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TerminatedNCT02460874Updated Sep 21, 2022Results posted

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

A Phase 1/2 interventional study of Glyburide and Placebo in Cerebral Edema and Brain Metastases, sponsored by University of Alabama at Birmingham. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-09-21.

Sponsored by University of Alabama at Birmingham · Phase 1/2, Interventional, and Treatment

Why this study was terminated
Slow accrual
Phase
Phase 1/2
Study type
Interventional
Enrollment
1
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study 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.

Read the detailed description

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.

02

Conditions studied

  • Cerebral Edema
  • Brain Metastases

Keywords

  • Brain Metastases
  • Stereotactic Radiosurgery
  • Glyburide
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients with newly diagnosed brain metastases deemed to be eligible for radiosurgery.
  • Subject must have cytologically or histologically confirmed malignancy (this is the original malignancy, not the brain metastases).
  • A diagnostic contrast-enhanced MRI of the brain must be performed within 60 days prior to registration. The contrast-enhancing intraparenchymal brain tumor must be well visualized.
  • History and physical with neurological examination, height, and weight within 14 days prior to registration
  • No dexamethasone use (or any other corticosteroid use with the purpose of treating cerebral edema) starting 5 days prior to SRS. Patients may be tapered to meet this criterion if deemed safe by the treating physician.
  • Women of child-bearing potential (e.g. not post-menopausal or permanently sterilized women) must have a negative pregnancy test obtained within 14 days prior to registration. This is to prevent potential harm to the fetus by glyburide and radiotherapy.
  • CBC with differential and CMP including Liver Function Tests (LFTs) obtained within 14 days prior to registration and meeting the following requirements:

    • Creatinine Clearance ≥ 50 mL/min.
    • Total Bilirubin \< 1.5 x the upper limit of normal (ULN).
    • ALT and AST ≤ 2.5 x ULN.
    • Glucose ≥ 80 mg/dL.
    • Hemoglobin ≥ 7 mg/dL.
    • Absolute Neutrophil Count > 100 cells/mm3.
  • For the Randomized Portion only: Subject must have at least 2 of the following risk factors: {For the Pilot Portion, it is not required that patients have the risk factors mentioned in Inclusion Criteria 9.}

    • Pretreatment Edema/Tumor ratio (≥ 35:1) as contoured on a baseline MRI obtained at most 60 days prior to registration. Patients are allowed to have Whole Brain Radiotherapy (WBRT) or corticosteroid use between the time of pretreatment MRI and SRS (as long as the corticosteroids can be safely tapered at least 5 days prior to the treatment planning MRI and WBRT is at least 4 days prior to registration).
    • Greater than 40 pack year history of smoking cigarettes.
    • Whole Brain Radiotherapy at least 4 days and no more than 1 year prior to registration.
    • RPA Class III.

Exclusion criteria

Exclusion Criteria:

  • Known sulfonylurea treatment within 7 days prior to registration. Sulfonylureas include glyburide/glibenclamide (Diabeta, Glynase); glyburide plus metformin (Glucovance); glimepiride (Amaryl); repaglinide (Prandin); nateglinide (Starlix); glipizide (Glucotrol, GlibeneseR, MinodiabR); gliclazide (DiamicronR); tolbutamide (Orinase, Tolinase); and glibornuride (Glutril).
  • Diffuse Leptomeningeal metastases.
  • Known allergy to sulfa or specific allergy to sulfonylurea drugs.
  • Use of VEGF inhibitors within 10 days prior to registration.
  • Allergy to gadolinium.
  • Type 1 diabetes mellitus or Type 2 diabetes mellitus actively receiving treatment.
  • Cognitive impairment that precludes a patient from acting as his or her own agent to provide informed consent.
  • Concurrent use of Bosentan.
  • Any major medical illnesses or psychiatric impairments that in the treating physician's opinion will prevent administration or completion of protocol therapy ( which may include patients who are elderly, debilitated, or malnourished persons and/or those with renal, hepatic or adrenal insufficiency).
  • Pregnant or breast feeding women due potential damage to the fetus
  • Inability to undergo MRI or SRS (e.g. due to safety reasons such as presence of a pacemaker).
  • Deemed by the treating physician to be unable to eat regular meals.
  • Patients currently on beta blockers.
  • Patients with a known diagnosis of ongoing alcoholism/alcohol abuse.
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
1 participant (actual)

