Bevacizumab in Reducing CNS Side Effects in Patients Who Have Undergone Radiation Therapy to the Brain for Primary Brain Tumor, Meningioma, or Head and Neck Cancer

April 21, 2014 updated by: National Cancer Institute (NCI)

A Randomized Phase II Trial of Bevacizumab to Control Brain Radiation Damage

Bevacizumab may reduce CNS side effects caused by radiation therapy. This randomized phase II trial is studying how well bevacizumab works in reducing CNS side effects in patients who have undergone radiation therapy to the brain for primary brain tumor, meningioma, or head and neck cancer.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVE:

I. Determine to what extent bevacizumab can reduce active radiation toxicity to the CNS in patients who have undergone cranial irradiation for primary brain neoplasm, meningioma, or head and neck cancer.

SECONDARY OBJECTIVES:

I. Determine to what extent this drug can reduce dexamethasone dependence in these patients.

II. Determine to what extent this drug can improve neurologic function in these patients.

III. Determine to what extent this drug can improve quality of life of these patients.

OUTLINE: This is a randomized, placebo-controlled, crossover, double-blind study. Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.

Patients in arm II who have failed to respond to treatment at 6 or 12 weeks may cross over to arm I and receive 2 courses of bevacizumab as in arm I. Patients in arm I (including crossover patients) who have responded to treatment may receive 2 additional courses of bevacizumab.

Patients undergo MRI after courses 2 and 4.

Quality of life and neurologic function are assessed at baseline, periodically during study treatment, and at 12 and 24 weeks after completion of study treatment.

After completion of study treatment, patients are followed at 12 and 24 weeks.

Study Type

Interventional

Enrollment (Actual)

11

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
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson Cancer 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:

  • No evidence of bleeding diathesis or coagulopathy
  • Fertile patients must use effective contraception during and for >= 2 months after completion of study therapy
  • No diarrhea >= grade 1
  • Histologically confirmed primary brain neoplasm, meningioma, or head and neck cancer [WHO grade 2 or 3 disease--no WHO grade 4 primary brain neoplasms (i.e., glioblastoma or gliosarcoma)]

  • Patients with head and neck cancer must not have any of the following:

    • Evidence of metastatic disease
    • Evidence of tumor invasion to major vessels (e.g., the carotid)
    • History of bleeding related to tumor or radiotherapy during or after completion of radiotherapy
  • Must have undergone cranial irradiation
  • Must have radiographic evidence to support the diagnosis of radiation necrosis and/or surgical biopsy evidence of necrosis without tumor within the past 2 months
  • Must have evidence of progressive neurologic signs or symptoms appropriate to the location of the radiation necrosis
  • No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No significant traumatic injury within the past 28 days
  • No evidence of active CNS hemorrhage
  • Karnofsky performance status 60-100%

  • No clinically significant cardiovascular disease, including any of the following:

    • Inadequately controlled hypertension (i.e., systolic BP > 140 mm Hg and/or diastolic BP > 90 mm Hg despite antihypertensive medication)
    • Large vessel cerebrovascular accident within the past 6 months
    • Myocardial infarction or unstable angina within the past 6 months

  • No clinically significant cardiovascular disease, including any of the following:

    • NYHA class II-IV congestive heart failure
    • Serious or inadequately controlled cardiac arrhythmia
    • Significant vascular disease (e.g., aortic aneurysm or history of aortic dissection)
    • Clinically significant peripheral vascular disease
  • At least 6 months since prior radiotherapy
  • Platelet count > 75,000/mm^3
  • Granulocyte count > 1,500/mm^3
  • Creatinine < 1.0 times ULN
  • AST < 2.5 times ULN
  • Not pregnant or nursing
  • Negative pregnancy test
  • Prior chemotherapy for tumor allowed
  • Prior tyrosine kinase inhibitors of VEGF receptor (VEGFR) allowed
  • More than 28 days since prior and no concurrent major surgical procedure or open biopsy
  • Concurrent dexamethasone allowed provided patient is on a stable dose for >= 1 week prior to study entry

  • Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed provided the following criteria are met:

    • In-range INR (usually between 2 and 3) and patient is on a stable dose of oral anticoagulant for 1 week or on a stable dose of low molecular weight heparin
    • No active bleeding or pathological condition that carries a high risk of bleeding
  • Concurrent full-dose anticoagulants (e.g., warfarin) with PT INR > 1.5 allowed provided the following criteria are met: No evidence of serious or nonhealing wound, ulcer, or bone fracture
  • No concurrent chemotherapy or tyrosine kinase inhibitors of VEGFR
  • No prior bevacizumab
  • More than 7 days since prior core biopsy
  • History of seizures allowed provided the patient is receiving anticonvulsant therapy
  • Hemoglobin >= 9.0 g/dL
  • Bilirubin =< 1.5 times upper limit of normal (ULN)
  • No other concurrent investigational agents

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: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm I
Patients receive bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Procedure: quality-of-life assessment
Other Names:
  • quality of life assessment
Procedure: magnetic resonance imaging
Other Names:
  • MRI
  • NMRI
  • nuclear magnetic resonance imaging
  • NMR imaging
Drug: bevacizumab
Given IV
Other Names:
  • Avastin
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • rhuMAb VEGF
Placebo Comparator: Arm II
Patients receive placebo IV over 30-90 minutes on day 1. Treatment repeats every 3 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Procedure: quality-of-life assessment
Other Names:
  • quality of life assessment
Procedure: magnetic resonance imaging
Other Names:
  • MRI
  • NMRI
  • nuclear magnetic resonance imaging
  • NMR imaging
Drug: placebo
Given IV
Other Names:
  • PLCB

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Response ( > 25% Reduction in T2 Flair) From Baseline to Evaluation at 6 Weeks Post Treatment
Time Frame: Baseline to 12 weeks
Change in magnetic resonance imaging (MRI) from baseline to evaluation at 6 weeks for participants where MRI changes are based on the size of edema (T2 FLAIR) and Gd-contrast enhancement (lesion diameter and perfusion/dynamic). A 25% reduction in T2 flair volume constitutes a response for study.
Baseline to 12 weeks

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Monica Loghin, M.D. Anderson Cancer Center

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

June 1, 2007

Primary Completion (Actual)

August 1, 2010

Study Completion (Actual)

August 1, 2010

Study Registration Dates

First Submitted

June 25, 2007

First Submitted That Met QC Criteria

June 25, 2007

First Posted (Estimate)

June 27, 2007

Study Record Updates

Last Update Posted (Estimate)

May 9, 2014

Last Update Submitted That Met QC Criteria

April 21, 2014

Last Verified

April 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2009-00256 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • P30CA016672 (U.S. NIH Grant/Contract)
  • N01CM62202 (U.S. NIH Grant/Contract)
  • 7955 (CTEP)
  • CDR0000553135
  • 2006-0890 (Other Identifier: M D Anderson Cancer Center)

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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