Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy
Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy
The investigators propose to evaluate eribulin as adjuvant therapy in breast cancer patients
 who have residual invasive disease in breast or lymph node tissue following standard
 neoadjuvant chemotherapy and surgery regimen. Three cohorts of patients will be evaluated
 separately based on tumor type: triple-negative, hormone-receptor-positive/HER2-negative, and
 HER2-positive breast cancers.
This is a non-randomized, open-label trial to evaluate 6 cycles of eribulin in female
 patients with invasive breast cancer who do not achieve pathologic complete response (pCR)
 after treatment with a standard neoadjuvant chemotherapy and surgery regimen. Patients will
 be randomized into three cohorts according to tumor-type: triple-negative (Cohort A),
 hormone-receptor-positive/HER2-negative (Cohort B), and HER2-positive (Cohort C) tumors.
 Patients will receive eribulin for 6 cycles (1 cycle = 21 days). Patients with HER2-positive
 tumors will also receive trastuzumab. Patients in all cohorts will be allowed to receive
 locoregional radiotherapy and/or adjuvant hormonal therapy per institutional guidelines.
Inclusion Criteria:

 1. Female patients >=18 years-of-age.

 2. Histologically confirmed breast cancer prior to surgery with the following staging
 criteria: T1-T3, T4a, T4b, N0-N2, N3a and M0 (T1N0M0 patients are excluded).
 Inflammatory disease is 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
 dissection.

 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/T1a, 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 v4.0) except
 fatigue or alopecia.

 8. Peripheral neuropathy Grade <=2 per NCI CTCAE v4.0 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 (HER2-positive).

 10. Adequate hematologic, hepatic, and renal function

 11. 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.

 12. 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.

 13. Willingness and ability to comply with trial and follow-up procedures.

 14. Ability to understand the investigative nature of this trial and give written informed
 consent.

 15. 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.

 Exclusion Criteria:

 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
 disease.

 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 pregnancy test within 48 hours prior to trial treatment.

 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
 formula).

 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
 treatment.

 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.