Clinical Trials /

Eribulin Mesylate and Everolimus in Treating Patients With Triple-Negative Metastatic Breast Cancer

NCT02120469

Description:

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">Eribulin Mesylate</span> and <span class="go-doc-concept go-doc-intervention">Everolimus</span> in Treating Patients With Triple-Negative Metastatic <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: Eribulin Mesylate and Everolimus in Treating Patients With Triple-Negative Metastatic Breast Cancer
  • Official Title: Phase I/IB Trial of Eribulin and Everolimus in Patients With Triple Negative Metastatic Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02120469

    ORG ID: 14036

    NCI ID: NCI-2014-00844

    Trial Conditions

    Estrogen Receptor Negative

    HER2/Neu Negative

    Progesterone Receptor-negative

    Stage IV Breast Cancer

    Triple-negative Breast Carcinoma

    Breast Adenocarcinoma

    Trial Interventions

    Drug Synonyms Arms
    everolimus 42-O-(2-hydroxy)ethyl rapamycin, Afinitor, RAD001 Treatment (everolimus, eribulin mesylate)
    eribulin mesylate B1939, E7389, ER-086526, halichrondrin B analog Treatment (everolimus, eribulin mesylate)

    Trial Purpose

    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.

    Detailed Description

    PRIMARY OBJECTIVES:

    I. To determine the safety and tolerability of everolimus and eribulin (eribulin mesylate),
    and determine the recommended Phase IB dose (RP2D) of the drug combination in patients with
    resistant metastatic triple negative breast cancer (TNBC). (Phase I) II. To evaluate the
    event-free survival (EFS) rate for patients with resistant metastatic TNBC at the RP2D of
    everolimus and eribulin to determine if the drug combination is worthy of further study.
    (Phase IB)

    SECONDARY OBJECTIVES:

    I. To determine response rate in patients with resistant metastatic TNBC. (Phase IB) II. To
    determine overall survival (OS) in patients with resistant metastatic TNBC. (Phase IB) III.
    To determine toxicity in patients with resistant metastatic TNBC. (Phase IB) IV. To
    determine pharmacokinetics (PK) for everolimus and eribulin in patients with resistant
    metastatic TNBC. (Phase IB) V. To collect blood, skin punch biopsies, and tumor biopsies
    before and after treatment from all patients and perform proteomic analysis to determine the
    level of inhibition of the phosphatidylinositol 3 kinase (PI3K) pathway in tumor cells
    versus non-therapeutic targets. (Phase IB)

    OUTLINE: This is a dose-escalation study of everolimus.

    Patients receive everolimus orally (PO) once daily (QD) on days 1-21 and eribulin mesylate
    intravenously (IV) on days 1 and 8. Courses repeat every 21 days in the absence of disease
    progression or unacceptable toxicity.

    After completion of study treatment, patients are followed up periodically.

    Trial Arms

    Name Type Description Interventions
    Treatment (everolimus, eribulin mesylate) Experimental Patients receive everolimus PO QD on days 1-21 and eribulin mesylate IV on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. everolimus, eribulin mesylate

    Eligibility Criteria

    Inclusion Criteria:

    - Patients with histologically-confirmed stage IV adenocarcinoma TNBC

    - Patients must have had prior treatment with anthracyclines and/or taxanes (resistant)
    including adjuvant or neoadjuvant therapy

    - Patients with measurable disease per Response Evaluation Criteria in Solid Tumors
    (RECIST) 1.1, defined as at least one lesion that can be accurately measured in at
    least one dimension (longest diameter to be recorded) as > 20 mm with conventional
    techniques or as > 10 mm with spiral computed tomography (CT) scan; for patients with
    bone only metastases, there must be at least one measurable predominant lytic bone
    lesion

    - Patients with chemotherapy for metastatic disease (patients with 0-4 prior lines of
    chemotherapy for metastatic breast cancer [MBC]); this includes prior everolimus
    therapy

    - 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

    - Total bilirubin less =< to 1 times upper limit of normal (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

    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

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Recommended Phase 2 Dose (RP2D) of the eribulin mesylate and everolimus, determined according to the NCI CTCAE v4.0 (Phase I)

    Event-free survival using the Response Evaluation Criteria in Solid Tumors (RECIST) (Phase IB)

    Secondary Outcome Measures

    Incidence of adverse events, graded according to the NCI CTCAE v4.0 (Phase IB)

    Response rate using the RECIST (Phase IB)

    Overall survival (Phase IB)

    PK parameters of everolimus in blood samples

    PK parameters of eribulin mesylate in plasma samples

    Progression free survival (Phase Ib)

    Trial Keywords