Trial of Eribulin Followed by Doxorubicin & Cyclophosphamide for Her2-negative, Locally Advanced Breast Cancer
Condition: Breast Neoplasms; Breast Cancer; Breast Tumors; Cancer of the Breast; Neoplasms, Breast; Tumors, Breast
MeSH terms: Neoplasms; Breast Neoplasms
Intervention: Eribulin; Doxorubicin; Cyclophosphamide; Pegfilgrastim
Intervention description: Patients will receive 4 cycles of neoadjuvant eribulin followed by 4 cycles of dose-dense doxorubicin and cyclophosphamide (AC).; Neoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide; Neoadjuvant eribulin followed by dose-dense doxorubicin and cyclophosphamide; Growth factor support (pegfilgrastim) can be given at the discretion of the investigator. Administration of pegfilgrastim is required 24 to 48 hours following administration of dose-dense doxorubicin and cyclophosphamide.
Intervention MeSH terms: Cyclophosphamide; Doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast Neoplasms; Breast Cancer; Breast Tumors; Cancer of the Breast; Neoplasms, Breast; Tumors, Breast

Summary:

      Previous studies have shown that chemotherapy has the same effect on treating breast cancer
      whether you receive it before or after surgery. Receiving chemotherapy before surgery, rather
      than after surgery, may allow the patient to have less extensive surgery. The purpose of this
      study is to identify new treatment regimens with better response rates and to find out if the
      combination of eribulin followed by doxorubicin and cyclophosphamide can shrink the size of
      the patient's breast tumor and allow you to preserve your breast. Additionally, by receiving
      chemotherapy before surgery, the investigators will be able to determine if your cancer is
      responsive to chemotherapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically or cytologically confirmed invasive breast carcinoma.

          -  Locally advanced breast cancer (Stage IIIA to IIIC).

          -  Invasive breast cancer must be Her2-negative. If breast cancer is Her2 2+ by
             immunohistochemistry (IHC), then fluorescence in situ hybridization (FISH) must be
             negative for Her2 gene amplification.

          -  No evidence of disease outside the breast or chest wall, except ipsilateral axillary
             lymph nodes on staging scans (CT chest/abdomen/pelvis and bone scan or positron
             emission tomography [PET] scan).

          -  Patients must have measurable disease as defined by palpable lesion with both
             diameters ≥ 1 cm measurable with caliper and/or a positive mammogram or ultrasound
             with at least one dimension ≥ 1 cm. Bilateral mammogram and clip placement is required
             for study entry. Baseline measurements of the indicator lesions must be recorded on
             the Patient Registration Form. To be valid for baseline, the measurements must have
             been made within the 14 days if palpable. If not palpable, a mammogram or MRI must be
             done within 14 days. If palpable, a mammogram or MRI must be done within 2 months
             prior to study entry. If clinically indicated, xrays and scans must be done within 28
             days of study entry.

          -  Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 within 14 days of
             study entry.

          -  Normal (greater than 50%) left ventricular ejection fraction (LVEF) by multigated
             acquisition (MUGA) scan or echocardiography.

          -  Signed informed consent.

          -  Adequate organ function within 2 weeks of study entry:

               -  Absolute neutrophil count ≥ 1500/mm³, Hgb ≥ 9.0 g/dl and platelet count ≥
                  100,000/mm³.

               -  Total bilirubin ≤ upper limit of normal.

               -  Creatinine ≤ 1.5 mg/dL or calculated creatinine clearance rate (CrCL) ≥ 50 mL/min
                  using the Cockroft Gault equation.

               -  Serum glutamate oxaloacetate transaminase (SGOT)/(AST) or serum glutamate
                  pyruvate transaminase (SGPT)/(ALT) and alkaline phosphatase (alk phos) must be
                  within the range allowing for eligibility.

          -  Patients must be over 18 years old.

          -  International normalized ratio (INR) < 1.5 or a prothrombin time (PT)/partial
             thromboplastin time (PTT) within normal limits. Patients receiving anti-coagulation
             treatment with an agent such as warfarin or heparin may be allowed to participate.

          -  Women of childbearing potential must have a negative serum pregnancy test performed
             within 7 days prior to the start of treatment.

          -  Women of childbearing potential and men must agree to use adequate contraception
             (barrier method of birth control) prior to study entry and for the duration of study
             participation.

          -  Patient must have signed informed consent prior to registration on this study.

        Exclusion Criteria:

          -  Prior chemotherapy, hormonal therapy, biologic therapy, investigational agent,
             targeted therapy or radiation therapy for current breast cancer. Patients with history
             of breast cancer greater than 5 years from initial diagnosis are eligible for the
             study. Patients may not have received anthracycline-based chemotherapy in the past.
             Patients with history of ductal carcinoma in situ (DCIS) are eligible if there were
             treated with surgery alone.

          -  Medical, psychological or surgical condition which the investigator feels might
             compromise study participation.

          -  History of previous or current malignancy at other sites with the exception of
             adequately treated carcinoma in-situ of the cervix or basal or squamous cell carcinoma
             of the skin. Patients with a history of other malignancies, who remain disease free
             for greater than five years are eligible.

          -  Evidence of sensory and/or peripheral neuropathy > grade 1.

          -  Serious, uncontrolled, concurrent infection(s).

          -  Major surgery within 4 weeks of the start of study treatment, without complete
             recovery.

          -  Pregnant or lactating women are not eligible. Women of childbearing potential must
             have a negative serum or urine pregnancy test completed within 7 days of study
             treatment. Women or men of childbearing potential not using a reliable and appropriate
             contraceptive method are not eligible. (Postmenopausal woman must have been
             amenorrheic for at least 12 months to be considered of non-childbearing potential).

          -  Known human immunodeficiency virus (HIV) infection or chronic Hepatitis B or C.

          -  Active clinically serious infection > CTCAE Grade 2.

          -  Thromboembolic events such as a cerebrovascular accident including transient ischemic
             attacks within the past 6 months.

          -  Pulmonary hemorrhage/bleeding event ≥ CTCAE Grade 2 within 4 weeks of first dose of
             study drug.

          -  Any other hemorrhage/bleeding event ≥ CTCAE Grade 3 within 4 weeks of first dose of
             study drug.

          -  Cardiac disease: congestive heart failure > class II New York Heart Association
             (NYHA). Patients must not have unstable angina (anginal symptoms at rest) or new onset
             angina (began within the last 3 months) or myocardial infarction within the past 6
             months.

          -  Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI
             of the brain to exclude brain metastasis.

          -  Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy.

          -  Uncontrolled hypertension defined as systolic blood pressure > 150 mmHg or diastolic
             pressure > 90 mmHg, despite optimal medical management.