Evaluation of Lasofoxifene Combined With Abemaciclib Compared With Fulvestrant Combined With Abemaciclib in Locally Advanced or Metastatic ER+/HER2- Breast Cancer With an ESR1 Mutation (ELAINEIII)
Metastatic Breast Cancer
About this trial
This is an interventional treatment trial for Metastatic Breast Cancer
Eligibility Criteria
Inclusion Criteria: Pre- or postmenopausal women or men. Locally advanced and/or metastatic ER+ breast cancer with radiological or clinical evidence of progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease. No evidence of progression for at least 6 months on an AI/CDKi combination for advanced breast cancer. At least 1 or more ESR1 point mutations in the ESR1 ligand binding domain as assessed in cell- free ctDNA obtained from a blood or breast cancer tissue. Locally advanced or metastatic breast cancer with either measurable (according to RECIST 1.1) or non-measurable lesions. Subjects may have received 1 cytotoxic chemotherapy regimen in the metastatic disease setting prior to study entry, but must have recovered from chemotherapy acute toxicity excluding alopecia and Grade 2 peripheral neuropathy. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 Adequate organ function Able to swallow tablets Brain metastases are allowed only if the following 4 parameters hold: Asymptomatic, Definitively treated (e.g., radiotherapy, surgery), Not requiring steroids up to 4 weeks before study treatment initiation, AND Central nervous system disease stable for >3 months prior to registration as documented by magnetic resonance imagining (MRI). 10. Able to understand and voluntarily sign a written informed consent before any screening procedures. Exclusion Criteria: Lymphangitic carcinomatosis involving the lung. History of Grade 3 or Grade 4 interstitial lung disease (ILD) on previous therapy. Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator. Prior progression of disease on abemaciclib, fulvestrant, or other selective estrogen receptor degrader (SERD) therapy. Subjects with a known hypersensitivity to fulvestrant or to any of the excipients Radiotherapy within 30 days prior to Visit 0 (Day 1) except in case of localized radiotherapy for analgesic purposes or for lytic lesions at risk of fracture, which can then be completed within 7 days prior to Visit 0 (Day 1). Subjects must have recovered from radiotherapy toxicities prior to Visit 0 (Day 1). Known RB1 mutations or deletions that in the opinion of the investigator confer resistance to CDK4/6i. (Screening for RB1 mutation is not required for entry.) History of long QTc (Q-T interval corrected for heart rate) syndrome or a QTc of >480 msec. History of a pulmonary embolus (PE), deep vein thrombosis (DVT), or any known thrombophilia. Lasofoxifene is not recommended for use in subjects with conditions that place them at increased risk for VTEs (such as severe congestive heart failure [CHF] or prolonged immobilization). On concomitant strong CYP3A4 inhibitors. On strong and moderate CYP3A4 inducers. Any significant co-morbidity that would impact the study or the subject's safety, including subjects with significant malabsorption. Active systemic bacterial or fungal infection (requiring intravenous [IV] antibiotics or antifungals at the time of initiating study treatment). Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). History of malignancy within the past 5 years (excluding breast cancer), except basal cell or squamous cell carcinoma of the skin curatively treated by surgery. Positive serum pregnancy test (only if premenopausal). Sexually active premenopausal women and men unwilling to use contraception. History of non-compliance to medical regimens. Unwilling or unable to comply with the protocol. Current participation in any clinical research trial involving an investigational drug or device within the last 30 days.