Study arms

  • Experimental
    Pilot Portion

    Step 1: Patients with brain metastases requiring SRS and not taking corticosteroids 5 days prior to SRS. Treatment planning MRI may be done within 21 days prior to SRS treatment. Step 2: Take Glyburide 1.25mg (twice a day by mouth) beginning 5 days prior to SRS. Receive glucose monitoring materials and blood glucose education- begin glucose monitoring (4 times a day). Step 3: 1 week after SRS, return to clinic to review glucose logs- continue glyburide and blood glucose monitoring. Step 4: 1 month after SRS, discontinue both glyburide and blood glucose monitoring, undergo MRI. Step 5: 3 months after SRS, undergo MRI.

    Drug: Glyburide

  • Placebo comparator
    Randomized Portion

    Step 1: Patients with brain metastases requiring SRS and not taking corticosteroids 5 days prior to SRS.Treatment planning MRI may be done within 21 days prior to SRS treatment. Step 2: Randomization (1:1) * Group 1: take Glyburide (1.25mg, twice a day by mouth) beginning 5 days prior to SRS. Receive glucose monitoring materials and blood glucose education. Begin glucose monitoring (once a day) {This portion will be double blinded}. * Group 2: Take Placebo (1 pill, twice a day by mouth) beginning 5 days prior to SRS. Receive glucose monitoring materials and blood glucose education. Begin glucose monitoring (once a day) {This portion will be double blinded}. Step 3: 1 week after SRS, return to clinic to review glucose logs, continue investigation medication, but discontinue glucose monitoring. Step 4: 1 month after SRS, discontinue investigation medication, undergo MRI. Step 5: 3 months after SRS, undergo MRI.

    Drug: Glyburide · Other: Placebo

Interventions

  • DrugGlyburide

    1.25mg, twice a day

  • OtherPlacebo

    1.25mg, twice a day

05

What researchers measure

Primary outcomes

  1. Number of Participants With Dose Limiting Toxicities (DLTs)

    Assessed between the time of glyburide initiation and the time of the one month follow-up MRI.

    Time frame: 4 months

  2. Randomized Portion: Occurrence of Edema Increase and Initiation of Dexamethasone (or Any Corticosteroid Administration With the Purpose of Treating Cerebral Edema)

    Assessed between the time of SRS and the time of the one month follow-up MRI.

    Time frame: 4 months

Secondary outcomes

  1. Number of Participants Administered Dexamethasone (or Any Corticosteroid Administration With the Purpose of Treating Cerebral Edema)

    Measured between the time of SRS and the time of the one and three month post SRS MRI scans.

    Time frame: 4 months

  2. Number of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 2-5.

    Incidence of CTCAE version 4.0 reportable toxicities of grades 2-5.

    Time frame: 4 months

  3. Number of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 1-2 Cardiac Disorders or Hepatobiliary Disorders.

    Incidence of CTCAE version 4.0 reportable toxicities of grades 1-2 Cardiac Disorders or Hepatobiliary Disorders.

    Time frame: Up to 4 months

  4. Number of Participants With 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

  5. Number of Participants With Absolute Volume Change of Index Tumor(s)

    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

06

Results

Posted Sep 21, 2022

Participant flow

Participant flow — Overall Study
MilestonePilot PortionRandomized Portion
Started10
Completed10
Not completed00

Outcome measures

PrimaryNumber of Participants With Dose Limiting Toxicities (DLTs)

Assessed between the time of glyburide initiation and the time of the one month follow-up MRI.

