Brain Interstitium Temozolomide Concentration Pre and Post Regadenoson Administration

Completed · Early Phase 1

Conditions studied: Blood Brain Barrier Defect

In brief

The blood-brain barrier (BBB) is an intricate barrier composed of a variety of efflux pumps, a luminal negative charge, a basal lamina and three distinct cell types: brain endothelial cells, pericytes, and astrocyte foot processes. Specifically, the BBB integrity and degree of permeability is regulated by the capillary endothelial cells in response to astrocytic signals. The strength of intercellular junctions (ex. tight junctions, adherins) amongst endothelial cells also plays a major role in permeability. Therefore, modulation of all these paracellular properties may decrease BBB integrity and thus improve drug penetration to the tumor bed. Previous studies utilizing the vasoactive peptide, Regadenoson, demonstrated transient increase in BBB permeability, allowing a 70kD dextran molecule to enter the brain of rodents. Thus, the investigators propose to evaluate brain interstitium concentrations of temozolomide pre and post Regadenoson using brain microdialysis. If Regadenoson successfully demonstrates effectiveness in disrupting the BBB, it could be of major importance in improving the outcome of patients with a variety of brain tumors and other neurologic illnesses.

Key facts

Study ID

NCT02389738

Run by

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

People needed

6

Starts

2015-02-01

Expected to finish

2018-02-01

Last updated by the study team

2018-11-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Age ≥ 18
• Diagnosis of recurrent high grade glioma confirmed by frozen pathology intra-operatively
• Patients with planned surgical debulking or biopsy
• Karnofsky performance status (KPS) ≥ 60%
• Mini Mental Status Exam ≥ 15
• Adequate hepatic function
• Total bilirubin ≤ 1.8 mg/dL
• Serum levels of aspartate aminotransferase ≤ 3x the institutional upper limit of normal
• Adequate renal function
• Serum creatinine ≤ 1.5mg/dL
• Adequate bone marrow function
• ANC ≥ 1500 cells/mm3
• Platelet count ≥ 100,000 cells/mm3

You may not qualify if…

• Currently receiving chemotherapy, or radiation therapy
• Allergic to temozolomide
• Pregnant or breast-feeding
• Have a serious medical or psychiatric illness or social situation that could interfere with catheter placement or monitoring
• Prior use of VEGF or VEGFR-targeted therapy
• Use of medications: Vincristine, Vinblastine, Rifampin, Opioid's, Antidepressants within the past 24 hours
• Use of investigational agents within the past 4 weeks
• NCI CTC Grade 3 or greater baseline neurologic symptoms
• History of cardiac disease:
• Atrial fibrillation or uncontrolled tachyarrhythmia, or advanced atrioventricular block (second or third degree heart block)
• History of sinus node dysfunction
• History of symptomatic sinus bradycardia or recorded (heart rate <40/minute)
• Use of dipyridamole, dipyridamole-containing medications
• Any history of coronary heart disease defined by prior myocardial infarction or ischemia on cardiac stress testing or coronary stenosis ≥50% severity
• Moderate or severe aortic stenosis
• Uncontrolled hypertension (BP >200/110)
• Decompensated or inadequately controlled congestive heart failure.
• Acute pulmonary embolism
• Acute myocarditis or pericarditis
• Acute aortic dissection
• Severe pulmonary hypertension
• Hypertrophic obstructive cardiomyopathy
• Electrolyte abnormalities
• Unexplained chest pain that may be anginal in nature
• Use of sublingual nitroglycerin

Where it is running

• Johns Hopkins Hospital — Baltimore, Maryland, United States

Full record on ClinicalTrials.gov

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