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
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT05696626
- Lead Sponsor
- Sermonix Pharmaceuticals Inc.
- Brief Summary
The goal of this clinical trial is to assess the efficacy, safety and tolerability of the combination of lasofoxifene and abemaciclib compared to fulvestrant and abemaciclib for the treatment of pre- and postmenopausal women and men who have previously received ribociclib or palbociclib-based treatment and have locally advanced or metastatic estrogen receptor positive (ER+)/human epidermal growth factor 2 negative (HER2-) breast cancer with an estrogen receptor 1 (ESR1) mutation.
The main question the study aims to answer is:
• To compare the efficacy of the combination of lasofoxifene and abemaciclib with that of fulvestrant and abemaciclib Participants will receive either receive 5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day or the combination of fulvestrant 500 mg intramuscular (IM) on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
-
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.
-
Histological or cytological confirmation of ER+/HER2 - 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).
-
Able to understand and voluntarily sign a written informed consent before any screening procedures.
- 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, unless the event occurred greater than 6 months prior to screening and the subject is treated with chronic anticoagulant therapy such as apixaban (Eliquis) or rivaroxaban (Xarelto).
- 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 double-barrier contraception.
- Women who are breast feeding
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Reference Therapy Fulvestrant in combination with abemaciclib 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. Treatment Lasofoxifene in combination with abemaciclib 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.
- Primary Outcome Measures
Name Time Method Progression free survival (PFS) Within approximately 3 years PFS is defined as the time from the date of randomization \[Visit 0 (Day 1)\] to the earliest date of first documented progression per RECIST 1.1 or death due to any cause.
- Secondary Outcome Measures
Name Time Method Time to cytotoxic chemotherapy Within approximately 3 years From the date of randomization to the date of first documented use of cytotoxic chemotherapy.
Overall survival (OS) Within approximately 3 years Overall survival is defined as time from the date of Visit 0 (Day 1) to death due to any cause.
Clinical benefit rate (CBR) Within approximately 3 years CBR is defined as the percentage of subjects with best overall response of confirmed CR, confirmed PR, or stable disease (SD) with a duration of 24 weeks or longer according to RECIST 1.1. As used in this calculation, stable disease is defined as stable disease in those subjects with measurable disease plus nonPR/non progressive disease (PD) in subjects with non-measurable disease.
Duration of response (DoR) in subjects with an objective response Within approximately 3 years DoR is from the date of first documented confirmed response (CR or PR) to the date of first documented progression of disease or death due to any cause, whichever is earlier.
Objective response rate (ORR) Within approximately 3 years ORR is defined as the percentage of subjects with measurable disease at baseline whose best overall response is either a confirmed CR or a confirmed PR according to RECIST 1.1.
Time to response (TTR) in subjects with an objective response Within approximately 3 years TTR is from the date of randomization to the date of first documented confirmed response (CR or PR).
