Systemic and Local Levels of Lidocaine During Surgery for the Removal of Glioblastoma

Glioblastoma Clinical Trial

Official title:

Assessing Systemic and Local Levels of Lidocaine During Surgery for Glioblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04716699
• Other study ID #: UCDCC#285
• Secondary ID: NCI-2020-14099UC
• Status: Completed
• Phase: Phase 1
• Start date: January 20, 2021
• Est. completion date: January 24, 2022

Study information

• Verified date: February 2023
• Source: University of California, Davis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This clinical trial measures the amount and effect of lidocaine injected into patients with glioblastoma while they are undergoing surgical removal of their brain tumors. Lidocaine is a substance used to relieve pain by blocking signals at the nerve endings in skin. Information gained from this study may help researchers come up with new treatments to help patients with glioblastomas in the future.

Description:

PRIMARY OBJECTIVE:

I. To assess the pharmacokinetic properties of intravenously administered lidocaine inside a glioblastoma tumor by means of mass spectroscopy.

SECONDARY OBJECTIVE:

I. To assess the differences in overall survival (OS) and progression free survival (PFS) between the patients in the lidocaine therapy group and historical controls taken from the literature (Stupp et al) with comparable post-operative treatment regimen.

OUTLINE:

Patients receive bolus lidocaine intravenously (IV) per standard of care. After intubation, patients receive another infusion of lidocaine IV over 4 hours or until the end of surgery. Patients also undergo collection of blood and tumor samples at the start of surgery and hourly afterwards until a total of 4 samples are collected.

After completion of surgery, patients are followed for 24 hours, and at 7-14 days, up to 30 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 24, 2022
• Est. primary completion date: December 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• >= 18 years of age

• Preoperative imaging characteristics consistent with brain glioblastoma (magnetic resonance imaging [MRI] brain)

• Patients who are undergoing neurosurgical resection for treatment of glioblastoma

• Ability to understand and willingness to sign an informed consent form

• Ability to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria:

• Prior treatment for glioblastoma

• Glioblastoma size less than 5 cm^3

• Known allergy against amide type of local anesthetics

• History of severe cardiac failure (determined by clinical history of less the 3 Metabolic Equivalent of Tasks [METs])

• 2nd or 3rd degree heart block (exception: patients with pacemaker)

• Concurrent treatment with class I or III antiarrhythmics (phenytoin, procainamide, propranolol, quinidine) or amiodarone use =< 3 months

• History of Wolff-Parkinson-White syndrome, Stokes Adams syndrome, or active dysrhythmia

• History of bradycardia

• Prior clinical history of severe hepatic impairment or alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 1.55 times of upper normal limit

• Prior clinical history of severe renal impairment or estimated glomerular filtration rate (EGFR) < 30ml/min

• Uncontrolled seizure disorder

• Acute porphyria

• Patients requiring an awake fiberoptic intubation due to administration of additional lidocaine

• Pregnant or lactating women

• Any condition that would prohibit the understanding or rendering of informed consent

• Any medical condition including additional malignancies, laboratory abnormalities, or psychiatric illness that in the opinion of the investigator would prevent the subject from participating and adhering to study related procedures

• Uncontrolled concomitant disease that in the opinion of the investigator would interfere with the patient's safety or compliance on trial

Related Conditions & MeSH terms

• Glioblastoma

Intervention

Procedure:
• Biospecimen Collection
Undergo collection of blood and tumor samples

Drug:
• Lidocaine
Given IV

Procedure:
• Resection
Undergo surgical resection per standard of care

Locations

Country	Name	City	State
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California

Sponsors (2)

Lead Sponsor	Collaborator
Kiarash Shahlaie, M.D., Ph.D.	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference between the concentrations of lidocaine in the tumor tissue and in the blood (baseline level)	Analysis is mainly descriptive and will be mainly done by Lidocaine analysis lab. Will report the mean and standard deviation of concentration of lidocaine in the tumor and blood at 3 time points. The pharmacokinetics of lidocaine within the tumor will be summarized using the means, and standard pharmacokinetics parameters will be reported (maximum concentration, time of maximum concentration, and area under the curve). If applicable, will use mixed effects model to summarize trajectories of change for concentration measured at multiple time points, which will account for correlation between repeated measures within patient.	At start of surgery up until completion of surgery, assessed up to 4 hours after starting surgery
Secondary	Progression free survival (PFS)	Kaplan-Meier plots and confidence intervals will be used to summarize PFS. Medians (and associated 95% confidence intervals) of PFS will then be calculated and compared with historical control from the literature.	From diagnosis to first documented evidence of disease progression or death, whichever comes first, assessed up to 30 days after surgery
Secondary	Overall survival (OS)	Kaplan-Meier plots and confidence intervals will be used to summarize OS. Medians (and associated 95% confidence intervals) of OS will then be calculated and compared with historical control from the literature.	From diagnosis to death, assessed up to 30 days after surgery
Secondary	Incidence of adverse events (AEs)	Will record safety and toxicity profile using National Cancer Institute Common Terminology Criteria for Adverse Events 5.0. AEs will be summarized using descriptive statistics. The type, grade, frequency and proportion of toxicities will be reported, along with associated 95% confidence interval of proportion.	Up to 30 says after surgery