Clinical Trials /

Eribulin Mesylate or Paclitaxel as First- or Second-Line Therapy in Treating Patients With Recurrent Stage IIIC-IV Breast Cancer

NCT02037529

Description:

This randomized phase III trial studies how well eribulin mesylate or paclitaxel work as first- or second-line therapy in treating patients with stage IIIC-IV breast cancer that has come back. Drugs used in chemotherapy, such as eribulin mesylate and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Suspended

Phase:

Phase 3

Trial Eligibility

Document

A Randomized Phase III Trial of <span class="go-doc-concept go-doc-intervention">Eribulin</span> Compared to Standard Weekly <span class="go-doc-concept go-doc-intervention">Paclitaxel</span> as First- or Second-Line Therapy for Locally Recurrent or Metastatic <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: A Randomized Phase III Trial of Eribulin Compared to Standard Weekly Paclitaxel as First- or Second-Line Therapy for Locally Recurrent or Metastatic Breast Cancer
  • Official Title:
  • Clinical Trial IDs

    NCT ID: NCT02037529

    ORG ID: E7389-A001-303

    NCI ID: RU011201I

    Trial Conditions

    Metastatic Breast Cancer

    Locally Recurrent Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Eribulin A
    Paclitaxel B

    Trial Purpose

    This is a two arm Phase III trial in first and second-line HER2 negative patients with
    locally recurrent or metastatic breast cancer. The primary endpoint is overall survival
    (OS), and the objective is to test for the superiority of eribulin mesylate over standard
    weekly paclitaxel. Patients will be randomized between the experimental and control arm with
    equal allocation (1:1) within strata defined by prior adjuvant taxanes, hormone receptor
    status, and line of therapy. Subjects will continue protocol directed therapy until
    documentation of disease progression, development of unacceptable toxicity, or withdrawal of
    consent. Those who discontinue study treatment without radiological progression will be
    followed with repeat imaging studies every 12 weeks. All subjects will be followed until
    death, withdrawal of consent, or study termination.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    A Experimental Eribulin on Days 1 and 8 of each cycle (cycle length: 21 days) Eribulin
    B Active Comparator Paclitaxel on Days 1, 8, and 15 of each cycle (cycle length: 28 days) Paclitaxel

    Eligibility Criteria

    Inclusion Criteria:

    1. Histologic confirmation of invasive adenocarcinoma originating in the breast.

    2. Stage IV disease or Stage IIIC disease (using the 7th edition AJCC criteria) not
    amenable to local therapy.

    3. Radiographically measurable disease as per RECIST guidelines (version 1.1).

    4. Radiographic evidence of disease progression.

    5. Documentation of HER2 negative breast cancer at the time of protocol registration.

    6. Known hormone receptor status at the time of protocol registration.

    7. Prior systemic therapy as per the following criteria:

    1. Patients must demonstrate resolution of all prior chemotherapy or
    radiation-related toxicities to grade less than or equal to 1, including
    peripheral neuropathy, with the exception of alopecia (any grade permissible).

    2. No more than one prior chemotherapy regimen for advanced or metastatic breast
    cancer is allowed. Prior chemotherapy for metastatic disease must have been
    completed greater than or equal to 14 days prior to randomization.

    3. Prior treatment may include a taxane in the adjuvant or neoadjuvant setting,
    provided that the interval between the completion of adjuvant therapy and
    disease recurrence is greater than 12 months.

    4. Any number of prior hormonal therapies is allowed.

    5. Any number of biologic therapies (e.g., bevacizumab) or immunotherapies is
    allowed in the absence of co-administered chemotherapy and must have been
    completed greater than or equal to 28 days prior to randomization.

    6. Prior treatment with an investigational agent is allowed but must have been
    completed greater than or equal to 28 days prior to randomization.

    8. Prior local therapy as per the following criteria:

    1. Minor surgical procedures must be completed greater than or equal to 7 days
    prior to randomization with documentation of adequate recovery from associated
    complications to grade less than or equal to 1.

    2. Major surgical procedures and open biopsies must be completed greater than or
    equal to 28 days prior to randomization with documentation of adequate recovery
    from associated complications to grade less than or equal to 1.

