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A Study of Abemaciclib (LY2835219) Plus Hormone Therapy in Participants With Early Breast Cancer

Phase 3
Terminated
Conditions
Breast Neoplasms
Interventions
Drug: Standard Adjuvant ET
Drug: Placebo
Registration Number
NCT04752332
Lead Sponsor
Eli Lilly and Company
Brief Summary

The main purpose of this study is to measure how well abemaciclib works in participants with early breast cancer who are taking hormone therapy after surgery. Participants must have breast cancer that is hormone receptor positive (HR+) and human epidermal receptor 2 positive (HER2+). Your participation could last up to 10 years depending on how you and your tumor respond.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
111
Inclusion Criteria
  • Have confirmed HR+, HER2+ early invasive breast cancer without evidence of disease recurrence or distant metastases

  • Have undergone definitive surgery of the primary breast tumor(s)

  • Have tumor tissue from breast (preferred) or lymph node

  • Have received a minimum of four cycles of chemotherapy in either the neoadjuvant or adjuvant setting per standard of care

  • Have completed approximately nine to 20 months of standard HER2-targeted therapy (neoadjuvant/adjuvant combined duration)

  • Have received one of the following eligible HER2-targeted adjuvant regimens AND be randomized within 12 weeks of completing the regimen:

    • For participants treated with neoadjuvant therapy and HER2-targeted therapy: A minimum of 4 cycles of T-DM1 in the adjuvant setting. NOTE: Participants may have received up to approximately 6 cycles of adjuvant trastuzumab prior to initiation of T-DM1. Additionally, participants may have switched to trastuzumab-based therapy (monotherapy or in combination with other HER2-targeted therapies) after 4 cycles of T-DM1
    • For participants who had definitive surgery prior to systemic therapy, a minimum of 4 cycles of adjuvant pertuzumab with trastuzumab.
  • Have high risk disease, defined by one of the following criteria:

    • Those who received neoadjuvant chemotherapy along with HER2-targeted treatment must have:

      • residual disease in at least one axillary lymph node, or
      • a residual tumor ≥ 5 cm, or
      • a residual tumor of any size that has direct extension to the chest wall and/or skin (ulceration or skin nodules).
    • Those who had definitive surgery prior to systemic therapy and completed adjuvant chemotherapy along with HER2-targeted therapies (trastuzumab and pertuzumab) must have

      • tumor involvement in ≥4 ipsilateral axillary lymph nodes, or
      • tumor involvement in 1 to 3 ipsilateral axillary lymph node(s) and histological Grade 3, or
      • primary invasive tumor size of ≥ 5 cm on pathological evaluation.
Exclusion Criteria
  • Have breast cancer with any of the following features:

    • Disease recurrence or distant metastatic disease (including contralateral axillary lymph nodes)
    • Pathological complete response from any prior early breast cancer treatments. Participants are required to have residual primary tumor and/or lymph node disease at the time of definitive surgery as indicated in inclusion criteria.
    • Inflammatory breast cancer
  • Have other medical conditions including:

    • Previous breast cancer (Exceptions: Ipsilateral ductal carcinoma in situ [DCIS] treated by locoregional therapy alone ≥5 years ago; contralateral DCIS treated by locoregional therapy at any time)
    • Other cancer being treated and/or not in complete remission within the last 5 years (Exceptions: Appropriately treated non-melanomatous skin cancer or carcinoma in situ of cervix, bladder, or colon)
    • Females who are pregnant or lactating
    • History of venous thromboembolism
    • Other serious medical conditions
  • Have previously received treatment with:

    • Any cyclin-dependent kinase (CDK)4 and CDK6 inhibitor
    • Prior adjuvant treatment with immunotherapy, tucatinib, neratinib, any investigational HER2 directed therapy, or T-DXd (DS8201) for treatment of breast cancer
    • Endocrine therapy (ET) (i.e., tamoxifen, raloxifene or aromatase inhibitor) for breast cancer prevention (without diagnosis of breast cancer)
    • Additional chemotherapy, anti-cancer ET, or HER2-targeted therapy beyond standard of care at study enrollment