Sites / Locations
- Mayo Clinic - Scottsdale
- University of Arizona - Cancer Center
- California Research Institute
- Providence Medical Foundation - Santa Rosa, CA
- Boca Raton Regional Hospital
- Mayo Clinic - Jacksonville
- Miami Cancer Institute
- Miami Cancer Institute Plantation
- Emory University School of Medicine
- Norton Cancer Institute
- Hematology Oncology Clinic
- Johns Hopkins Kimmel Cancer Center
- Massachusetts General Hospital
- Dana-Farber Cancer Institute
- Henry Ford Health System
- Cancer and Hematology Centers of Western Michigan
- Mayo Clinic - Rochester
- Saint Luke's Cancer Institute
- Washington University School of Medicine
- University of Nebraska Medical Center
- New Jersey Cancer Care, PA
- Icahn School of Medicine at Mount Sinai
- David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
- Duke University Medical Center
- The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solovev Research Institute (OSUCCC - James)
- Oklahoma University Health Sciences Center
- University of Pittsburgh Medical Center
- Chattanooga Oncology Hematology Care - Tennessee Oncology
- Vanderbilt University Medical Center
- Lyndon B. Johnson Hospital
- Baylor College of Medicine
- MD Anderson Cancer Center
- Flinders Medical Centre
- Blacktown Hospital
- Concord Repatriation General Hospital
- Mater Misericordiae Ltd, South Brisbane
- Cliniques Universitaires Saint-Luc
- Antwerp University Hospital (UZA)
- Universitaire Ziekenhuizen Leuven
- Clinique CHC MontLégia
- CHU UCL Namur - Site De Sainte-Elisabeth
- The Ottawa General Hospital
- Sunnybrook Health Sciences Centre -Bayview Campus
- Hospital Maisonneuve-Rosemont
- Hospital Notre Dame du CHUM
- Lady Davis Institute for Medical Research Jewish General Hospital
- CIUSSS du Saguenay-Lac-Saint-Jean
- Masarykuv onkologicky ustav
- Fakultni nemocnice Hradec Kralove
- Fakultni nemocnice Olomouc - Oncology clinic
- Fakultní nemocnice v Motole
- Service d'Oncologie Medicale - CHRU Besancon
- Institut Bergonie
- Centre Francois Baclesse
- Centre Oscar Lambret
- Centre Leon Berard
- Institut Paoli-Calmettes
- CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)
- Centre Henri Becquerel
- Institut de cancerologie Strasbourg Europe (ICANS)
- Institut Claudius Regaud
- Universitaetsklinikum Carl Gustav Carus Dresden
- Universitaetsklinikum Ulm
- Budapesti Uzsoki Utcai Korhaz
- Debreceni Egyetem Klinikai Kozpont
- Rambam Health Care Campus
- Hadassah Ein-Karem Medical Center
- Shaare Zedek Medical Center
- Rabin MC
- Kaplan Medical Center
- Tel Aviv Sourasky Medical Center
- Sheba Medical Center
- Centro Riferimento Oncologico - Aviano
- IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l.
- Istituto Europeo di Oncologia
- Humanitas Istituto Clinico Catanese
- Azienda Ospedaliero-Universitaria di Modena
- Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
- Azienda Ospedaliero Universitaria di Parma
- Fondazione IRCCS Policlinico San Matteo
- Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
- Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento
- National Cancer Center
- Asan Medical Center
- Korea University Anam Hospital
- Severance Hospital, Yonsei University Health System
- KO - MED Centra Kliniczne Sp. z o.o., Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
- Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii
- Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach, I Klinika Radioterapii i Chemioterapii
- Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Klinika Onkologii Klinicznej
- Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie - Oddzial Onkologii Klinicznej z Pododdzialem Dziennym
- SP ZOZ Szpital Uniwersytecki w Krakowie, Oddzial Onkologii Klinicznej
- NeuroMed
- Uniwersytecki Szpital Kliniczny w Poznaniu, Oddzial Chemioterapii
- Wielkopolskie Centrum Onkologii (WCO) / The Greater Poland Cancer Center
- Mazowiecki Szpital Onkologiczny
- Instytut Centrum Zdrowia Matki Polki - Klinika Onkologii
- Centrul Medical Focus
- Filantropia Clinical Hospital
- Radiotherapy Center Cluj
- Onco Clinic Consult SA
- Oncology Center Sfantul Nectarie
- Gral Medical SRL
- OncoMed Oncology Center
- Hospital Clinic Barcelona
- Hospital Universitario Vall d'Hebron
- Hospital Universitario Reina Sofia
- Clinica Universidad de Navarra - Madrid
- Hospital General Universitario Gregorio Maranon
- Hospital Universitario 12 de Octubre
- Hospital Universitario de La Princesa
- Hospital Regional Universitario de Malaga
- Clinica Universidad de Navarra - Pamplona
- Instituto Valenciano de Oncologia
- Changhua Christian Hospital (CCH)
- Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
- National Cheng Kung University Hospital
- Tri-Service General Hospital
- Koo Foundation Sun Yat-Sen Cancer Center
- National Taiwan University Hospital
- Linkou Chang Gung Memorial Hospital (CGMHLK)
- Trakya University Medical Faculty
- Kocaeli University Faculty of Medicine
- Ankara University Medical Faculty Medical Oncology Department
- Uludag University Medical Faculty
- Liv Hospital Ankara
- Goztepe Prof. Dr. Suleyman Yalcin City Hospital
- Medical Point Izmir Hospital
- Suat Seren Training and Research Hospital
- West Middlesex University Hospital
- Leeds Teaching Hospitals NHS Trust
- The Christie NHS Foundation Trust
- Nottingham City Hospital
- Lancashire Teaching Hospitals
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Treatment
Reference Therapy
Pre- and Postmenopausal Women and Men with locally advanced or metastatic ER+/HER2- breast cancer who have disease progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease and who have an ESR1 mutation.
Pre- and Postmenopausal Women and Men with locally advanced or metastatic ER+/HER2- breast cancer who have disease progression on an AI in combination with either palbociclib or ribociclib as their first hormonal treatment for metastatic disease and who have an ESR1 mutation.