Neoadjuvant Study of Sequential Eribulin Followed by FAC Compared to Sequential Paclitaxel Followed by FEC in Early Stage Breast Cancer Not Overexpressing HER-2
Condition: Breast Cancer
MeSH terms: Breast Neoplasms
Intervention: Paclitaxel; Eribulin; 5-Fluorouracil; Epirubicin; Cyclophosphamide; Doxorubicin
Intervention description: 80 mg/m2 by vein over 1 hour on Days 1, 8, and 15 of each 21-day cycle.; 1.4 mg/m2 by vein over 2-5 minutes on Days 1 and 8 of each 21-day study cycle.; 500 mg/m2 by vein on day 1 for 4 cycles (21 day cycle) at preference of treating physicians.; 100 mg/m2 by vein on day 1 for 4 cycles (21 day cycle) at preference of treating physicians.; 500 mg/m2 by vein on day 1 for 4 cycles (21 day cycle) at preference of treating physicians.; 50 mg/m2 by vein on day 1, over 72 hour continuous infusion or intravenous bolus, for 4 cycles (21 day cycle) at preference of treating physicians.
Intervention MeSH terms: Paclitaxel; Cyclophosphamide; Doxorubicin; Liposomal doxorubicin; Fluorouracil; Epirubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Breast cancer; Early Stage Breast Cancer Not Overexpressing HER-2; Primary invasive adenocarcinoma of the breast; Paclitaxel; Taxol; Eribulin; E7389; 5-Fluorouracil; 5-FU; Adrucil; Efudex; Epirubicin; Ellence; Cyclophosphamide; Cytoxan; Neosar; Doxorubicin; Doxorubicin hydrochloride; Adriamycin PFS; Adriamycin RDF; Adriamycin; Rubex

Summary:

      The goal of this clinical research study is to learn if and how well eribulin, given in
      combination with standard chemotherapy, can treat early-stage breast cancer compared to
      paclitaxel given in combination with standard chemotherapy. In this study, the standard
      chemotherapy being given is either 5-fluorouracil, epirubicin, and cyclophosphamide (called
      FEC) or 5-fluorouracil, doxorubicin, and cyclophosphamide (called FAC).

      Eribulin is a changed version of the structure of a natural substance from a sea sponge. It
      is designed to block cells from dividing, which may cause cancer cells to die.

      Paclitaxel is designed to block cancer cells from dividing, which may cause them to die.

      5-fluorouracil is designed to block cancer cells from growing and dividing, which may slow or
      stop their growth and spread throughout the body. This may cause the cancer cells to die.

      Epirubicin is designed to block the way cancer cells grow and divide, which may slow or stop
      their growth and spread throughout the body. This may cause the cancer cells to die.

      Doxorubicin is designed to stop the growth of cancer cells, which may cause the cells to die.

      Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may
      slow or stop their growth and/or keep them from spreading throughout the body. This may cause
      the cancer cells to die.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Signed written informed consent

          2. Histologically confirmed primary invasive adenocarcinoma of the breast.

          3. Clinical stage breast cancer T2-3, N0-3, M0

          4. Negative HER-2/neu expression as determined by local hospital laboratory using
             Fluorescence In Situ Hybridization (FISH), or is less or equal to 1+ using
             Immunohistochemistry (IHC).

          5. No prior treatment for primary invasive adenocarcinoma of the breast such as
             irradiation, chemotherapy, hormonal therapy, immunotherapy, investigational therapy or
             surgery. Subjects receiving hormone replacement treatment (HRT) are eligible if this
             therapy is discontinued at least 2 weeks before starting study treatment. Treatment
             for DCIS is allowed, such as surgery, hormonal therapy and radiotherapy.

          6. Karnofsky performance status (KPS) of 80 - 100

          7. The ability and willingness to comply with scheduled visits, treatment plan,
             laboratory tests, and other study procedures.

          8. Baseline MUGA or echocardiogram scans with LVEF of > 50%.

          9. Normal PTT and either INR or PT < 1.5 x ULN.

         10. Men or women 18 years of age or older.

         11. Women of childbearing potential (WOCBP) must agree to use a medically acceptable
             method of contraception to avoid pregnancy throughout the study and for up to 8 weeks
             after the last dose of study drugs.

         12. Willingness to have core biopsies and/or FNA performed before the start of study
             treatment and at the end of 12 week on treatment.

        Exclusion Criteria:

          1. Women who are pregnant (including positive pregnancy test at enrollment or prior to
             study drug administration) or breast-feeding.

          2. Disease free of prior malignancy for < 5 years with the exception of DCIS, curatively
             treated basal carcinoma of the skin, local skin squamous cell carcinoma, or carcinoma
             in situ of the cervix.

          3. Absolute neutrophils count (ANC) < 1500/mm^3

          4. Total bilirubin > 1.5 times the upper limit of normal (ULN)

          5. AST or ALT > 2.5 times the upper limit of normal (ULN)

          6. Platelets < 100,000/mm^3.

          7. Serum creatinine > 1.5 x ULN or creatinine clearance < 60 mL/min (measured or
             calculated by Cockcroft-Galt method)

          8. Evidence of metastatic breast cancer following a standard tumor staging work-up

          9. Evidence of inflammatory breast cancer.

         10. Evidence of any grade 2 sensory or motor neuropathy.

         11. Known human immunodeficiency viral (HIV) infection

         12. Serious intercurrent infections or non-malignant medical illness that are uncontrolled
             or the control of which may be jeopardized by this therapy.

         13. Psychiatric disorders or other conditions rendering the subject incapable of complying
             with the requirements of the protocols.