Blood Brain Barrier Differences in Patients With Brain Tumors Undergoing Surgery

Pilot Study to Assess Heterogeneity of the Blood Brain Barrier in Patients With CNS Malignancy

This pilot research trial studies blood brain barrier differences in patients with brain tumors undergoing surgery. Studying samples of tissue and blood from patients with brain tumors in the laboratory may help doctors to understand how well drugs get into different parts of a brain tumor. This may help them to determine which types of drugs may be best for treating brain tumors.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Malignant Neoplasm in the Brain; Recurrent Brain Neoplasm; Central Nervous System Neoplasm; Localized Brain Neoplasm
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Procedure: Biospecimen Collection

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 54

Contacts and Locations

• Study Contact: Name: Clinical Trials Referral Office; Phone Number: 855-776-0015; Email: mayocliniccancerstudies@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with CNS malignancy

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Observational (biospecimen collection); 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.

Other: Laboratory Biomarker Analysis; Correlative studies; Procedure: Biospecimen Collection; Undergo collection of tissue and blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood brain barrier permeability as measured by the ratio of drugs in blood and tissue samples taken during surgery	The ratio of cefazolin and levetiracetam (or lorazepam) and gadolinium in blood taken every 20-30 minutes during surgery will be correlated with the tissue samples. Inter- and intra-subject variability over all patients will be estimated, within specific imaging features between patients, and within open biopsy specimens.	At the time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Radiographic appearance at each tissue sample location	The results of the tissue samples will be compared with the radiographic appearance at each tissue sample location. This will be primarily descriptive in nature.	At the time of surgery

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jann N. Sarkaria, M.D., Mayo Clinic

Publications and helpful links

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): September 5, 2017
• Primary Completion (Estimated): March 15, 2024
• Study Completion (Estimated): March 15, 2025

Study Registration Dates

• First Submitted: February 27, 2017
• First Submitted That Met QC Criteria: March 1, 2017
• First Posted (Actual): March 7, 2017

Study Record Updates

• Last Update Posted (Actual): February 23, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Brain Neoplasms; Nervous System Neoplasms; Central Nervous System Neoplasms
• Other Study ID Numbers: MC1671 (Mayo Clinic in Rochester); P30CA015083 (U.S. NIH Grant/Contract); NCI-2017-00299 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); 16-007782 (Other Identifier: Mayo Clinic Institutional Review Board); U54CA210180 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No