Neuropharmacokinetics of Eribulin Mesylate in Treating Patients With Primary or Metastatic Brain Tumors

Primary Brain Tumor Clinical Trial

Official title:

An Intracerebral Microdialysis Study to Determine the Neuropharmacokinetics of Eribulin in Patients With Brain Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02338037
• Other study ID #: 14312
• Secondary ID: NCI-2014-0239114
• Status: Completed
• Phase: Early Phase 1
• Start date: May 19, 2015
• Est. completion date: March 15, 2024

Study information

• Verified date: March 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This pilot trial studies the brain concentration of eribulin mesylate in treating patients with primary or metastatic brain tumors. Drugs used in chemotherapy, such as eribulin mesylate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Collecting small samples of brain fluids may help determine how well eribulin mesylate concentrates into the brain tumor.

Description:

PRIMARY OBJECTIVES:

I. To determine the neuropharmacokinetic (nPK) profile of eribulin (eribulin mesylate) using intracerebral microdialysis.

SECONDARY OBJECTIVES:

I. To compare concentrations of eribulin in tumor (enhancing tissue) and normal brain (non-enhancing tissue) when technically feasible to place two microdialysis catheters in a study patient.

II. To describe the intracerebral clinical benefit (defined as stable disease, partial response, or complete response) of eribulin in study patients who continue to be treated with eribulin after completing the microdialysis portion of the study.

III. To document the toxicity of eribulin in the cohort of patients.

OUTLINE:

Patients undergo tumor resection or biopsy and have microdialysis catheter placed on day 0. Beginning at least 24 hours later, patients receive eribulin mesylate intravenously (IV) over 2-5 minutes on day 1. Serial brain fluid samples are collected for approximately 72 hours and the microdialysis catheter is then removed. Beginning at least 2 weeks after tumor resection or biopsy, patients may continue to receive eribulin mesylate IV over 2-5 minutes on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: March 15, 2024
• Est. primary completion date: August 4, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have a Karnofsky performance status of >= 60

• Brain tumor patient is planning to undergo tumor resection or biopsy for the purpose of differentiating between tumor progression versus treatment-induced effects following radiation therapy and/or chemotherapy

• If a patient has magnetic resonance imaging (MRI) findings consistent with tumor but does not already have a histopathologic diagnosis of cancer, s/he may sign the consent form, but final eligibility for study enrollment will be determined based on results of the frozen section at time of surgery

• Patient may have received previous treatment for the brain tumor(s), including radiation (focal brain radiation, whole brain radiation or stereotactic radiosurgery), surgery or chemotherapy

• There is no limit to the number of prior chemotherapies

• Patients who have previously been treated with eribulin are allowed to participate in the microdialysis portion of the study only

• Absolute neutrophil count of > 1500 cells/mm^3

• Platelet count > 100,000 cells/mm^3

• Total bilirubin < 2.0 mg/dl

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 3 times the institutional upper limit of normal

• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3 times the institutional upper limit of normal

• Serum creatinine < 1.5 x the institutional upper limit of normal

• All subjects must have the ability to understand and the willingness to sign a written informed consent

• Patients must have sufficiently recovered (=< grade 1) from any toxicity of prior therapy; the required waiting period between the last dose of the most recent chemotherapy agent and the first dose of eribulin will be determined based on the half-life of the chemotherapy agent; the minimum time between stopping prior therapy and administering the first dose of eribulin should be 3.3 half-lives with the following exceptions: an interval of at least 6 weeks must elapse since treatment with a nitrosourea and at least 4 weeks since the last dose of bevacizumab

• If corticosteroids are required for controlling cerebral edema, patients must be on a stable dose of at least 1 week prior to enrollment

• Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for 3 months following duration of study participation; women of child-bearing potential must have a negative serum pregnancy test prior to enrollment; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately

Exclusion Criteria:

• Patients who are currently receiving chemotherapy, radiation therapy or are enrolled in another therapeutic clinical trial

• Patients who have not recovered from the toxicities of prior chemotherapy or radiation

• Patients who are taking any of the prohibited medications; if a patient is willing to discontinue such a medication in order to participate in the study, then there must be an appropriate washout period, based on the half-life of the particular drug, prior to the start of the study treatment

• Clinically evident congestive heart failure > class II of the New York Heart Association (NYHA) guidelines, unstable angina or myocardial infarction within the previous 6 months

• Clinically significant cardiac arrhythmias, prolonged QT interval, congenital long QT syndrome

• Patients who cannot undergo brain magnetic resonance imaging (MRIs)

• Patients with existing grade 3 or 4 peripheral neuropathy

• Patients who have a serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol or may not be able to comply with the safety monitoring requirements of the study

• Female patients who are pregnant or breast-feeding

• Active, clinically significant serious infection requiring treatment with antibiotics, anti-virals or anti-fungals

• Non-compliance: subjects who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Related Conditions & MeSH terms

• Brain Neoplasms
• Metastatic Malignant Neoplasm in the Adult Brain
• Neoplasms
• Primary Brain Tumor

Intervention

Procedure:
• Therapeutic Conventional Surgery
Undergo tumor resection
• Biopsy
Undergo biopsy

Drug:
• Eribulin Mesylate
Given IV

Procedure:
• Microdialysis
Undergo intracerebral microdialysis

Other:
• Pharmacological Study
Correlative studies

Locations

Country	Name	City	State
United States	City of Hope Medical Center	Duarte	California

Sponsors (3)

Lead Sponsor	Collaborator
City of Hope Medical Center	Eisai Inc., National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time of maximum concentration observed (Tmax) for eribulin mesylate	Pharmacokinetic data will be summarized by using descriptive statistics and graphical methods. The pharmacokinetic parameters will be calculated on the log scale along with means and 95% confidence limits based on a t distribution.	Baseline, at 5, 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hours and then 1 week after the infusion of eribulin mesylate
Primary	Maximum concentration observed (Cmax) for eribulin mesylate	Pharmacokinetic data will be summarized by using descriptive statistics and graphical methods. The pharmacokinetic parameters will be calculated on the log scale along with means and 95% confidence limits based on a t distribution.	Baseline, at 5, 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hours and then 1 week after the infusion of eribulin mesylate
Primary	Area under the curve (AUC) for eribulin mesylate	Pharmacokinetic data will be summarized by using descriptive statistics and graphical methods. The pharmacokinetic parameters will be calculated on the log scale along with means and 95% confidence limits based on a t distribution.	Baseline, at 5, 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hours and then 1 week after the infusion of eribulin mesylate
Primary	Half-life (t1/2) for eribulin mesylate		Baseline, at 5, 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hours and then 1 week after the infusion of eribulin mesylate
Primary	Ratio of AUC of eribulin mesylate in dialysate to plasma		Baseline, at 5, 15, 30 minutes, 1, 2, 4, 6, 8, 12, 24, 48, and 72 hours and then 1 week after the infusion of eribulin mesylate
Secondary	Toxicity profile of eribulin mesylate graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0	Will be summarized in tabular form by adverse event category, grade, and attribution.	Up to 30 days
Secondary	Clinical benefit rate defined as tumor response on brain MRI results	Clinical benefit rate and associated 95% confidence limits will be calculated based on data from participants that receive at least 2 courses of eribulin mesylate.	Up to 30 days