Clinical Trials /

A Phase 2 Study of Eribulin Followed by AC as Preoperative Therapy for HER2-negative Inflammatory Breast Cancer

NCT02623972

Description:

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

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

A Phase 2 Study of Eribulin Followed by AC as Preoperative Therapy for <span class="go-doc-concept go-doc-biomarker">HER2</span>-negative <span class="go-doc-concept go-doc-disease">Inflammatory Breast Cancer</span>

Title

  • Brief Title: A Phase 2 Study of Eribulin Followed by AC as Preoperative Therapy for HER2-negative Inflammatory Breast Cancer
  • Official Title: A Phase 2 Study of Eribulin Followed by Doxorubicin and Cyclophosphamide as Preoperative Therapy for HER2-negative Inflammatory Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02623972

    ORG ID: 15-292

    Trial Conditions

    Inflammatory Breast Cancer

    Human Epidermal Growth Factor 2 Negative Carcinoma of Breast

    Trial Interventions

    Drug Synonyms Arms
    Eribulin Halaven, B1939 mesylate Eribulin
    Adriamycin Doxorubicin Eribulin
    Cyclophosphamide Cytoxan, Neosar Eribulin

    Trial Purpose

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

    Detailed Description

    This research study is a Phase II clinical trial. Phase II clinical trials test the safety
    and effectiveness of an investigational intervention to learn whether the intervention works
    in treating a specific disease. "Investigational" means that the intervention is being
    studied..

    Eribulin works by interfering with cancer cell division, growth, and spread.

    The goal of this research study is to evaluate inflammatory breast cancer's response to
    treatment with eribulin followed by AC chemotherapy when given as a preoperative
    chemotherapy treatment for participants with HER2 negative inflammatory breast cancer.

    Trial Arms

    Name Type Description Interventions
    Eribulin Experimental Eribulin-Administered via iv, at predetermined dosage and schedule per cycle Two research breast biopsies Adriamycin (doxorubicin) via iv a predetermined dosage and schedule per cycle Cyclophosphamide (AC) via iv a predetermined dosage and schedule per cycle Surgical Removal of the breasts (Mastectomy) and axillary lymph node dissection Radiation Therapy Endocrine Therapy (if applicable) Optional 10 Patient-Optional DCE-MRI (Dynamic Contrast Enhanced-Magnetic Resonance Imaging) scans Eribulin, Adriamycin, Cyclophosphamide

    Eligibility Criteria

    Inclusion Criteria:

    - Participants must have histologically confirmed invasive breast cancer. All
    histologic subtypes are eligible.

    -- Patients must have known HER2 status defined as negative (defined as IHC 0 or 1+,
    or FISH ratio <2.0). Any ER or PR status is allowed.

    - 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%, see Appendix A)

    - 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 within
    normal institutional limits

    --- 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 as evidenced
    by the onset of signs and symptoms noted below within a 6 month time-period:

    - Erythema of the breast

    - Edema of the skin of the breast

    - Enlargement of the breast

    - Patients must be without evidence of visceral or bone involvement with metastatic
    cancer on physical exam or any diagnostic study. Extensive nodal involvement 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 neither breast cancer has 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 eribulin 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.

    - Participants with known brain metastases should be excluded from this clinical trial
    because of their poor prognosis and because they often develop progressive neurologic
    dysfunction that would confound the evaluation of neurologic and other adverse
    events.

    - Patients with evidence of metastatic disease involvement in viscera or bone.

    - 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 paclitaxel, doxorubicin, or cyclophosphamide as
    anti-neoplastic therapy.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Pathologic Complete Response

    Secondary Outcome Measures

    Disease Free Survival

    Time to Treatment Failure

    Overall Survival

    Pathologic disease response at mastectomy will be reported as "residual disease burden (RCB)".

    RT-qPCR assessment of gene expression of 10-EMT-related genes and 15-genes involved in modulating vessel phenotype or EC-PVC interactions will be compared following treatment with eribulin.

    To correlate changes in imaging (Ktrans ve, vp, and initial area under the curve (iAUC)) with genomic changes determined on core biopsies of the breast sampled at the same time points.

    Trial Keywords

    inflammatory breast cancer

    Human Epidermal Growth Factor 2 Negative Carcinoma of Breast