumab.

Secondary objectives - to determine radiographic response including specialized MRI sequences, safety and overall survival of adult patients with with recurrent glioblastoma multiforme/gliosarcoma treated with bi-weekly temozolomide plus bevacizumab (Avastin). Additionally, tumor DNA (MGMT) analysis as it relates to survival will be evaluated.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a phase II study of the combination of Avastin and temozolomide for patients with recurrent glioblastoma multiforme. Avastin is administered intravenously at a dose of 10 mg/kg on days 1 and 15 every 28 days and temozolomide is administered at a dose of 100 mg/m2 on days 1-5 and 15-19 every 28 days (one cycle). Patients will have a baseline MRI, an MRI scan after the first cycle and every other cycle after that. If there is no evidence of disease progression or unacceptable toxicity, patients will receive one year of therapy. If there is evidence of added benefit (eg: tumor regression), patients can stay on treatment longer than one year, per investigator discretion.

Study Type

Interventional

Enrollment (Actual)

30

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
    • Arizona
      • Tucson, Arizona, United States, 85718
        • Center for Neurosciences

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 to 83 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients must have histologically confirmed diagnosis of a glioblastoma multiforme/gliosarcoma and:

  • Must have completed at least 2 cycles of adjuvant chemotherapy
  • Age > 18 years
  • Karnofsky > 60%
  • Hematocrit > 29%, ANC > 1,500 cells/dl, platelets > 125,000 cells/dl
  • Serum creatinine < 1.5 mg/dl, BUN < 25 mg/dl, serum SGOT and bilirubin < 1.5 times upper limit of normal
  • If on corticosteroids, must be on a stable dose for 1 week prior to entry; if clinically possible, the dose should not be escalated over entry dose level
  • Signed informed consent approved by the Institutional Review Board prior to study entry
  • If sexually active, will take contraceptive measures for the duration of the treatments

Exclusion Criteria:

  • Prior toxicity grade ≥ 3 with TMZ
  • Prior treatment with bevacizumab
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control
  • Concurrent severe and/or uncontrolled medical disease that could compromise participation in the study
  • Acute or chronic liver disease (i.e., hepatitis, cirrhosis)
  • Confirmed diagnosis of HIV infection
  • Have received investigational drugs less than 4 weeks prior to entry on this study or who have not recovered from the toxic effects of such therapy
  • Have received chemotherapy within 2 weeks prior (6 weeks for nitrosourea) to entry on this study, or who have not recovered from the toxic effects of such therapy
  • Have received biologic, immunotherapeutic or cytostatic agents within 1 week prior to entry on this study or who have not recovered from the toxic effects of such therapy
  • Less than 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant
  • Have received radiation therapy within 2 weeks prior to entry on this study or who have not recovered from the toxic effects of such therapy.
  • Surgical resection of brain tumor within 4 weeks prior to entry on this study or who have not recovered from side effects of such therapy
  • Have had any surgery other than resection of a brain tumor within 4 weeks prior to entry on this study or who have not recovered from side effects of such therapy
  • Unwilling to or unable to comply with the protocol
  • Evidence of tumor progression within on immediate post radiation brain imaging
  • Have not received at least 2 cycles of adjuvant chemotherapy
  • Life expectancy of less than 12 weeks
  • Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study

Bevacizumab-Specific Exclusions:

  • Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • New York Heart Association (NYHA) Grade II or greater congestive heart failure (see Appendix E)
  • History of myocardial infarction or unstable angina within 6 months
  • History of stroke or transient ischemic attack within 6 months
  • Significant vascular disease (e.g., aortic aneurysm, requiring surgical repair or recent peripheral arterial thrombosis) within 6 months
  • Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 1 or anticipation of need for major surgical procedure during the course of the study
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days
  • History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
  • Serious, non-healing wound, active ulcer, or untreated bone fracture.
  • Proteinuria as demonstrated by a UPC ratio greater than or equal to 1.0 at screening
  • Known hypersensitivity to any component of bevacizumab

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Open Label
temozolomide plus bevacizumab administered as open label single arm treatment
Drug: temozolomide and bevacizumab
oral temozolomide 100 mg/m2 days 1-5 & 15-19 every 28-day cycle plus intravenous bevacizumab 10 mg/kg days 1 & 5 every 28-day cycle
Other Names:
  • Avastin
  • Temodar

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
6-month progression-free survival.
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Radiographic response (Gd-MRI) including specialized MRI sequences (T2/FLAIR).
Time Frame: every eight weeks
every eight weeks
Incidence and severity of toxicity.
Time Frame: 6 months
6 months
Tumor DNA (MGMT) analysis as it relates to survival.
Time Frame: 6 months
6 months

Collaborators and Investigators

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

Sponsor

Center for Neurosciences, Tucson

Collaborators

Genentech, Inc.

Investigators

  • Principal Investigator: Michael A. Badurddoja, MD, Center for Neurosciences

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

April 1, 2009

Primary Completion (ACTUAL)

December 1, 2014

Study Completion (ACTUAL)

December 1, 2014

Study Registration Dates

First Submitted

April 16, 2009

First Submitted That Met QC Criteria

April 16, 2009

First Posted (ESTIMATE)

April 17, 2009

Study Record Updates

Last Update Posted (ACTUAL)

March 30, 2017

Last Update Submitted That Met QC Criteria

March 28, 2017

Last Verified

March 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AVF4514s

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

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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