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Abemaciclib Plus (+) Endocrine Therapy (ET)Standard Adjuvant ETAbemaciclib administered orally and standard adjuvant ET (physician's choice) administered according to package label.
Placebo + ETStandard Adjuvant ETPlacebo administered orally and standard adjuvant ET (physician's choice) administered according to package label.
Placebo + ETPlaceboPlacebo administered orally and standard adjuvant ET (physician's choice) administered according to package label.
Abemaciclib Plus (+) Endocrine Therapy (ET)AbemaciclibAbemaciclib administered orally and standard adjuvant ET (physician's choice) administered according to package label.
Primary Outcome Measures
NameTimeMethod
Invasive Disease Free Survival (IDFS)Randomization to Recurrence or Death from Any Cause (up to 10 Years)

IDFS as defined by the STEEP System

Secondary Outcome Measures
NameTimeMethod
Overall Survival (OS)Randomization to Death from Any Cause (up to 10 Years)

OS

Distant Relapse-Free Survival (DRFS)Randomization to Distant Recurrence or Death from Any Cause (up to 10 Years)

DRFS

Percentage of Participants with Central Nervous System (CNS) Metastases as First Site of Disease RecurrenceRandomization to Distant Recurrence or Death from Any Cause (up to 10 Years)

Percentage of Participants with CNS Metastases as First Site of Disease Recurrence

Change from Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scale ScoreCycle 1 up to end of Year 4

EORTC QLQ-C30 is a self-administered questionnaire with multidimensional scales that measures 5 functional domains (physical, role, cognitive, emotional, and social), global health status, and symptom scales of fatigue, pain, nausea and vomiting, dyspnea, loss of appetite, insomnia, constipation and diarrhea, and financial difficulties. A linear transformation is applied to standardize the raw scores to range between 0 and 100 per developer guidelines. For functional domains and global health status, higher scores represent a better level of functioning. For symptoms scales, higher scores represented a greater degree of symptoms.

Change from Baseline in the EuroQOL 5 Dimension 5 Level (EQ-5D 5L) Index ScoreCycle 1 up to end of Year 4

The EQ-5D is a self-administered questionnaire that participants complete to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a scale from 1 to 5 (no problem, slight problems, moderate problems, severe problems, and extreme problems/unable to, respectively). These combinations of attributes were converted into a weighted Health State Index score; the possible values for the Health State Index score range from less than 0 (0 equals health state of "dead"; severe problems in all 5 dimensions) to 1.0 (full health; no problem in any dimension). Higher score indicates better health state.

Pharmacokinetics (PK): Mean Steady State Concentrations of AbemaciclibDay 1 of Cycles 1-3 (Cycle = 28 days)

