Clinical Trials /

A Study of Abemaciclib (LY2835219) in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer

NCT02675231

Description:

The purpose of this study is to evaluate the effectiveness of abemaciclib plus trastuzumab with or without fulvestrant or chemotherapy in women with hormone receptor positive (HR+), human epidermal growth factor receptor 2 positive (HER2+) locally advanced or metastatic breast cancer after prior exposure to at least two HER2-directed therapies for advanced disease.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

A Study of <span class="go-doc-concept go-doc-intervention">Abemaciclib</span> (LY2835219) in Women With HR+, <span class="go-doc-concept go-doc-biomarker">HER2</span>+ Locally Advanced or <span class="go-doc-concept go-doc-disease">Metastatic Breast Cancer</span>

Title

  • Brief Title: A Study of Abemaciclib (LY2835219) in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer
  • Official Title: monarcHER: A Phase 2, Randomized, Multicenter, 3-Arm, Open-Label Study to Compare the Efficacy of Abemaciclib Plus Trastuzumab With or Without Fulvestrant to Standard-of-Care Chemotherapy of Physician's Choice Plus Trastuzumab in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02675231

    ORG ID: 15804

    NCI ID: I3Y-MC-JPBZ

    Trial Conditions

    Hormone Receptor Positive Tumor

    HER-2 Positive Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Abemaciclib LY2835219 Abemaciclib + Trastuzumab + Fulvestrant, Abemaciclib + Trastuzumab
    Trastuzumab Abemaciclib + Trastuzumab + Fulvestrant, Abemaciclib + Trastuzumab, Trastuzumab + Standard of Care Chemotherapy
    Fulvestrant Abemaciclib + Trastuzumab + Fulvestrant
    Standard of Care Single Agent Chemotherapy Trastuzumab + Standard of Care Chemotherapy

    Trial Purpose

    The purpose of this study is to evaluate the effectiveness of abemaciclib plus trastuzumab
    with or without fulvestrant or chemotherapy in women with hormone receptor positive (HR+),
    human epidermal growth factor receptor 2 positive (HER2+) locally advanced or metastatic
    breast cancer after prior exposure to at least two HER2-directed therapies for advanced
    disease.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Abemaciclib + Trastuzumab + Fulvestrant Experimental Abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a maintenance dose IV infusion on Day 1 of each subsequent cycle; plus fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter. Abemaciclib, Trastuzumab, Fulvestrant
    Abemaciclib + Trastuzumab Experimental Abemaciclib given orally Q12H of a 21-day cycle; plus trastuzumab IV infusion on Day 1 of the cycle then a maintenance dose IV infusion on Day 1 of each subsequent cycle. Abemaciclib, Trastuzumab
    Trastuzumab + Standard of Care Chemotherapy Active Comparator Trastuzumab IV infusion on Day 1 of a 21-day cycle then a maintenance dose IV infusion on Day 1 of each subsequent cycle plus standard of care single agent chemotherapy of physician's choice administered according to product label. Trastuzumab, Standard of Care Single Agent Chemotherapy

    Eligibility Criteria

    Inclusion Criteria:

    - diagnosis of HR+, HER2+ breast cancer (BC)

    - unresectable locally advanced recurrent BC or metastatic BC

    - adequate tumor tissue available and collected prior to randomization

    - measurable and/or non-measurable disease according to Response Evaluation Criteria in
    Solid Tumors (RECIST) version 1.1

    - previously received:

    - at least 2 HER2-directed therapies for advanced disease

    - participant must have received trastuzumab emtansine (T-DM1) in any disease
    setting

    - must have received a taxane in any disease setting

    - may have received any endocrine therapy (excluding fulvestrant)

    - have postmenopausal status

    - performance status (PS) of 0 to 1 on the Eastern Cooperative Oncology Group scale

    - left ventricular ejection fraction (LVEF) of 50% or higher at baseline

    - adequate organ function

    - negative serum pregnancy test at baseline (within 14 days prior to randomization) and
    agree to use medically approved precautions to prevent pregnancy during the study and
    for 12 weeks following the last dose of abemaciclib id menopause induced by
    gonadotropin-releasing hormone (GnRH) agonist or radiation

    - discontinued previous localized radiotherapy for palliative purposes or for lytic
    lesions at risk of fracture at least 2 weeks prior to randomization and recovered
    from the acute effects of therapy

    - discontinued all previous therapies for cancer (including chemotherapy, radiotherapy,
    immunotherapy, and endocrine therapy), except trastuzumab, for at least 21 days for
    myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving
    study drug, and recovered from the acute effects of therapy

    Exclusion Criteria:

    - have visceral crisis

    - known central nervous system (CNS) metastases that are untreated, symptomatic, or
    require steroids to control symptoms

    - had major surgery within 14 days prior to randomization

    - received prior treatment with any cyclin-dependent kinase (CDK) 4 and CDK 6 inhibitor

    - received treatment with a drug that has not received regulatory approval for any
    indication within 14 or 21 days of randomization for a nonmyelosuppressive or
    myelosuppressive agent, respectively

    - have serious preexisting medical conditions that, in the judgment of the
    investigator, would preclude participation in this study

    - history within the last 6 months of symptomatic congestive heart failure, myocardial
    infarction, or unstable angina

    - history within the last 12 months of any of the following conditions: syncope of
    cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden
    cardiac arrest

    - history of any other cancer (except non-melanoma skin cancer or carcinoma in-situ of
    the cervix), unless in complete remission with no therapy for a minimum of 3 years

    - active bacterial, fungal infection, or detectable viral infection

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Progression Free Survival (PFS)

    Secondary Outcome Measures

    Overall Survival (OS)

    Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR)

    Duration of Response (DoR)

    Percentage of Participants with a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR)

    Proportion of Participants with Best Overall Response of CR, PR, or SD with Duration of SD for at Least 6 Months: Clinical Benefit Rate (CBR)

    Change from Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf)

    Change from Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30)

    Change from Baseline in Health Status on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L)

    Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and its Metabolites, Fulvestrant, and Trastuzumab

    Trial Keywords