Inclusion Criteria:
1. Histologic confirmation of invasive adenocarcinoma originating in the breast.
2. Stage IV disease or Stage IIIC disease (using the 7th edition AJCC criteria) not
amenable to local therapy.
3. Radiographically measurable disease as per RECIST guidelines (version 1.1).
4. Radiographic evidence of disease progression.
5. Documentation of HER2 negative breast cancer at the time of protocol registration.
6. Known hormone receptor status at the time of protocol registration.
7. Prior systemic therapy as per the following criteria:
1. Patients must demonstrate resolution of all prior chemotherapy or
radiation-related toxicities to grade less than or equal to 1, including
peripheral neuropathy, with the exception of alopecia (any grade permissible).
2. No more than one prior chemotherapy regimen for advanced or metastatic breast
cancer is allowed. Prior chemotherapy for metastatic disease must have been
completed greater than or equal to 14 days prior to randomization.
3. Prior treatment may include a taxane in the adjuvant or neoadjuvant setting,
provided that the interval between the completion of adjuvant therapy and
disease recurrence is greater than 12 months.
4. Any number of prior hormonal therapies is allowed.
5. Any number of biologic therapies (e.g., bevacizumab) or immunotherapies is
allowed in the absence of co-administered chemotherapy and must have been
completed greater than or equal to 28 days prior to randomization.
6. Prior treatment with an investigational agent is allowed but must have been
completed greater than or equal to 28 days prior to randomization.
8. Prior local therapy as per the following criteria:
1. Minor surgical procedures must be completed greater than or equal to 7 days
prior to randomization with documentation of adequate recovery from associated
complications to grade less than or equal to 1.
2. Major surgical procedures and open biopsies must be completed greater than or
equal to 28 days prior to randomization with documentation of adequate recovery
from associated complications to grade less than or equal to 1.
3. Prior radiotherapy must be completed greater than or equal to 14 days prior to
randomization with documentation of adequate recovery from associated toxicities
to grade less than or equal to 1.
9. Concurrent supportive therapy as per the following criteria:
1. Treatment with bisphosphonates or denosumab is allowed and recommended per the
standard of care.
2. Therapeutic anticoagulation is allowed for patients on a stable dose of warfarin
or low molecular weight heparin.
10. ECOG performance status of 0, 1, or 2.
11. Life expectancy of greater than 12 weeks.
12. History of brain metastases as per the following criteria:
1. Patients with a history of resected brain metastases are eligible only if they
are asymptomatic and have stable MRI scans for 3 consecutive months, including
less than or equal to 28 days of study registration.
2. Patients who receive stereotactic radiosurgery or whole brain radiation for
brain metastases are eligible only if they are asymptomatic and have stable MRI
scans for 3 consecutive months, including less than or equal to 28 days of study
registration.
13. Adequate organ function per blood work obtained less than 7 days prior to
registration.
1. Absolute neutrophil count greater than or equal to 1500/uL.
2. Platelet count greater than or equal to 100,000/uL.
3. Hemoglobin greater than or equal to 9 g/dL.
4. Total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN)
except for unconjugated hyperbilirubinemia of Gilbert's syndrome.
5. SGOT (AST) and SGPT (ALT) less than or equal to 3 x ULN except in the case of
liver metastases, where less than or equal to 5 x ULN is allowed.
6. Creatinine less than or equal to 2.0 mg/dL or creatinine clearance greater than
50 mL/min.
7. QTc interval less than or equal to 500 msec on the baseline electrocardiogram.
8. Negative pregnancy test done less than or equal to 72 hours prior to
registration for women of childbearing potential only.
14. Ability to complete questionnaire(s) independently or with assistance.
15. Willingness to provide blood and tissue samples for correlative research purposes.
16. Ability to comprehend and respond to questions using a telephone keypad.
Exclusion Criteria:
1. Prior malignancy, other than carcinoma in situ of the cervix and non-melanoma skin
cancers, unless the prior malignancy was diagnosed and definitively treated greater
than or equal to 5 years previously, there is no subsequent evidence of recurrence,
and the patient is considered by a physician to be at less than 30% risk of relapse.
2. Any of the following because this study involves an investigational agent whose
genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are
unknown:
1. Pregnant women
2. Nursing women
3. Men or women of childbearing potential who are unwilling to employ adequate
contraception
3. Presence of a serious nonhealing wound, ulcer, or bone fracture.
4. History of CTCAE grade greater than or equal to 3 hypersensitivity to paclitaxel or
Cremophor EL.
5. Pre-existing peripheral neuropathy grade greater than or equal to 2 at registration.
6. Significant cardiovascular impairment (e.g., New York Heart Association congestive
heart failure of grade II or above, unstable angina, myocardial infarction within the
past 6 months, or serious cardiac arrhythmia).
7. Subjects with known positive HIV status.
8. History of stroke or transient ischemic attack less than or equal to 6 months prior
to registration.
9. History of uncontrolled seizures.
10. Severe or uncontrolled intercurrent illness/infection.
11. Concurrent administration of any other investigational agent considered to have
potential efficacy in the treatment of breast cancer.
12. Prior exposure to eribulin mesylate.
Minimum Eligible Age: 18 Years
Maximum Eligible Age: N/A
Eligible Gender: Both