PK: Mean Steady State Concentrations of Abemaciclib

Trial Locations

Locations (114)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

🇨🇳

Guangzhou, Guangdong, China

Hainan Cancer Hospital

🇨🇳

Haikou, Hainan, China

Tongji Medical College of Huazhong University of Science and Technology

🇨🇳

Wuhan, Hubei, China

Hunan Cancer Hospital

🇨🇳

Changsha, Hunan, China

Fudan University Shanghai Cancer Center

🇨🇳

Shanghai, Shanghai, China

West China Hospital of Sichuan University

🇨🇳

Cheng Du, Sichuan, China

Ipswich Hospital

🇬🇧

Ipswich, Suffolk, United Kingdom

Institut de Cancérologie de Lorraine Alexis Vautrin

🇫🇷

Vandoeuvre-lès-Nancy, Meurthe-et-Moselle, France

Colchester General Hospital

🇬🇧

Colchester, Essex, United Kingdom

Florida Cancer Specialists - North

🇺🇸

Saint Petersburg, Florida, United States

Centro Medico San Roque

🇦🇷

San Miguel de Tucumán, Tucumán, Argentina

Instituto de Investigaciones Clínicas Mar del Plata

🇦🇷

Mar del Plata, Buenos Aires, Argentina

Centro Medico Privado CEMAIC

🇦🇷

Capital, Córdoba, Argentina

Sanatorio Parque

🇦🇷

Salta, Argentina

Ordensklinikum Linz

🇦🇹

Linz, Oberösterreich, Austria

CER San Juan

🇦🇷

San Juan, Argentina

Núcleo de Pesquisa Clínica da Rede São Camilo

🇧🇷

São Paulo, Brazil

Instituto de Educação, Pesquisa e Gestão em Saúde

🇧🇷

Rio de Janeiro, Brazil

Afflilated Hospital of Bengbu Medical College

🇨🇳

Bengbu, Anhui, China

Instituto de Ensino e Pesquisa São Lucas

🇧🇷

São Paulo, Brazil

Peking University People's Hospital

🇨🇳

Beijing, Beijing, China

Beijing Cancer hospital

🇨🇳

Beijing, Beijing, China

Fujian Medical University Union Hospital-1 Bingfanglou

🇨🇳

Fuzhou Fujian, Fujian, China

Xiangya Hospital Central South University

🇨🇳

Changsha, Hunan, China

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School

🇨🇳

Nanjing, Jiangsu, China

Tianjin Medical University Cancer Institute and Hospital

🇨🇳

Tianjin, Tianjin, China

Xinjiang Medical University Cancer Hospital - Urumqi

🇨🇳

Urumqi, Xinjiang, China

The First Affiliated Hospital, Zhejiang University

🇨🇳

Hangzhou, Zhejiang, China

The First People's Hospital of Hangzhou

🇨🇳

Hangzhou, Zhejiang, China

St. Vincenz-Krankenhaus Frauen- und Kinderklinik

🇩🇪

Paderborn, Nordrhein-Westfalen, Germany

General Oncology Hospital of Kifissia "Agioi Anargiroi"

🇬🇷

Nea Kifissia, Attikí, Greece

European Interbalkan Medical Center

🇬🇷

Thessaloniki, Greece

Petz Aladar Egyetemi Oktato Korhaz

🇭🇺

Gyor, Győr-Moson-Sopron, Hungary

Ospedale San Giovanni Moscati

🇮🇹

Statte, Taranto, Italy

Ospedale Mater Salutis

🇮🇹

Legnago, Verona, Italy

Nagoya City University Hospital

🇯🇵

Nagoya, Aichi, Japan

Ospedale Generale Provinciale Macerata

🇮🇹

Macerata, Italy

Chiba cancer center

🇯🇵

Chiba-shi, Chiba, Japan

Gunma Prefectural Cancer Center

🇯🇵

Ota, Gunma, Japan

Tsukuba University Hospital

🇯🇵

Tsukuba, Ibaraki, Japan

Ishikawa Prefectural Central Hospital

🇯🇵

Kanazawa, Ishikawa, Japan

Showa University Hospital

🇯🇵

Shinagawa, Tokyo, Japan

National Cancer Center Hospital

🇯🇵

Chuo-ku, Tokyo, Japan

National Hospital Organization Kyushu Cancer Center

🇯🇵

Fukuoka, Japan

Sagara Hospital

🇯🇵

Kagoshima, Japan

Osaka International Cancer Institute

🇯🇵

Osaka, Japan

Kumamoto Shinto General Hospital

🇯🇵

Kumamoto, Japan

National Hospital Organization Osaka Medical Center

🇯🇵

Osaka, Japan

St. Luke's International Hospital

🇯🇵

Tokyo, Japan

CHUAC-Hospital Teresa Herrera

🇪🇸

A Coruña, A Coruña [La Coruña], Spain

Centro Oncológico Internacional (COI)

🇲🇽

Guadalajara, Jalisco, Mexico

Hospital Universitario de Canarias

🇪🇸

San Cristobal de La laguna, Santa Cruz De Tenerife, Spain

Hospital Clinico San Carlos

🇪🇸

Madrid, Spain

Hospital Quirónsalud Valencia

🇪🇸

Valencia, Spain

Chang Gung Medical Foundation-Linkou Branch

🇨🇳

Taoyuan, Taiwan

Bristol Haematology and Oncology Centre

🇬🇧

Bristol, Bristol, City Of, United Kingdom

Royal Marsden Hospital

🇬🇧

Chelsea, London, United Kingdom

Palo Verde Cancer Specialists

🇺🇸

Glendale, Arizona, United States

Fundación Cenit Para La Investigación En Neurociencias

🇦🇷

Caba, Ciudad Autónoma De Buenos Aires, Argentina

Fundación CORI para la Investigación y Prevención del Cáncer

🇦🇷

La Rioja, Argentina

Peter MacCallum Cancer Centre

🇦🇺

Melbourne, Victoria, Australia

Jan Yperman ziekenhuis

🇧🇪

Ieper, West-Vlaanderen, Belgium

Calvary Mater Newcastle

🇦🇺

Waratah, New South Wales, Australia

AZ Maria Middelares

🇧🇪

Gent, Oost-Vlaanderen, Belgium

Instituto D'Or de Pesquisa e Ensino (IDOR)

