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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02675231
Recruitment Status : Active, not recruiting
First Posted : February 5, 2016
Last Update Posted : August 28, 2019
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company

Tracking Information
First Submitted Date  ICMJE February 3, 2016
First Posted Date  ICMJE February 5, 2016
Last Update Posted Date August 28, 2019
Actual Study Start Date  ICMJE May 23, 2016
Actual Primary Completion Date April 8, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 3, 2016)
Progression Free Survival (PFS) [ Time Frame: Baseline to Progressive Disease or Death from Any Cause (Estimated up to 24 Months) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02675231 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2016)
  • Overall Survival (OS) [ Time Frame: Baseline to Death from Any Cause (Estimated up to 48 Months) ]
  • Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Objective Response Rate (ORR) [ Time Frame: Baseline to Objective Disease Progression (Estimated up to 24 Months) ]
  • Duration of Response (DoR) [ Time Frame: Date of CR or PR to Date of Objective Disease Progression or Death from Any Cause (Estimated up to 24 Months) ]
  • Percentage of Participants with a Best Overall Response of CR, PR, or Stable Disease (SD): Disease Control Rate (DCR) [ Time Frame: Baseline to Objective Disease Progression (Estimated up to 24 Months) ]
  • 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) [ Time Frame: Date of CR, PR or SD to 6 Months Post CR, PR or SD (Estimated up to 24 Months) ]
  • Change from Baseline in Pain and Symptom Burden Assessment on the Modified Brief Pain Inventory-Short Form (mBPI-sf) [ Time Frame: Baseline, up to 30 Days After Treatment Discontinuation (Estimated up to 24 Months) ]
  • Change from Baseline in Symptom Burden on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) [ Time Frame: Baseline, up to 30 Days After Treatment Discontinuation (Estimated up to 24 Months) ]
  • Change from Baseline in Health Status on the EuroQol 5-Dimension, 5-Level Questionnaire (EQ-5D-5L) [ Time Frame: Baseline, up to 30 Days After Treatment Discontinuation (Estimated up to 24 Months) ]
  • Pharmacokinetics (PK): Minimum Steady State Concentration (Cmin,ss) of Abemaciclib and its Metabolites, Fulvestrant, and Trastuzumab [ Time Frame: Predose Cycle 1 through Cycle 5 Day 1 (Approximately 4 Months) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Abemaciclib (LY2835219) in Women With HR+, HER2+ Locally Advanced or Metastatic Breast Cancer
Official Title  ICMJE 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
Brief Summary 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 Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hormone Receptor Positive Tumor
  • HER-2 Positive Breast Cancer
Intervention  ICMJE
  • Drug: Abemaciclib
    Administered Orally
    Other Name: LY2835219
  • Drug: Trastuzumab
    Administered IV
  • Drug: Fulvestrant
    Administered IM
  • Drug: Standard of Care Single Agent Chemotherapy
    Standard-of-care single-agent chemotherapy of physician's choice administered according to product label
Study Arms  ICMJE
  • Experimental: Abemaciclib + Trastuzumab + Fulvestrant
    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.
    Interventions:
    • Drug: Abemaciclib
    • Drug: Trastuzumab
    • Drug: Fulvestrant
  • Experimental: Abemaciclib + Trastuzumab
    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.
    Interventions:
    • Drug: Abemaciclib
    • Drug: Trastuzumab
  • Active Comparator: Trastuzumab + Standard of Care Chemotherapy
    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.
    Interventions:
    • Drug: Trastuzumab
    • Drug: Standard of Care Single Agent Chemotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 3, 2016)
225
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 26, 2021
Actual Primary Completion Date April 8, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • diagnosis of HR+, HER2+ breast cancer (BC)
  • unresectable locally advanced recurrent BC or metastatic BC
  • adequate tumor tissue available 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
  • are able to swallow capsules

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
  • have received any recent (within 28 days prior to randomization) live virus vaccination
  • hypersensitivity to trastuzumab, murine proteins, fulvestrant, or to any of the excipients
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Brazil,   Canada,   France,   Germany,   Greece,   Italy,   Korea, Republic of,   Mexico,   Spain,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02675231
Other Study ID Numbers  ICMJE 15804
I3Y-MC-JPBZ ( Other Identifier: Eli Lilly and Company )
2015-003400-24 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
URL: https://vivli.org/
Responsible Party Eli Lilly and Company
Study Sponsor  ICMJE Eli Lilly and Company
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Eli Lilly and Company
PRS Account Eli Lilly and Company
Verification Date August 15, 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP