Clinical trial NCT02581839: Treatment of Brain Metastases From Breast Cancer With Eribulin Mesylate
Official title: Treatment of Brain Metastases From Breast Cancer With Eribulin Mesylate
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Brain Metastases
Keywords: eribulin
central nervous system
CNS
Eribulin Mesylate
Halaven
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2015-10-21
Enrollment: 9
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent of Participants With Central Nervous System (CNS) Progression Free Survival (PFS)
timeFrame: At 12 weeks
Secondary outcomes:
measure: Objective Response Rate (RR)
timeFrame: up to 2 years from start of treatment
measure: Median Duration of CNS Response
timeFrame: up to 2 years from start of treatment
measure: Number of Patients Treated With Eribulin Who Experienced Serious Adverse Events
timeFrame: up to 2 years from start of treatment
measure: Number of Patients With CBR
timeFrame: At 12 weeks
measure: Systemic Disease Response Rate
timeFrame: up to 2 years from start of treatment
measure: Median Overall Survival (OS)
timeFrame: up to 2 years from start of treatment
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
name: Paula Silverman, MD
role: PRINCIPAL_INVESTIGATOR
References: