Eribulin Mesylate in Treating Patients With Previously Treated Metastatic Breast Cancer

PRIMARY OBJECTIVES:

I. Progression free survival (PFS).

SECONDARY OBJECTIVES:

I. Frequency of alopecia with absence or decrease to < 50%.

II. Incidence of grade 3 and 4 neutropenia of < 30%.

III. Incidence of sensory neuropathy (all grades) to < 25%.

TERTIARY OBJECTIVES:

I. Assess the role of circulating endothelial cell precursors (CEPs) and apoptotic
circulating endothelial cells (CECs), in predicting early response to treatment.

OUTLINE:

Patients receive eribulin mesylate intravenously (IV) over 2-5 minutes on days 1, 8, and 15.
Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 1 year.

Inclusion Criteria:

- Ability to provide written informed consent

- Prior exposure to taxane in the adjuvant, neoadjuvant or metastatic setting

- At least one prior regimen of chemotherapy in the setting of metastatic breast cancer;
no upper limit on the number of prior endocrine regimens for metastatic breast cancer,
however no more than 6 chemotherapeutic regimens may have been given in the metastatic
setting

- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

- Patients must have baseline imaging within 30 days prior to the start of therapy and
satisfy one of the following:

- Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
criteria

- At least one non lymph node lesion of >= 1.0 cm or lymph node >= 1.5 cm in short
axis by computerized tomography (CT) scan (CT scan thickness no greater than 5 mm
which is serially measurable according to RECIST 1.1 using either computerized
tomography (CT) or magnetic resonance imaging (MRI)

- Lesions that have had radiotherapy must show evidence of progressive disease (PD)
based on RECIST 1.1 to be deemed a target lesion

- Non-measurable disease by RECIST 1.1 criteria (includes bone only disease and
lesions < 10 mm or lymph nodes < 15 mm in short axis) with rising serum CA15-3 or
CA 27.29 or CEA documented by two consecutive measurements taken at least 14 days
apart with the most recent measurement being within 42 days prior to
registration. The second CA 15-3 or CA 27.29 value must have at least a 20%
increase over the first and for CA 15-3 or CA27.29 be greater than or equal to 40
units/mL or for CEA be greater than or equal to 4 ng/mL

- Absolute neutrophil count >= 1,500/mm^3

- Hemoglobin >= 10 g/dL

- Platelets >= 100,000/mm^3

- Creatinine =< 1.5 x upper limit of normal (ULN)

- Total bilirubin =< 1.5 x ULN

- Alkaline phosphatase =< 3.0 x ULN; up to 5 x ULN is acceptable if due to bone
metastases in the absence of liver metastases

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x
institutional upper limit of normal, unless due to liver metastases (=< 5 x ULN)

- Women of child-bearing potential (WOCBP) and men must agree to use adequate
contraception (hormonal or barrier method of birth control or abstinence) prior to
study entry and for the duration of study participation

- Life expectancy of > 12 weeks

Exclusion Criteria:

- Prior treatment with eribulin

- Plan to administer any other systemic antitumor including endocrine therapy except for
following standard of care treatment:

- Trastuzumab at standard dosing human epidermal growth factor receptor 2 (HER2)
positive tumors

- Denosumab or bisphosphonates to treat metastatic bone disease

- Plan to administer concurrent radiation therapy now or for progressive symptoms during
treatment

- Patients with known central nervous system (CNS) metastases must have stable disease
off steroids after treatment with surgery or radiation therapy

- Second primary malignancy that is clinically detectable or clinically significant at
the time of consideration for study enrollment

- Patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic and/or moderate
(creatinine clearance [CrCl] 30-50 mL/min) renal impairment

- Radiotherapy within 14 days of study treatment

- Major surgery within 21 days of study treatment; minor surgery within 2 weeks of study
treatment; placement of vascular access device and biopsies allowed and is not
considered major or minor surgery

- Treatment with any systemic chemotherapy or investigational agents within 3 weeks of
the start of study treatment; endocrine treatment must be stopped prior to initiating
study treatment; subjects must have recovered from toxicities of prior therapy

- Patients with peripheral neuropathy > grade 2 regardless of etiology

- Significant cardiovascular impairment: congestive heart failure > class II according
to the New York Heart Association (NYHA), unstable angina or myocardial infarction
within 6 months of enrollment, or serious cardiac arrhythmia (> grade 2)

- Concomitant severe or uncontrolled medical disease

- Significant psychiatric or neurologic disorder which would compromise participation in
the study

- Pregnant or breast-feeding females