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

NCT02460874 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: IRB-16063003
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Cerebral Edema; Brain Metastases

Keywords

Brain Metastases; Stereotactic Radiosurgery; Glyburide

Outcome Measures

Primary Outcomes (2)

• 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.

  4 months

• 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.

  4 months

Secondary Outcomes (5)

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

  4 months

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

  4 months

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

  Up to 4 months

• Number of Participants With Cerebral Edema Increase as Measured on FLAIR Volumetric Imaging

  4 months

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

  4 months

Study Arms (2)

Pilot Portion

EXPERIMENTAL

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

Randomized Portion

PLACEBO COMPARATOR

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

Glyburide DRUG

1.25mg, twice a day

Pilot Portion; Randomized Portion

Placebo OTHER

1.25mg, twice a day

Randomized Portion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

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

Birmingham, Alabama, 35249, United States

Location

MeSH Terms

Conditions

Brain Edema; Brain Neoplasms

Interventions

Glyburide

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms

Intervention Hierarchy (Ancestors)

Sulfonylurea Compounds; Urea; Amides; Organic Chemicals; Sulfones; Sulfur Compounds

Results Point of Contact

• Title: Dr. Hunter Boggs
• Organization: UAB

dboggs@uabmc.edu

205-934-5670

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 28, 2015
• First Posted: June 3, 2015
• Study Start: August 16, 2017
• Primary Completion: May 19, 2021
• Study Completion: May 19, 2021
• Last Updated: September 21, 2022
• Results First Posted: September 21, 2022

Record last verified: 2022-08

Locations

US (1)