Treatment of Brain Metastases From Breast Cancer With Eribulin Mesylate

Phase 2

Completed

Conditions: Brain Metastases
Metastatic Breast Cancer

Interventions: Drug: Eribulin Mesylate
Device: MRI

Registration Number: NCT02581839

Lead Sponsor: Case Comprehensive Cancer Center

Brief Summary: Subjects are asked to take part in a clinical research study that tests Eribulin, a new drug. Eribulin is an investigational (experimental) anti-cancer agent that has not been approved by the Food and Drug Administration (FDA) for use in patients with brain metastases. Eribulin is FDA approved for use in patients with metastatic breast cancer but the effect it may or may not have on brain metastases has not been studied.

Detailed Description: Primary Objectives:

To determine the 3-month central nervous system (CNS)-progression free survival (PFS) for patients with metastatic breast cancer with brain metastases treated with eribulin mesylate.

Secondary Objective(s):

1. Estimate CNS complete and partial response rates (CR and PR) and duration of CNS response in this patient population.

2 Evaluate toxicity in patients with breast cancer with brain metastases treated with eribulin mesylate.

3 Estimate clinical benefit rate (CBR) at 3 months in breast cancer patients with brain metastases treated with eribulin mesylate. (CBR is the sum of CR, PR and stable disease at 3 months).

4 To estimate systemic disease (extra cranial) response rate and duration of systemic response in this patient population.

5 Overall survival in this patient population.

Design:

This is a phase II study that will require patients to evaluate the primary objective (CNS PFS at 3 months). Study patients will have a baseline brain MRI and a second MRI at 12 weeks to evaluate disease.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 9

Inclusion Criteria

Female with histologically confirmed breast cancer.
Patients must have evidence of metastatic disease (non measurable disease is eligible).
Radiologically confirmed metastatic brain lesion by MRI.
Brain metastases from breast cancer with or without prior WBRT, STS of surgical resection. Progression must be documented in an at least one lesion untreated by SRS or in any site after surgery or WBRT.
Patients must be neurologically stable and with stable dose steroids and anticonvulsants for at least 1 week prior to obtaining the baseline MRI of the brain, and/or at least 1 week prior to beginning study treatment.
No presence of uncontrolled systemic disease or tumor related complication which, in opinion of the investigator, might restrict life expectancy to less than 3 months.
Patients may not be on any cytotoxic chemotherapy or hormonal treatment for breast cancer during protocol treatment. Trastuzumab is allowed in HER2 positive patients).
Able to comprehend and willing to sign an Informed Consent Form (ICF)
Karnofsky performance status ≥ 60
No brain radiation therapy > 4 weeks
No chemotherapy for > 3 weeks before planned start of protocol treatment
Adequate bone marrow, renal, and hepatic function, per local reference laboratory ranges as follows:
- Absolute neutrophil count (ANC) ≥ 1,500/mm3
- Platelet count ≥ 100,000/mm3
- Hemoglobin ≥ 9 g/dL
- Calculated creatinine clearance (CrCl) ≥ 30mL/min (Cockcroft-Gault method)
- Patients with normal, mild or moderate hepatic dysfunction are eligible.
- Calcium <10.1 mg/dL (corrected to serum albumin as follows: Corrected Calcium = (0.8 x (4 - patient albumin)) + serum Ca
Females of child-bearing potential must have a negative pregnancy test at screening and agree to take appropriate precautions to avoid pregnancy (double barrier method of birth control or abstinence) from screening through 3 months after the last dose of treatment
Able to undergo MRI evaluation with and without gadolinium contrast

Exclusion Criteria

Patients with the presence of an active infection, abscess or fistula
Known leptomeningeal disease or CNS midline shifts.
Any evidence of severe or uncontrolled systemic disease such as clinically significant cardiovascular, pulmonary, hepatic, renal or metabolic disease.
Severe conduction abnormality including significant QTc prolongation >450ms.
Patients with grade 3/4 peripheral neuropathy.
Patients with pacemaker or an ICD devices.
Previous treatment with eribulin mesylate.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Eribulin Mesylate	MRI	The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate
Eribulin Mesylate	Eribulin Mesylate	The recommended starting dose of eribulin mesylate is 1.4 mg/m2 administered intravenously over 2 to 5 minutes on Days 1 and 8 of a 21-day cycle. An MRI will be completed at week 1, week 12 and every 12 weeks after cycles 4+ while on study eribulin mesylate

Primary Outcome Measures

Name	Time	Method
Percent of Participants With Central Nervous System (CNS) Progression Free Survival (PFS)	At 12 weeks	The study team will assess the percent of participants without CNS progression at 3 months. The study team will generate a Kaplan- Meier curve of CNS PFS and estimate the PFS and 95% confidence interval (CI) of the PFS. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.

Secondary Outcome Measures

Name	Time	Method
Objective Response Rate (RR)	up to 2 years from start of treatment	The study team will calculate the percent of participants with complete and partial response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.
Number of Patients Treated With Eribulin Who Experienced Serious Adverse Events	up to 2 years from start of treatment	The study team will evaluate rates (and 95% CI) of toxicity in patients treated with eribulin.
Median Duration of CNS Response	up to 2 years from start of treatment	The study team will calculate the duration of CNS response. Response and progression by MR were evaluated using WHO/modified McDonald's criteria.
Systemic Disease Response Rate	up to 2 years from start of treatment	The study team will estimate systemic disease response rate (and 95% CI) and perform a Kaplan-Meier analysis for systemic response in this patient population
Median Overall Survival (OS)	up to 2 years from start of treatment	The study team will generate a Kaplan-Meier curve of OS.
Number of Patients With CBR	At 12 weeks	The study team will sum the proportion of the patients with complete response, partial response and stable disease at 12 weeks (CBR)

Trial Locations

Locations (2): University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
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Cleveland, Ohio, United States
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
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Cleveland, Ohio, United States