NCT03971734

Determining Dose of Regadenoson Most Likely to Transiently Alter the Integrity of the Blood-Brain Barrier in Patients With High Grade Gliomas

Determining the Dose of Regadenoson Most Likely to Transiently Alter the Integrity of the Blood-Brain Barrier in Patients With High Grade Gliomas

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 7 (actual)
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Not accepted

Summary

enroll patients with histologically confirmed high-grade gliomas to evaluate the ability of regadenoson to transiently disrupt a relatively intact blood-brain barrier (BBB). determine the best dose of regadenoson to disrupt the BBB and allow for enhanced penetration of gadolinium during MRI.

Detailed description

PRIMARY OBJECTIVE: To determine if there is a dose of regadenoson, in the range shown to be safe for clinical administration, that can increase gadolinium Ktrans by more than 10 times the values reported in the literature within normal-appearing brain parenchyma with a previously documented intact blood-brain barrier in patients with high grade gliomas. SECONDARY OBJECTIVE To determine if there is a dose of regadenoson, in the range shown to be safe for clinical administration, that can substantially alter the normalized, contrast enhanced MRI signal intensity in normal-appearing tissues and in: A) Brain adjacent to tumor (i.e. T2 hyperintense, but without contrast enhancement before regadenoson) and B) Contrast enhancing tumor (with contrast enhancement before regadenoson). Part I Treatment Plan Part I of the protocol is designed to identify the best regadenoson dose(s) to transiently disrupt the blood-brain barrier as measured by DCE-MRI and contrast enhancement on T1-weighted images corresponding to an increase in the accumulation of MRI contrast (gadolinium) into normal appearing brain contralateral to the brain tumor. Patients who are at low risk of having complications with a standard regadenoson cardiac stress test (young with no known cardiac disease) and who have had stable MRI scans for at least 2 months prior to enrollment will be asked to undergo a research MRI within two weeks after their most recent previous MRI. Part II Treatment Plan Part II will be initiated if the first portion of the study identifies one or more doses of regadenoson that meets the desired endpoint of a Ktrans value \>0.04 min-1 within contralateral normal-appearing brain following regadenoson administration. Part II patients will undergo more extensive imaging prior to regadenoson administration to confirm that regadenoson has a significant effect on the BBB using a more comprehensive imaging approach. Five additional patients who are at low risk to have complications of a standard chemical cardiac stress test (young with no known significant cardiac disease) will be sequentially enrolled at each regadenoson dose meeting the desired endpoint in Part I. In these cohorts, the full research imaging protocol will be utilized in both the pre- and post-regadenoson MRI scans which will allow a direct comparison of all imaging parameters in both the pre-regadenoson and post-regadenoson settings to be directly compared.

Conditions

• High Grade Glioma
• Anaplastic Astrocytoma
• Anaplastic Oligodendroglioma
• Glioblastoma

Interventions

Type	Name	Description
DRUG	Regadenoson 0.05mg	Regadensoson 0.05mg administered prior to MRI
DRUG	Regadensoson 0.1mg	Regadensoson 0.1mg administered prior to MRI
DRUG	Regadensoson 0.2mg	Regadensoson 0.2mg administered prior to MRI
DRUG	Regadensoson 0.4mg	Regadensoson 0.4mg administered prior to MRI
DRUG	Regadensoson 0.7mg	Regadensoson 0.7mg administered prior to MRI
DRUG	Regadensoson 1.0mg	Regadensoson 1.0mg administered prior to MRI
DRUG	Regadensoson 1.4mg	Regadensoson 1.4mg administered prior to MRI

Timeline

• Start date: 2019-12-06
• Primary completion: 2022-04-30
• Completion: 2023-10-02
• First posted: 2019-06-03
• Last updated: 2023-10-06

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study