    3. Prior radiotherapy must be completed greater than or equal to 14 days prior to
    randomization with documentation of adequate recovery from associated toxicities
    to grade less than or equal to 1.

    9. Concurrent supportive therapy as per the following criteria:

    1. Treatment with bisphosphonates or denosumab is allowed and recommended per the
    standard of care.

    2. Therapeutic anticoagulation is allowed for patients on a stable dose of warfarin
    or low molecular weight heparin.

    10. ECOG performance status of 0, 1, or 2.

    11. Life expectancy of greater than 12 weeks.

    12. History of brain metastases as per the following criteria:

    1. Patients with a history of resected brain metastases are eligible only if they
    are asymptomatic and have stable MRI scans for 3 consecutive months, including
    less than or equal to 28 days of study registration.

    2. Patients who receive stereotactic radiosurgery or whole brain radiation for
    brain metastases are eligible only if they are asymptomatic and have stable MRI
    scans for 3 consecutive months, including less than or equal to 28 days of study
    registration.

    13. Adequate organ function per blood work obtained less than 7 days prior to
    registration.

    1. Absolute neutrophil count greater than or equal to 1500/uL.

    2. Platelet count greater than or equal to 100,000/uL.

    3. Hemoglobin greater than or equal to 9 g/dL.

    4. Total bilirubin less than or equal to 1.5 times the upper limit of normal (ULN)
    except for unconjugated hyperbilirubinemia of Gilbert's syndrome.

    5. SGOT (AST) and SGPT (ALT) less than or equal to 3 x ULN except in the case of
    liver metastases, where less than or equal to 5 x ULN is allowed.

    6. Creatinine less than or equal to 2.0 mg/dL or creatinine clearance greater than
    50 mL/min.

    7. QTc interval less than or equal to 500 msec on the baseline electrocardiogram.

    8. Negative pregnancy test done less than or equal to 72 hours prior to
    registration for women of childbearing potential only.

    14. Ability to complete questionnaire(s) independently or with assistance.

    15. Willingness to provide blood and tissue samples for correlative research purposes.

    16. Ability to comprehend and respond to questions using a telephone keypad.

    Exclusion Criteria:

    1. Prior malignancy, other than carcinoma in situ of the cervix and non-melanoma skin
    cancers, unless the prior malignancy was diagnosed and definitively treated greater
    than or equal to 5 years previously, there is no subsequent evidence of recurrence,
    and the patient is considered by a physician to be at less than 30% risk of relapse.

    2. Any of the following because this study involves an investigational agent whose
    genotoxic, mutagenic, and teratogenic effects on the developing fetus and newborn are
    unknown:

    1. Pregnant women

    2. Nursing women

    3. Men or women of childbearing potential who are unwilling to employ adequate
    contraception

    3. Presence of a serious nonhealing wound, ulcer, or bone fracture.

    4. History of CTCAE grade greater than or equal to 3 hypersensitivity to paclitaxel or
    Cremophor EL.

    5. Pre-existing peripheral neuropathy grade greater than or equal to 2 at registration.

    6. Significant cardiovascular impairment (e.g., New York Heart Association congestive
    heart failure of grade II or above, unstable angina, myocardial infarction within the
    past 6 months, or serious cardiac arrhythmia).

    7. Subjects with known positive HIV status.

    8. History of stroke or transient ischemic attack less than or equal to 6 months prior
    to registration.

    9. History of uncontrolled seizures.

    10. Severe or uncontrolled intercurrent illness/infection.

    11. Concurrent administration of any other investigational agent considered to have
    potential efficacy in the treatment of breast cancer.

    12. Prior exposure to eribulin mesylate.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    Overall Survival (OS) of subjects from Baseline taking eribulin mesylate vs. subjects taking paclitaxel

    Secondary Outcome Measures

    Objective tumor response as defined by RECIST 1.1

    Duration of tumor response

    Time-to-treatment-failure of eribulin mesylate

    Treatment-related toxicity of eribulin mesylate

    Progression-Free Survival (PFS) defined as the time from randomization to progression (under RECIST 1.1 criteria) or death due to any cause, whichever occurs first

    Trial Keywords

    Breast Cancer

    Metastatic

    Locally Recurrent