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

NCT02338037 | Completed Early Phase 1 DMC

• 2 other identifiers: 14312NCI-2014-02391
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic Malignant Neoplasm in the Adult Brain; Primary Brain Tumor

Outcome Measures

Primary Outcomes (5)

• 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

• 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

• 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

• 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

• 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 Outcomes (2)

• Toxicity profile of eribulin mesylate graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0

  Up to 30 days

• Clinical benefit rate defined as tumor response on brain MRI results

  Up to 30 days

Study Arms (1)

Treatment (eribulin mesylate)

EXPERIMENTAL

Patients undergo tumor resection or biopsy and have microdialysis catheter placed on day 0. Beginning at least 24 hours later, patients receive eribulin mesylate 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.

Procedure: Therapeutic Conventional Surgery; Procedure: Biopsy; Drug: Eribulin Mesylate; Procedure: Microdialysis; Other: Pharmacological Study

Interventions

Therapeutic Conventional Surgery PROCEDURE

Undergo tumor resection

Treatment (eribulin mesylate)

Biopsy PROCEDURE

Undergo biopsy

Also known as: Bx

Treatment (eribulin mesylate)

Eribulin Mesylate DRUG

Given IV

Also known as: E7389, ER-086526

Treatment (eribulin mesylate)

Microdialysis PROCEDURE

Undergo intracerebral microdialysis

Treatment (eribulin mesylate)

Pharmacological Study OTHER

Correlative studies

Also known as: pharmacological studies

Treatment (eribulin mesylate)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator
• Eisai Inc.: collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

Related Publications (1)

• Eroglu Z, Synold T, Badie B, Liu A, Chowdhury A, Kilpatrick J, Blanchard S, Portnow J. An intracerebral microdialysis study to determine the neuropharmacokinetics of eribulin in patients with metastatic or primary brain tumors. Cancer Chemother Pharmacol. 2024 Dec;94(6):807-813. doi: 10.1007/s00280-024-04711-2. Epub 2024 Oct 18.

  PMID: 39422741 DERIVED

MeSH Terms

Conditions

Brain Neoplasms

Interventions

Biopsy; eribulin; Microdialysis

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Dialysis; Chemistry Techniques, Analytical

Study Officials

• Jana Portnow, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2014
• First Posted: January 14, 2015
• Study Start: May 19, 2015
• Primary Completion: August 4, 2017
• Study Completion: March 15, 2024
• Last Updated: March 19, 2024

Record last verified: 2024-03

Locations

US (1)