Trial of Eribulin in Patients Who Do Not Achieve Pathologic Complete Response (pCR) Following Neoadjuvant Chemotherapy
Condition: Metastatic Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Eribulin; Trastuzumab
Intervention description: 1.4 mg/m^2 IV Days 1 and 8, every 21 days for six cycles; 6 mg/kg IV Day 1 every 21 days
Intervention MeSH terms: Trastuzumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 127.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Metastatic Breast Cancer; Adjuvant; Residual Disease; eribulin; Trastuzumab

Summary:

      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.
    

Eligibility criteria:

        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.