Blood Brain Barrier Differences in Patients with Brain Tumors Undergoing Surgery

PRIMARY OBJECTIVE:

I. To define the heterogeneity of blood brain barrier (BBB) permeability by assessing drug distribution in a population of patients with central nervous system (CNS) malignancy.

SECONDARY OBJECTIVE:

I. Establish correlation of BBB permeability with radiographic appearance for study patients.

CORRELATIVE RESEARCH OBJECTIVE:

I. To utilize tumor samples to investigate mechanisms for BBB heterogeneity.

OUTLINE:

As part of pre-operative standard of care, patients receive levetiracetam by injection and cefazolin by injection. Patients are also offered lorazepam in the pre-operative area. At the time of surgery, patients undergo approximately 2 tissue biopsies from 3-4 tumor locations. This tissue is removed as part of the planned surgery, but it is also tested for research purposes. During surgery, a blood sample is collected every 20-30 minutes beginning at the time of skin incision until all of the research tumor samples have been removed. A minimum of 3 blood samples are collected up to a maximum of 12.

Inclusion criteria

• Age >= 18 years
• Clinical and radiographic evidence suggesting CNS malignancy
• Suspected newly diagnosed, local, or intracranial recurrence of primary brain tumor OR previously untreated or treated brain metastasis
• Willing to undergo a neurosurgical resection of CNS lesion at Mayo Clinic Rochester
• Able to have magnetic resonance imaging (MRI) imaging with gadolinium contrast (e.g. no cardiac pacemaker, defibrillator, renal failure)
• Females of childbearing potential must have a negative pregnancy test done =< 14 days prior to registration
• Provide written informed consent
• Willing to provide tissue and blood samples for research purposes
• Patients having a study-specific surgical planning MRI only: Creatinine (estimated glomerular filtration rate [eGFR] >= 30) (obtained =< 30 days prior to registration)

Exclusion criteria

• Vulnerable populations: pregnant women, prisoners, mentally handicapped
• Unable to undergo a biopsy of CNS lesion
• Documented drug allergy to cefazolin or levetiracetam, or other contraindication to use these drugs in the pre-operative setting (e.g., patient is already on another anti-seizure medication which precludes the clinical indication for pre-operative levetiracetam)
• Patients who are unable to swallow tablets if study drug is administered by mouth
• Patients who are at risk for impaired absorption of oral medication if study drug is administered by mouth; Note: This includes but not limited to, refractory vomiting, gastric resection/bypass, and duodenal/jejunal resection
• Pregnant or nursing women; Note: Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects with chemotherapy; there is also a potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with these drugs, so breastfeeding should be discontinued for the duration of the study