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

NCT ID: NCT02675231

Last Updated: 2024-11-26

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

237 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-05-23

Study Completion Date

2023-11-09

Brief Summary

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The purpose of this study is to evaluate the effectiveness of abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus physicians choice standard of care 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

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Conditions

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Hormone Receptor Positive Breast Cancer HER-2 Positive Breast Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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150 mg Abemaciclib + 8 mg/kg Trastuzumab + 500 mg Fulvestrant

150 milligram (mg) abemaciclib given orally every 12 hours (Q12H) of a 21-day cycle; plus 8 milligram per kilogram (mg/kg) trastuzumab intravenous (IV) infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle; plus 500 mg fulvestrant intramuscularly (IM) on day 1, 15 and 29 and then once every 4 weeks thereafter.

Group Type EXPERIMENTAL

Abemaciclib

Intervention Type DRUG

Administered Orally

Trastuzumab

Intervention Type DRUG

Administered IV

Fulvestrant

Intervention Type DRUG

Administered IM

150 mg Abemaciclib + 8 mg/kg Trastuzumab

150 mg abemaciclib given orally Q12H of a 21-day cycle; plus 8 mg/kg trastuzumab IV infusion on Day 1 of the cycle then a 6 mg/kg maintenance dose IV infusion on Day 1 of each subsequent cycle.

Group Type EXPERIMENTAL

Abemaciclib

Intervention Type DRUG

Administered Orally

Trastuzumab

Intervention Type DRUG

Administered IV

8 mg/kg Trastuzumab + Standard of Care Chemotherapy

8 mg/kg trastuzumab IV infusion on Day 1 of a 21-day cycle then a 6 mg/kg 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

Group Type ACTIVE_COMPARATOR

Trastuzumab

Intervention Type DRUG

Administered IV

Standard of Care Single Agent Chemotherapy

Intervention Type DRUG

Standard-of-care single-agent chemotherapy of physician's choice administered according to product label

Interventions

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Abemaciclib

Administered Orally

Intervention Type DRUG

Trastuzumab

Administered IV

Intervention Type DRUG

Fulvestrant

Administered IM

Intervention Type DRUG

Standard of Care Single Agent Chemotherapy

Standard-of-care single-agent chemotherapy of physician's choice administered according to product label

Intervention Type DRUG

Other Intervention Names

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LY2835219

Eligibility Criteria

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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 due to surgical / natural menopause or chemical ovarian suppression
* 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 if 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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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Comprehensive Blood and Cancer Center

Bakersfield, California, United States

Site Status

St Jude Medical Center

Fullerton, California, United States

Site Status

TRIO - Translational Research in Oncology-US, Inc.

Los Angeles, California, United States

Site Status

USC Norris Cancer Hospital

Los Angeles, California, United States

Site Status

UCLA Medical Center

Los Angeles, California, United States

Site Status

Cancer Care Associates Medical Group

Redondo Beach, California, United States

Site Status

Central Coast Medical Oncology Corporation

Santa Monica, California, United States

Site Status

Catholic Health Initiatives (CHI)

Englewood, Colorado, United States

Site Status

Florida Cancer Specialists

Fort Myers, Florida, United States

Site Status

Florida Cancer Specialists

Fort Myers, Florida, United States

Site Status

MD Anderson Cancer Center Orlando

Orlando, Florida, United States

Site Status

University of Miami Plantation

Plantation, Florida, United States

Site Status

Florida Cancer Specialists

St. Petersburg, Florida, United States

Site Status

Winship Cancer Center Emory University

Atlanta, Georgia, United States

Site Status

Northside Hospital Cancer Institute

Atlanta, Georgia, United States

Site Status

Fort Wayne Medical Oncology & Hematology, Inc.

