Eribulin Mesylate and Everolimus in Treating Patients With Triple-Negative Metastatic Breast Cancer
Condition: Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor-negative; Stage IV Breast Cancer; Triple-negative Breast Carcinoma
MeSH terms: Breast Neoplasms
Intervention: everolimus; eribulin mesylate; pharmacological study; laboratory biomarker analysis
Intervention description: Given PO; Given IV; Correlative studies; Optional correlative studies
Intervention MeSH terms: Everolimus
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase I/IB trial studies the side effects and best dose of eribulin mesylate and
      everolimus in treating patients with breast cancer that does not have estrogen receptors,
      progesterone receptors, or large amounts of human epidermal growth factor receptor 2 protein
      (triple-negative) and has spread to other places in the body (metastatic). Eribulin mesylate
      and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for
      cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have histologically-confirmed stage IV TNBC (patients who had metastatic
             disease within 6 months of lumpectomy or mastectomy for treatment of TNBC may be
             excused from repeat biopsy)

          -  Be willing to provide tissue from a newly obtained core or excisional biopsy of a
             tumor lesion; newly obtained is defined as a specimen obtained up to 6 weeks (42 days)
             prior to initiation of treatment on day 1; subjects for whom newly obtained samples
             cannot be provide (e.g. inaccessible or subject safety concern) may submit an archived
             specimen only upon agreement from the study principle investigator (PI)

          -  Patients must have had prior treatment with anthracyclines and/or taxanes (resistant)
             or platinum including adjuvant or neoadjuvant therapy

          -  Both measurable as well as non-measurable disease per Response Evaluation Criteria in
             Solid Tumors (RECIST) version 1.1, will be allowed

          -  Patients with chemotherapy for metastatic disease (patients with 0-3 prior lines of
             chemotherapy for metastatic breast cancer [MBC])

          -  Life expectancy of >= 3 months

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2

          -  Hemoglobin >= 9.0 g/dl

          -  Absolute neutrophil count (ANC) >= 1,500/mm^3

          -  Platelet count >= 100,000/mm^3

          -  Creatinine =< 1.5 times the upper limit of normal (ULN)

          -  Total bilirubin less =< to 1 times ULN

          -  Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< to 2.5 times
             the ULN if no liver metastases; for patients with known liver metastases, AST and ALT
             must be =< to 5 times the ULN

          -  Women of child-bearing potential must agree to use adequate contraception (hormonal or
             barrier method of birth control or abstinence) prior to study entry and for up to 8
             weeks after ending treatment; should a woman become pregnant or suspect that she is
             pregnant while participating on the trial, she should inform her treating physician
             immediately

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Be willing to use dexamethasone mouthwash as directed

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering
             the study or those who have not recovered from adverse events (AEs) due to agents
             administered > 3 weeks prior to entering the study

          -  Patients may not be receiving any other investigational agents

          -  Patients with symptomatic brain metastases are excluded from this clinical trial

          -  Uncontrolled current illness including, but not limited to, ongoing or active
             infection (> grade 2 based on the National Cancer Institute Common Terminology
             Criteria for Adverse Events [NCI CTCAE] version [v]4.0), symptomatic congestive heart
             failure, unstable angina pectoris, myocardial infarction within the past 6 months,
             cardiac ventricular arrhythmias requiring anti-arrhythmic therapy, or psychiatric
             illness/social situations that would limit compliance with study requirements

          -  Pregnant women

          -  Prior eribulin use

          -  Patients with human immunodeficiency virus (HIV), chronic hepatitis B, or chronic
             hepatitis C (known from the existing medical record)

          -  Concomitant use with strong or moderate cytochrome P450, family 3, subfamily A,
             polypeptide 4 (CYP3A4)/P-glycoprotein (PgP) inhibitors and CYP3A4/PgP inducers

          -  Women of child-bearing potential (WOCBP), defined as all women physiologically capable
             of becoming pregnant, must use highly effective methods of contraception during the
             study and 8 weeks after ending treatment; highly effective contraception methods
             include combination of any two of the following:

               -  Use of oral, injected or implanted hormonal methods of contraception or

               -  Placement of an intrauterine device (IUD) or intrauterine system (IUS)

               -  Barrier methods of contraception: condom or occlusive cap (diaphragm or
                  cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository

               -  Total abstinence

               -  Male/female sterilization

        Women are considered post-menopausal and not of child-bearing potential if they have had 12
        months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age
        appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy
        (with or without hysterectomy) or tubal ligation at least six weeks prior to randomization;
        in the case of oophorectomy alone, only when the reproductive status of the woman has been
        confirmed by follow up hormone level assessment is she considered not of child-bearing
        potential

          -  Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate
             contraception, during the study and for 8 weeks after the end of treatment

          -  Noncompliant with oral medication and/or dexamethasone mouth wash