🇧🇷

São Paulo, Brazil

NotreDame Intermedica Saude S.A

🇧🇷

São Paulo, Brazil

Hubei Cancer Hospital

🇨🇳

Wuhan, Hubei, China

The Third Hospital of Nanchang

🇨🇳

Nanchang, Jiangxi, China

Sichuan Cancer hospital

🇨🇳

Chengdu, Sichuan, China

LinYi Cancer Hospital

🇨🇳

Linyi, Shandong, China

CHU Besançon

🇫🇷

Besançon, Doubs, France

The Second Hospital of Jilin University

🇨🇳

Changchun, Jilin, China

Klinikum Ludwigsburg

🇩🇪

Ludwigsburg, Baden-Württemberg, Germany

Universitaetsklinikum Ulm

🇩🇪

Ulm, Baden-Württemberg, Germany

Universitätsmedizin Mannheim

🇩🇪

Mannheim, Baden-Württemberg, Germany

Alexandra Hospital

🇬🇷

Athina, Attikí, Greece

Euromedica General Clinic of Thessaloniki

🇬🇷

Thessaloniki, Thessaloníki, Greece

Sourasky Medical Center

🇮🇱

Tel Aviv, Tell Abīb, Israel

National Hospital Organization Shikoku Cancer Center

🇯🇵

Matsuyama, Ehime, Japan

St. Marianna University Hospital

🇯🇵

Kawasaki, Kanagawa, Japan

Hiroshima University Hospital

🇯🇵

Hiroshima, Japan

Shizuoka General Hospital

🇯🇵

Shizuoka, Japan

Inha University Hospital

🇰🇷

Incheon, Incheon-gwangyeoksi [Incheon], Korea, Republic of

Grupo Medico Camino Sc

🇲🇽

Mexico City, Distrito Federal, Mexico

CHA Bundang Medical Center, CHA University

🇰🇷

Seongnam-si, Kyǒnggi-do, Korea, Republic of

Seoul National University Bundang Hospital

🇰🇷

Seongnam, Kyǒnggi-do, Korea, Republic of

Korea University Anam Hospital

🇰🇷

Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Seoul-teukbyeolsi [Seoul], Korea, Republic of

Hospital Universitario 12 de Octubre

🇪🇸

Madrid, Madrid, Comunidad De, Spain

H.R.U Málaga - Hospital Materno-infantil

🇪🇸

Malaga, Málaga, Spain

Brustzentrum Ostschweiz

🇨🇭

St.Gallen, Sankt Gallen, Switzerland

Koo Foundation Sun Yat-Sen Cancer Center

🇨🇳

Taipei, Taiwan

The Christie

🇬🇧

Manchester, United Kingdom

Royal Marsden Hospital (Sutton)

🇬🇧

London, Sutton, United Kingdom

Centre Oscar Lambret

🇫🇷

Lille, Nord, France

Juntendo University Hospital

🇯🇵

Bunkyo-ku, Tokyo, Japan

National Taiwan University Hospital

🇨🇳

Taipei, Taiwan

Medizinische Universität Wien

🇦🇹

Vienna, Wien, Austria

Japanese Foundation for Cancer Research

🇯🇵

Koto, Tokyo, Japan

Kantonsspital Winterthur

🇨🇭

Winterthur, Zürich, Switzerland

Clinique Victor Hugo Le Mans

🇫🇷

Le Mans, Pays-de-la-Loire, France

TRIO-US (Translational Research in Oncology-US)

🇺🇸

Los Angeles, California, United States

Cornell-Beshore Cancer Institute

🇺🇸

Joplin, Missouri, United States

Millennium Oncology - Hollywood

🇺🇸

Hollywood, Florida, United States

Mt. Sinai Hospital PRiSMS

🇺🇸

Chicago, Illinois, United States

The Valley Hospital

🇺🇸

Ridgewood, New Jersey, United States

US Oncology

🇺🇸

The Woodlands, Texas, United States

Sarah Cannon Research Institute SCRI

🇺🇸

Nashville, Tennessee, United States

Texas Oncology - Medical City Dallas

🇺🇸

The Woodlands, Texas, United States

Northwest Cancer Specialists PC

🇺🇸

The Woodlands, Texas, United States

USO-Southern Cancer Center, P.C.

🇺🇸

The Woodlands, Texas, United States

Clinique Saint Pierre

🇧🇪

Ottignies, Wallonne, Région, Belgium

AZ Groeninge Campus Kennedylaan

🇧🇪

Kortrijk, West-Vlaanderen, Belgium

Charing Cross Hospital

🇬🇧

London, Hammersmith And Fulham, United Kingdom

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