Phase II Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy
1. Female patients >=18 years-of-age.
2. Histologically confirmed breast cancer prior to surgery with the following staging
criteria: T1-T3, N0-N2, and M0 (T1N0M0 patients are excluded).
3. Previous treatment with a minimum of 4 cycles of neoadjuvant anthracycline and/or
taxane containing chemotherapy (+trastuzumab in HER2-positive patients).
4. Patients must be ≥ 21 days and ≤ 84 days from breast surgery and fully recovered.
Patients may have had mastectomy or breast conservation surgery with axillary node
5. Pathologic CR (pCR) not achieved following neoadjuvant treatment (i.e., residual
invasive breast cancer (>5 mm) in the breast or presence of nodal disease at surgery
[ypT0, N1-N3a, M0 or ypT1b-T4, N0-N3a, M0].
6. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
7. Recovery from any toxic effects of prior therapy to <=Grade 1 per the National Cancer
Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v4.03) except
fatigue or alopecia.
8. Peripheral neuropathy Grade <=2 per NCI CTCAE v4.03 at trial entry.
9. Normal left ventricular ejection fraction (LVEF), within the institutional limits of
normal, as measured by echocardiography (ECHO) or multi-gated (MUGA) scan in patients
to receive trastuzumab with eribulin (Cohort C).
10. Adequate hematologic function defined as:
- Absolute neutrophil count (ANC) >=1500/μL
- Hemoglobin (Hgb) >=9 g/dL
- Platelets >=100,000/uL
11. Adequate liver function defined as:
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5 x the
upper limit of normal (ULN)
- Total bilirubin <=1.5 x ULN (unless the patient has grade 1 bilirubin elevation
due to Gilbert's disease or a similar syndrome involving slow conjugation of
12. Adequate renal function defined as:
• Serum creatinine <=1.5 mg/dL (133 μmol/L) OR calculated 24-hour creatinine
clearance >=45 mL/min.
13. Complete staging work-up to confirm localized disease should include computed
tomography (CT) scans of the chest and abdomen/pelvis (abdomen/pelvis preferred;
abdomen accepted), a CT scan of the head or MRI of the brain (if symptomatic), and
either a positron emission tomography (PET) scan or a bone scan. (Note: a PET/CT is
acceptable for baseline imaging in lieu of CT examinations or bone scan). Negative
scans performed prior to the initiation of neoadjuvant therapy, or at any subsequent
time, are acceptable and do not need to be repeated.
14. Female patients who are not of child-bearing potential and female patients of
child-bearing potential who agree to use adequate contraceptive measures, who are not
breastfeeding, and who have a negative serum pregnancy test performed within 7 days
prior to start of trial treatment.
15. Willingness and ability to comply with trial and follow-up procedures.
16. Ability to understand the investigative nature of this trial and give written
17. Agree to delay in reconstruction in terms of implants placed in setting of expanders
until chemotherapy is completed and the patient has recovered. Expansion of
expanders may continue during trial treatment.
1. Presence of other active cancers, or history of treatment for invasive cancer <3
years prior to trial entry (except thyroid, cervical cancer). Patients with Stage I
cancer who have received definitive local treatment at least 3 years previously, and
are considered unlikely to recur are eligible. All patients with previously treated
in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of
non-melanoma skin cancer.
2. Radiotherapy prior to the start of study treatment.
3. History or clinical evidence of central nervous system metastases or other metastatic
4. Non-healed surgical wound.
5. Known or suspected allergy/hypersensitivity to eribulin.
6. Cardiac disease, including: congestive heart failure Class II-IV per New York Heart
Association classification;cardiac ventricular arrhythmias requiring anti-arrhythmic
therapy; unstable angina (anginal symptoms at rest) or new-onset angina (i.e., began
within the last 3 months), or myocardial infarction within the past 6 months.
7. Chronic use of drugs that cause QTc prolongation.Patients must discontinue use of
these drugs 7 days prior to the start of study treatment.
8. Women who are pregnant or lactating. All females of child-bearing potential must
have negative serum or urine pregnancy tests within 48 hours prior to trial
9. Patients with known diagnosis of human immunodeficiency virus (HIV), hepatitis C
virus, or acute or chronic hepatitis B infection.
10. Prolongation of heart rate-corrected QT interval (QTc) >480 msecs (using Bazett's
11. Minor surgical procedures (with the exception of the placement of port-a-cath or
other central venous access) performed less than 7 days prior to beginning protocol
12. History of cerebrovascular accident including transient ischemic attack (TIA), or
untreated deep venous thrombosis (DVT)/ pulmonary embolism (PE) within the past 6
months. Note: Patients with recent DVT/PE receiving treatment with a stable dose of
therapeutic anti-coagulating agents are eligible.
13. Patients may not receive any other investigational or anti-cancer treatments while
participating in this trial.
14. History of any medical or psychiatric condition or laboratory abnormality that in the
opinion of the investigator may increase the risks associated with the trial
participation or investigational product(s) administration or may interfere with the
interpretation of the results.
15. Inability or unwillingness to comply with trial and/or follow-up procedures outlined
in the protocol.