Fort Wayne, Indiana, United States

Site Status

St Joseph Cancer Center

Lexington, Kentucky, United States

Site Status

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Billings Clinic Research Center

Billings, Montana, United States

Site Status

Brookdale Hospital Medical Center

Brooklyn, New York, United States

Site Status

North Shore Hematology Oncology Associates

East Setauket, New York, United States

Site Status

Clinical Research Alliance, Inc

Lake Success, New York, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

University of Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Site Status

Sarah Cannon Cancer Center

Nashville, Tennessee, United States

Site Status

Tennessee Oncology PLLC

Nashville, Tennessee, United States

Site Status

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Site Status

Northwest Medical Specialties, PLLC

Puyallup, Washington, United States

Site Status

Swedish Medical Center

Seattle, Washington, United States

Site Status

Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

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Buenos Aires, , Argentina

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CABA, , Argentina

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Córdoba, , Argentina

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Córdoba, , Argentina

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La Rioja, , Argentina

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Rosario, , Argentina

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Rosario, , Argentina

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San Miguel de Tucumán, , Argentina

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Viedma, , Argentina

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Kurralta Park, , Australia

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Nedlands, , Australia

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St Leonards, , Australia

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Charleroi, , Belgium

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Ghent, , Belgium

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Universitair Ziekenhuis Leuven - Gasthuisberg

Leuven, , Belgium

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Namur, , Belgium

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Porto Alegre, , Brazil

Site Status

Instituto COI de Pesquisa Educação e Gestão

Rio de Janeiro, , Brazil

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São Paulo, , Brazil

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Fundação Antonio Prudente - Hospital do Câncer A.C Camargo

São Paulo, , Brazil

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São Paulo, , Brazil

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Calgary, , Canada

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Calgary, , Canada

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Newmarket, , Canada

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Ottawa, , Canada

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Angers, , France

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Besançon, , France

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Lyon, , France

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Montpellier, , France

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Nice, , France

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Paris, , France

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Saint-Cloud, , France

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Villejuif, , France

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Frankfurt am Main, , Germany

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Freiburg im Breisgau, , Germany

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Hamburg, , Germany

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München, , Germany

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Achaia, , Greece

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Athens, , Greece

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Genova, , Italy

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Milan, , Italy

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Sora, , Italy

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Mexico City, , Mexico

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México, , Mexico

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México, , Mexico

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Daegu, , South Korea

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Goyang-si, , South Korea

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Seongnam-si, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

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Badajoz, , Spain

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Barcelona, , Spain

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Madrid, , Spain

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Madrid, , Spain

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Seville, , Spain

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Leicester, , United Kingdom

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Manchester, , United Kingdom

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Sutton, , United Kingdom

Site Status

Countries

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United States Argentina Australia Belgium Brazil Canada France Germany Greece Italy Mexico South Korea Spain United Kingdom

References

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Tolaney SM, Goel S, Nadal J, Denys H, Borrego MR, Litchfield LM, Liu J, Appiah AK, Chen Y, Andre F. Overall Survival and Exploratory Biomarker Analyses of Abemaciclib plus Trastuzumab with or without Fulvestrant versus Trastuzumab plus Chemotherapy in HR+, HER2+ Metastatic Breast Cancer Patients. Clin Cancer Res. 2024 Jan 5;30(1):39-49. doi: 10.1158/1078-0432.CCR-23-1209.

Reference Type DERIVED
PMID: 37906649 (View on PubMed)

Tolaney SM, Wardley AM, Zambelli S, Hilton JF, Troso-Sandoval TA, Ricci F, Im SA, Kim SB, Johnston SR, Chan A, Goel S, Catron K, Chapman SC, Price GL, Yang Z, Gainford MC, Andre F. Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with hormone receptor-positive, HER2-positive advanced breast cancer (monarcHER): a randomised, open-label, phase 2 trial. Lancet Oncol. 2020 Jun;21(6):763-775. doi: 10.1016/S1470-2045(20)30112-1. Epub 2020 Apr 27.

Reference Type DERIVED
PMID: 32353342 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://trials.lilly.com/en-US/find/completed?trialname=%20I3Y-MC-JPBZ&externalRequestID=68cbce79-fbf1-46c5-852a-338ca6e2be85

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

Other Identifiers

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I3Y-MC-JPBZ

Identifier Type: OTHER

Identifier Source: secondary_id

2015-003400-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

15804

Identifier Type: -

Identifier Source: org_study_id

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