Time frame:
4 months
Reported as:
Count of participants · Participants
Number of Participants With Dose Limiting Toxicities (DLTs)
ParticipantsPilot PortionRandomized Portion
Number of Participants With Dose Limiting Toxicities (DLTs)00
PrimaryRandomized Portion: Occurrence of Edema Increase and Initiation of Dexamethasone (or Any Corticosteroid Administration With the Purpose of Treating Cerebral Edema)

Assessed between the time of SRS and the time of the one month follow-up MRI.

Time frame:
4 months

No measurements were reported for this outcome.

SecondaryNumber of Participants Administered Dexamethasone (or Any Corticosteroid Administration With the Purpose of Treating Cerebral Edema)

Measured between the time of SRS and the time of the one and three month post SRS MRI scans.

Time frame:
4 months
Reported as:
Count of participants · Participants
Number of Participants Administered Dexamethasone (or Any Corticosteroid Administration With the Purpose of Treating Cerebral Edema)
ParticipantsPilot PortionRandomized Portion
Number of Participants Administered Dexamethasone (or Any Corticosteroid Administration With the Purpose of Treating Cerebral Edema)00
SecondaryNumber of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 2-5.

Incidence of CTCAE version 4.0 reportable toxicities of grades 2-5.

Time frame:
4 months
Reported as:
Count of participants · Participants
Number of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 2-5.
ParticipantsPilot PortionRandomized Portion
Number of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 2-5.00
SecondaryNumber of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 1-2 Cardiac Disorders or Hepatobiliary Disorders.

Incidence of CTCAE version 4.0 reportable toxicities of grades 1-2 Cardiac Disorders or Hepatobiliary Disorders.

Time frame:
Up to 4 months
Reported as:
Count of participants · Participants
Number of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 1-2 Cardiac Disorders or Hepatobiliary Disorders.
ParticipantsPilot PortionRandomized Portion
Number of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 1-2 Cardiac Disorders or Hepatobiliary Disorders.00
SecondaryNumber of Participants With 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
Reported as:
Count of participants · Participants
Number of Participants With Cerebral Edema Increase as Measured on FLAIR Volumetric Imaging
ParticipantsPilot PortionRandomized Portion
Number of Participants With Cerebral Edema Increase as Measured on FLAIR Volumetric Imaging10
SecondaryNumber of Participants With Absolute Volume Change of Index Tumor(s)

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
Reported as:
Count of participants · Participants
Number of Participants With Absolute Volume Change of Index Tumor(s)
ParticipantsPilot PortionRandomized Portion
Number of Participants With Absolute Volume Change of Index Tumor(s)00

Adverse events

Collected over 1 year. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Pilot Portion0/1 (0%)0/1 (0%)0/1 (0%)
Randomized Portion———

Baseline characteristics

terminated early

Age, Categorical
Age, Categorical(Participants)Pilot PortionRandomized PortionTotal
<=18 years000
Between 18 and 65 years101
>=65 years000
Age, Continuous
Age, Continuous(years)Pilot PortionRandomized PortionTotal
Mean41 ± 0—41 ± 0
Sex: Female, Male
Sex: Female, Male(Participants)Pilot PortionRandomized PortionTotal
Female101
Male000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Pilot PortionRandomized PortionTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American000
White101
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Pilot PortionRandomized PortionTotal
United States1—0
07

Study locations

1 site
  • University of Alabama at Birmingham (UAB) Department of Radiation Oncology
    Birmingham, Alabama 35249, United States
08

References and documents

Study documents

  • Protocol and statistical analysis plan · Jul 7, 2020
  • Informed consent form · Jul 29, 2020

Documents are hosted by the registry — open the source record to download them.

09

Registry details

Key details

Study ID
NCT02460874
Lead sponsor
University of Alabama at Birmingham
Responsible party
Drexell Hunter Boggs (Principal Investigator, University of Alabama at Birmingham) — Principal investigator
First posted
Jun 3, 2015
Start date
Aug 16, 2017
Primary completion
May 19, 2021
Completion
May 19, 2021
Results posted
Sep 21, 2022
Last update
Sep 21, 2022

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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