Clinical Trial: Glyburide vs Placebo as Prophylaxis Against Cerebral Edema in Patients Receiving Radiosurgery for Brain Metastases (RAD 1502/UAB 1593)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Pilot Study and Phase II Double Blind Placebo Controlled Randomized Trial Examining the Safety and Efficacy of Glyburide as Prophylaxis Against Cerebral Edema in Patient

Brief Summary:

Primary Objectives:

Pilot Portion: To determine the feasibility and safety of administering oral glyburide to non-diabetic patients receiving stereotactic radiosurgery (SRS) for newly diagnosed brain metastases.

Randomized Portion: To determine the number of patients with newly diagnosed brain metastases who have an increase in edema as measured on volumetric FLAIR imaging and the number of patients that require dexamethasone administration (or any corticosteroid administration with the purpose of treating cerebral edema) from the day of SRS to one month follow-up MRI in the group receiving glyburide versus placebo.


Detailed Summary:

Many patients with cancer that has spread to the brain have side effects caused by swelling around the tumors. A common treatment for this swelling is a medicine called dexamethasone. Dexamethasone is a steroid. Long-term use of steroids has several known side effects.

Recent studies have shown that a drug commonly used in to control high blood sugar in diabetes, called glyburide, can decrease brain swelling in patients with brain damage or stroke. Animal studies have shown that this drug may also reduce swelling from tumors in the brain. Researchers are interested in whether glyburide could treat brain swelling as well as dexamethasone with fewer side effects.

This study is being done to see whether glyburide is safe to be used in patients without diabetes in combination with receiving SRS for brain metastases. This study will also find out if glyburide will decrease brain swelling in patients that get radiosurgery (SRS) for brain metastases. This study will also find out if taking glyburide will decrease the chance of needing steroids due to brain swelling that is causing symptoms. It is not yet known, but it is the investigators' hope that glyburide will both decrease brain swelling and lessen the chance of needing steroids.


Sponsor: University of Alabama at Birmingham

Current Primary Outcome:

  • Pilot Portion: Occurrence of Dose Limiting Toxicities (DLTs) [ Time Frame: 4 months ]
    Assessed between the time of glyburide initiation and the time of the one month follow-up MRI.
  • Randomized Portion: Occurrence of edema increase and initiation of dexamethasone (or any corticosteroid administration with the purpose of treating cerebral edema) [ Time Frame: 4 months ]
    Assessed between the time of SRS and the time of the one month follow-up MRI.


Original Primary Outcome:

  • Pilot Portion: Occurrence of Dose Limiting Toxicities (DLTs) between the time of SRS and the time of the one month follow-up MRI. [ Time Frame: 4 months ]
  • Randomized Portion: Occurrence of edema increase and initiation of dexamethasone (or any corticosteroid administration with the purpose of treating cerebral edema) between the time of SRS and the time of the one month follow-up MRI. [ Time Frame: 4 months ]


Current Secondary Outcome:

  • ktrans change [ Time Frame: 4 months ]
    Assessed at the time of SRS and the time of the one and three month post SRS MRI scans.
  • FLAIR ratio change [ Time Frame: 4 months ]
    Assessed at the time of SRS and the time of the one and three month post SRS MRI scans.
  • Time until dexamethasone initiation (or any corticosteroid administration with the purpose of treating cerebral edema) [ Time Frame: 4 months ]
    Measured between the time of SRS and the time of the one and three month post SRS MRI scans.
  • Incidence of CTCAE version 4.0 reportable toxicities of grades 2-5. [ Time Frame: 4 months ]
    Incidence of CTCAE version 4.0 reportable toxicities of grades 2-5.
  • Incidence of CTCAE version 4.0 reportable toxicities of grades 1-2 Cardiac Disorders or Hepatobiliary Disorders. [ Time Frame: Up to 4 months ]
    Incidence of CTCAE version 4.0 reportable toxicities of grades 1-2 Cardiac Disorders or Hepatobiliary Disorders.
  • Cerebral edema increase as measured on FLAIR volumetric imaging [ Time Frame: 4 months ]
    Defined from MRI taken at the time of SRS and the time of the one and three month post SRS MRI scans.
  • Absolute volume change of index tumor(s) [ Time Frame: 4 months ]
    Absolute volume change of index tumor(s) that received radiosurgery as manually contoured by the radiation oncologist defined from T1 post gadolinium sequences at the time of SRS and the time of the one and three month post SRS MRI scans.


Original Secondary Outcome:

  • ktrans change as assessed at the time of SRS and the time of the one and three month post SRS MRI scans.. [ Time Frame: 4 months ]
  • FLAIR ratio change as assessed at the time of SRS and the time of the one and three month post SRS MRI scans. [ Time Frame: 4 months ]
  • Time until dexamethasone initiation (or any corticosteroid administration with the purpose of treating cerebral edema) as measured between the time of SRS and the time of the one and three month post SRS MRI scans. [ Time Frame: 4 months ]
  • Incidence of CTCAE version 4.0 reportable toxicities of grades 2-5. [ Time Frame: 4 months ]
  • Incidence of CTCAE version 4.0 reportable toxicities of grades 1-2 Cardiac Disorders or Hepatobiliary Disorders. [ Time Frame: Up to 4 months ]
  • Cerebral edema increase as measured on FLAIR volumetric imaging, defined from MRI taken at the time of SRS and the time of the one and three month post SRS MRI scans. [ Time Frame: 4 months ]
  • Absolute volume change of index tumor(s) that received radiosurgery as manually contoured by the radiation oncologist defined from T1 post gadolinium sequences at the time of SRS and the time of the one and three month post SRS MRI scans. [ Time Frame: 4 months ]


Information By: University of Alabama at Birmingham

Dates:
Date Received: May 28, 2015
Date Started: May 2017
Date Completion: October 2019
Last Updated: April 28, 2017
Last Verified: April 2017