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

NCT ID: NCT02460874

Last Updated: 2022-09-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-16
• Study Completion Date: 2021-05-19

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 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.

Conditions

Cerebral Edema; Brain Metastases

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Glyburide

Intervention Type: DRUG

1.25mg, twice a day

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.

Group Type: PLACEBO_COMPARATOR

Glyburide

Intervention Type: DRUG

1.25mg, twice a day

Placebo

Intervention Type: OTHER

1.25mg, twice a day

Interventions

Glyburide

1.25mg, twice a day

Intervention Type: DRUG

Placebo

1.25mg, twice a day

Intervention Type: OTHER

Eligibility Criteria

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.

• 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).
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Drexell Hunter Boggs

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Alabama at Birmingham (UAB) Department of Radiation Oncology

Birmingham, Alabama, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

IRB-16063003

Identifier Type: -

Identifier Source: org_study_id