We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

This study is currently recruiting participants.
Verified November 2017 by Drexell Hunter Boggs, University of Alabama at Birmingham
Sponsor:
ClinicalTrials.gov Identifier:
NCT02460874
First Posted: June 3, 2015
Last Update Posted: November 29, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Drexell Hunter Boggs, University of Alabama at Birmingham
  Purpose

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.


Condition Intervention Phase
Cerebral Edema Brain Metastases Drug: Glyburide Other: Placebo Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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 Patients Receiving Radiosurgery for Brain Metastases

Resource links provided by NLM:


Further study details as provided by Drexell Hunter Boggs, University of Alabama at Birmingham:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 63
Actual Study Start Date: August 16, 2017
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: March 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pilot Portion

Step 1: Patients with 1-10 brain metastases requiring SRS and not taking corticosteroids 5 days prior to treatment planning MRI

Step 2: Take Glyburide 1.25mg (twice a day by mouth) beginning 5 days prior to treatment planning MRI. Receive glucose monitoring materials and blood glucose education- begin glucose monitoring (4 times a day)

Step 3: On day of SRS, undergo MRI for treatment planning

Step 4: 1 week after SRS, return to clinic to review glucose logs- continue glyburide and blood glucose monitoring

Step 5: 1 month after SRS, discontinue both glyburide and blood glucose monitoring, undergo MRI

Step 6: 3 months after SRS, undergo MRI

Drug: Glyburide
1.25mg, twice a day
Placebo Comparator: Randomized Portion

Step 1: Patients with 1-10 brain metastases requiring SRS and not taking corticosteroids 5 days prior to treatment planning MRI

Step 2: Randomization (1:1)

  • Group 1: take Glyburide (1.25mg, twice a day by mouth) beginning 5 days prior to treatment planning MRI. 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 treatment planning MRI. Receive glucose monitoring materials and blood glucose education. Begin glucose monitoring (once a day) {This portion will be double blinded}

Step 3: On day of SRS, undergo MRI for treatment planning

Step 4: 1 week after SRS, return to clinic to review glucose logs, continue investigation medication, but discontinue glucose monitoring

Step 5: 1 month after SRS, discontinue investigation medication, undergo MRI

Step 6: 3 months after SRS, undergo MRI

Drug: Glyburide
1.25mg, twice a day
Other: Placebo
1.25mg, twice a day

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with 1-10 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).The largest measurable brain metastasis must be at least 1.0cm in short axis dimension.
  • 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 circumscribed and must have a maximum diameter of ≤ 4.0 cm in any direction on the enhanced scan. If multiple lesions are present and one lesion is at the maximum diameter, the other(s) must not exceed 3.0 cm in maximum diameter.
  • 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 the treatment planning MRI. 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:

  • 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).
  • Leptomeningeal metastases.
  • Known allergy to sulfa or specific allergy to sulfonylurea drugs.
  • Use of VEGF inhibitors within 10 days prior to registration.
  • Patients receiving an investigational drug 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
  • Patients treated on any other therapeutic clinical protocols within 10 days prior to registration or during participation in the study.
  • 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.
  • Melanoma or renal histology
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02460874


Contacts
Contact: Kristin Webb 205-975-9316 kkwebb@uabmc.edu
Contact: Valerie Powell 205-975-9316 vpowell@uabmc.edu

Locations
United States, Alabama
University of Alabama at Birmingham (UAB) Department of Radiation Oncology Recruiting
Birmingham, Alabama, United States, 35249
Contact: Kristin Webb       kkwebb@uabmc.edu   
Contact: Valerie Powell       vpowell@uabmc.edu   
Principal Investigator: Drexell H Boggs, MD         
Sponsors and Collaborators
University of Alabama at Birmingham
  More Information

Responsible Party: Drexell Hunter Boggs, Principal Investigator, University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT02460874     History of Changes
Other Study ID Numbers: F16063003
First Submitted: May 28, 2015
First Posted: June 3, 2015
Last Update Posted: November 29, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Drexell Hunter Boggs, University of Alabama at Birmingham:
Brain Metastases
Stereotactic Radiosurgery
Glyburide

Additional relevant MeSH terms:
Neoplasm Metastasis
Brain Neoplasms
Brain Edema
Brain Diseases
Neoplasms, Second Primary
Edema
Neoplastic Processes
Neoplasms
Pathologic Processes
Signs and Symptoms
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Central Nervous System Diseases
Nervous System Diseases
Glyburide
Hypoglycemic Agents
Physiological Effects of Drugs