A Phase 2 Study of Eribulin Followed by AC as Preoperative Therapy for HER2-negative Inflammatory Breast Cancer
Condition: Inflammatory Breast Cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast
MeSH terms: Breast Neoplasms; Inflammatory Breast Neoplasms
Intervention: Eribulin; Adriamycin; Cyclophosphamide
Intervention description: administered IV for 4 cycles; administered IV with cyclophosphamide for 4 cycles; administered IV with adriamycin for 4 cycles
Intervention MeSH terms: Cyclophosphamide; Doxorubicin; Liposomal doxorubicin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: inflammatory breast cancer; Human Epidermal Growth Factor 2 Negative Carcinoma of Breast

Summary:

      This research study is studying a drug called eribulin combined with standard treatment as a
      possible preoperative treatment for HER2 negative inflammatory breast cancer.
    

Eligibility criteria:

        Inclusion Criteria:

        -Participants must have histologically confirmed invasive breast cancer. All histologic
        subtypes are eligible.

        -- Patients must NOT have HER2 positive status based on ASCO/CAP guidelines defined as: IHC
        3+ based on circumferential membrane staining that is complete, intense and/or

        FISH positive based on one of the three following criteria:

        Single-probe average HER2 copy number ≥ 6.0 signals/cell; OR Dual-probe HER2/CEP17 ratio
        <2.0 with an average HER2 copy number ≥ 6.0 signals/cell; OR Dual-probe HER2/CEP17 ratio
        ≥2.0

          -  Age ≥18 years. Because no dosing or adverse event data are currently available on the
             use of eribulin in participants <18 years of age, children are excluded from this
             study

          -  ECOG performance status ≤1 (Karnofsky ≥70%)

          -  Participants must have normal organ and marrow function as defined below:

               -  leukocytes ≥3,000/mcL

               -  absolute neutrophil count ≥1,500/mcL

               -  platelets ≥100,000/mcL

               -  total bilirubin within normal institutional limits

               -  AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal creatinine ≤1.5 ×
                  institutional upper limit of normal

                  --- OR

               -  creatinine clearance ≥60 mL/min/1.73 m2 for participants with creatinine levels
                  above institutional normal.

          -  Patients must have the clinical diagnosis of inflammatory breast cancer.

          -  Patients must be without evidence of visceral or bone involvement with metastatic
             cancer on physical exam or any diagnostic study. Extensive nodal involvement (distant
             or regional) is allowed.

          -  LVEF > 50% calculated by echocardiogram (ECHO)

          -  Patients may have bilateral breast cancer so long as one breast meets criteria for
             inflammatory breast cancer, and the breast with inflammatory breast cancer has never
             received prior therapy.

          -  The effects of eribulin on the developing human fetus are unknown. For this reason and
             because other therapeutic agents used in this trial are known to be teratogenic, women
             of child-bearing potential and men must agree to use adequate contraception (hormonal
             or barrier method of birth control; abstinence) prior to study entry and for the
             duration of study participation. Should a woman become pregnant or suspect she is
             pregnant while she or her partner is participating in this study, she should inform
             her treating physician immediately. Men treated or enrolled on this protocol must also
             agree to use adequate contraception prior to the study, for the duration of study
             participation, and 4 months after completion of chemotherapy administration.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Both men and women of all races and ethnic groups are eligible for this trial. Because
             breast cancer predominantly affects females, it is anticipated that male enrollment
             will be < 5% of the overall study population.

        Exclusion Criteria:

          -  Participants who are receiving any other investigational agents.

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to eribulin or other agents used in study.

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements.

          -  Pregnant women are excluded from this study because eribulin is an agent with the
             potential for teratogenic or abortifacient effects. Because there is an unknown but
             potential risk for adverse events in nursing infants secondary to treatment of the
             mother with eribulin, breastfeeding should be discontinued if the mother is treated
             with eribulin. These potential risks may also apply to other agents used in this
             study.

          -  HIV-positive participants on combination antiretroviral therapy are ineligible because
             of the potential for pharmacokinetic interactions with eribulin. In addition, these
             participants are at increased risk of lethal infections when treated with
             marrow-suppressive therapy. Appropriate studies will be undertaken in participants
             receiving combination antiretroviral therapy when indicated.

          -  A baseline corrected QT interval of > 470 ms.

          -  Individuals with a history of a different malignancy are ineligible except for the
             following circumstances. Individuals with a history of other malignancies are eligible
             if they have been disease-free for at least 3 years and are deemed by the investigator
             to be at low risk for recurrence of that malignancy. Individuals with the following
             cancers are eligible if diagnosed and treated within the past 3 years: cervical cancer
             in situ, and basal cell or squamous cell carcinoma of the skin.

          -  Patients may not have received eribulin, paclitaxel, doxorubicin, or cyclophosphamide
             as anti-neoplastic therapy.