This is a Phase 2, open-label, single arm, multicenter, 2-stage study of eribulin mesylate
administered biweekly at 1.4 mg/m2 intravenously for the treatment of participants with
HER2-negative metastatic breast cancer previously treated with 2 to 5 chemotherapy regimens.
The study will be conducted in 3 Phases: a Pretreatment Phase (screening visit), a Treatment
Phase (starting with Cycle 1 Day 1), and a Posttreatment Phase (End of treatment visit and
survival follow up). Participants may remain on study drug as long as they demonstrate
clinical benefit or until intercurrent illness, unacceptable toxicity, or disease progression
occurs, until the participant withdraws consent, or death.
Inclusion Criteria:
1. Histological or cytological adenocarcinoma of the breast.
2. Females, aged greater than or equal to 18 years at time of informed consent.
3. HER2-negative as determined by fluorescence in situ hybridization (FISH); or 0 or 1+
by immunohistochemistry (IHC) staining .
4. Participants with metastatic breast cancer who have received at least 2 and not more
than 5 prior chemotherapy regimens.
5. Participants with at least one measurable lesion greater than or equal to 10 mm in the
longest diameter for a non-lymph node or greater than or equal to 15 mm in the
short-axis diameter for a lymph node as determined by investigator using Response
Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).
6. Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2.
7. Life expectancy of greater than or equal to 3 months.
8. Any neuropathy must recover to Grade less than or equal to 2 prior to enrollment.
9. Adequate renal function as evidenced by serum creatinine less than or equal to 1.5
mg/dL or calculated creatinine clearance greater than or equal to 50 mL/minute
according to the Cockcroft and Gault formula.
10. Adequate bone marrow function as evidenced by absolute neutrophil count (ANC) greater
than or equal to 1.5 X 10^9/L, hemoglobin greater than or equal to 10.0 g/dL (can be
corrected by growth factor or transfusion), and platelet count greater than or equal
to 100 X 10^9/L.
11. Adequate liver function as evidenced by total bilirubin less than or equal to 1.5 X
upper limit of normal (ULN), alkaline phosphatase, alanine aminotransferase (ALT), and
aspartate aminotransferase (AST) less than or equal to 3 X ULN (less than or equal to
5 X ULN in the case of liver metastases), unless there are bone metastases, in which
case liver specific alkaline phosphatase must be separated from the total and used to
assess the liver function instead of the total alkaline phosphatase.
12. Are willing and able to comply with all aspects of the treatment protocol.
13. Provide written informed consent.
Exclusion Criteria:
1. Previous treatment with eribulin.
2. Hypersensitivity to eribulin/excipients or halichondrin B or known intolerance of
eribulin.
3. Current enrollment in another clinical study or used of any investigational drug or
device within the past 28 days preceding informed consent.
4. Previous treatment with chemotherapy, radiation, biological, or targeted therapy
within the last 2 weeks or 5 X half-life, whichever is longer, preceding informed
consent.
5. Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a
positive beta-human chorionic gonadotropin ([B-hCG] test). A separate Baseline
assessment is required if a negative screening pregnancy test was obtained more than
72 hours before the first dose of study drug.
6. All females will be considered to be of childbearing potential unless they are
postmenopausal (amenorrheic for at least 12 consecutive months, in the appropriate age
group, and without other known or suspected cause) or have been sterilized surgically
(ie, bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with
surgery at least 1 month before dosing).
7. Females of childbearing potential who had unprotected sexual intercourse within 30
days before study entry and who do not agree to use a highly effective method of
contraception (eg, total abstinence, an intrauterine device, a double-barrier method
[such as condom plus diaphragm with spermicide], a contraceptive implant, an oral
contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout
the entire study period or for 28 days after study drug discontinuation.
Females who are currently abstinent and do not agree to use a double barrier method as
described above or to refrain from sexual activity during the study period or for 28
days after study drug discontinuation.
Females who are using hormonal contraceptives but are not on a stable dose of the same
hormonal contraceptive product for at least 4 weeks before dosing and who do not agree
to use the same contraceptive during the study or for 28 days after study drug
discontinuation.
8. Known central nervous system (CNS) disease, except for those participants with treated
brain metastasis who are stable for at least 1 month with no evidence of progression
or hemorrhage after treatment and no ongoing requirement for corticosteroids.
9. Known human immunodeficiency virus (HIV) positive.
10. Existing anticancer, therapy-related toxicities of Grades greater than or equal to 2,
with the exception of alopecia.
11. A prior malignancy other than carcinoma in situ of the cervix, or nonmelanoma skin
cancer, unless the prior malignancy was diagnosed and definitively treated greater
than 5 years previously with no subsequent evidence of recurrence.
12. Clinically significant cardiovascular impairment (congestive heart failure of New York
Heart Association [NYHA] Classification greater than II, unstable angina, myocardial
infarction within the past 6 months, or serious cardiac arrhythmia).
13. Clinically significant ECG abnormality, including a marked Baseline prolonged QT/QTc
interval (ie, a repeated demonstration of a QTc interval greater than 500
milliseconds).
14. Pulmonary lymphangitic involvement that resulted in pulmonary dysfunction requiring
active treatment, including the use of oxygen.
15. History of concomitant medical condition(s) that, in the opinion of the investigator,
would compromise the participant's ability to safely complete the study.
16. The investigator's belief that the participant is medically unfit to receive eribulin
or unsuitable for any other reason.
