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Slow accrual
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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)
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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glyburide | Drug | 1.25mg, twice a day |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 4 months |
| Number of Participants With CTCAE Version 4.0 Reportable Toxicities of Grades 2-5. |
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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:
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.}
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham (UAB) Department of Radiation Oncology | Birmingham | Alabama | 35249 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Glyburide: 1.25mg, twice a day |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 7, 2020 |
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| Placebo |
| Other |
1.25mg, twice a day |
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Incidence of 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. | Incidence of 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 | Defined from MRI taken at the time of SRS and the time of the one and three month post SRS MRI scans. | 4 months |
| 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. | 4 months |
| FG001 | 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)
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. Glyburide: 1.25mg, twice a day Placebo: 1.25mg, twice a day |
| COMPLETED |
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| NOT COMPLETED |
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terminated early
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Glyburide: 1.25mg, twice a day |
| BG001 | 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)
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. Glyburide: 1.25mg, twice a day Placebo: 1.25mg, twice a day |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Patients | Posted | Count of Participants | Participants | 4 months |
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| Primary | 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. | Patients | Posted | 4 months |
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| Secondary | 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. | Patients | Posted | Count of Participants | Participants | 4 months |
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| Secondary | 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. | Patients | Posted | Count of Participants | Participants | 4 months |
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| Secondary | 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. | no patients were accrued to the randomized portion | Posted | Count of Participants | Participants | Up to 4 months |
| |||||||||||||||||||||||||||||||
| Secondary | 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. | no patients accrued to the randomized portion | Posted | Count of Participants | Participants | 4 months |
| |||||||||||||||||||||||||||||||
| Secondary | 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. | no patients accrued to the randomized portion | Posted | Count of Participants | Participants | 4 months |
|
1 year
While one patient was enrolled, this patient did not experience any AEs.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Glyburide: 1.25mg, twice a day | 0 | 1 | 0 | 1 | 0 | 1 |
| EG001 | 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)
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. Glyburide: 1.25mg, twice a day Placebo: 1.25mg, twice a day | 0 | 0 | 0 | 0 | 0 | 0 |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Hunter Boggs | UAB | 205-934-5670 | dboggs@uabmc.edu |
| May 19, 2022 |
| Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jul 29, 2020 | May 19, 2022 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D001929 | Brain Edema |
| D001932 | Brain Neoplasms |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016543 | Central Nervous System Neoplasms |
| D009423 | Nervous System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D005905 | Glyburide |
| ID | Term |
|---|---|
| D013453 | Sulfonylurea Compounds |
| D014508 | Urea |
| D000577 | Amides |
| D009930 | Organic Chemicals |
| D013450 | Sulfones |
| D013457 | Sulfur Compounds |
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| >=65 years |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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