Quality of Life (QoL) evaluated using the Functional Assessment of Cancer Therapy-Breast Cancer-Endocrine Subscale (FACT B-ES) Within approximately 3 years Scale ranges from 'Not at all' to 'Very much'
Incidence of Adverse Events (AEs) and Serious AEs Within approximately 3 years The type, severity (graded by Common Terminology Criteria for Adverse Events \[CTCAE version 5.0\]), course, duration, seriousness, and relationship to study treatment will be assessed at each visit
Trial Locations
- Locations (176)
The First Hospital of Lanzhou University
🇨🇳Lanzhou, China
Linyi Cancer Hospital
🇨🇳Linyi, China
The First Affiliated Hospital of Henan University of Science and Technology
🇨🇳Luoyang, China
The Affiliated Hospital of Southwest Medical University (Luzhou Medical College)
🇨🇳Luzhou, China
Jiangxi Cancer Hospital
🇨🇳Nanchang, China
Nangchang People's Hospital
🇨🇳Nanchang, China
Nanjing Drum Tower Hospital
🇨🇳Nanjing, China
The Second People's Hospital of Neijiang
🇨🇳Neijiang, China
Ningbo Medical Center Li Huili Hospital
🇨🇳Ningbo, China
First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Shanxi, China
Guangxi Medical University Cancer Hospital
🇨🇳Nanning, China
Nanyang Central Hospital
🇨🇳Nanyang, China
The Affiliated Hospital of Qingdao University
🇨🇳Qingdao, China
Fudan University Cancer Center
🇨🇳Shang'ai, China
Qingdao Central Hospital, University of Health and Rehabilitation Sciences
🇨🇳Qingdao, China
The Central Hospital of Shaoyang
🇨🇳Shaoyang, China
Liaoning Cancer Hospital & Institute
🇨🇳Shenyang, China
Yuebei People's Hospital
🇨🇳Shouguang, China
University of Electonic Science & Technology (UESTC) - Sichuan Cancer Hospital & Institute
🇨🇳Sichuan, China
Tianjin Cancer Hospital Airport Hospital
🇨🇳Tianjin, China
Tianjin Medical University Cancer Institute & Hospital
🇨🇳Tianjin, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, China
Hubei Cancer Hospital
🇨🇳Wuhan, China
Union Hospital Tongji Medical College Huazhong University of Science and Technolog
🇨🇳Wuhan, China
The First Affiliated Hospital of Air Force Medical University
🇨🇳XI Ail, China
The first affiliated hospital of Xiamen University
🇨🇳Xiamen, China
Xuzhou Central Hospital
🇨🇳Xuzhou, China
Yuncheng Central Hospital
🇨🇳Yuncheng, China
Zhejiang cancer hospital
🇨🇳Zhejiang, China
Zhejiang Provincial People's Hospital
🇨🇳Zhejiang, China
Henan Cancer Hospital
🇨🇳Zhengzhou, China
The First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, China
Zhongshan City People's Hospital
🇨🇳Zhongshan, China
Zhumadian Central Hospital
🇨🇳Zhumadian, China
The Affiliated Cancer Hospital of Xinjiang Medical University
🇨🇳Ürümqi, China
Service d'Oncologie Medicale - CHRU Besancon
🇫🇷Besançon, France
Institut Bergonie
🇫🇷Bordeaux, France
Centre Francois Baclesse
🇫🇷CAEN Cedex 05, France
Centre Oscar Lambret
🇫🇷Lille, France
Centre Leon Berard
🇫🇷Lyon, France
Institut Paoli-Calmettes
🇫🇷Marseille, France
CHU Poitiers - Pole Regional de Cancerologie de Poitiers (PRC)
🇫🇷Poitiers, France
Centre Henri Becquerel
🇫🇷Rouen, France
Institut Claudius Regaud
🇫🇷Toulouse, France
Universitaetsklinikum Carl Gustav Carus Dresden
🇩🇪Dresden, Germany
Klinikum rechts der Isar der Technischen Universitaet Muenchen
🇩🇪München, Germany
Rambam Health Care Campus
🇮🇱Haifa, Israel
Hadassah Ein-Karem Medical Center
🇮🇱Jerusalem, Israel
Shaare Zedek Medical Center
🇮🇱Jerusalem, Israel
Rabin MC
🇮🇱Petach Tikva, Israel
Kaplan Medical Center
🇮🇱Reẖovot, Israel
Tel Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Sheba Medical Center
🇮🇱Tel HaShomer, Israel
Centro Riferimento Oncologico - Aviano
🇮🇹Aviano, Italy
IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino Amadori - IRST S.r.l.
🇮🇹Meldola, Italy
Istituto Europeo di Oncologia
🇮🇹Milano, Italy
Humanitas Istituto Clinico Catanese
🇮🇹Misterbianco, Italy
Azienda Ospedaliero-Universitaria di Modena
🇮🇹Modena, Italy
Istituto Nazionale Tumori IRCCS Fondazione G. Pascale
🇮🇹Napoli, Italy
Azienda Ospedaliero Universitaria di Parma
🇮🇹Parma, Italy
Fondazione IRCCS Policlinico San Matteo
🇮🇹Pavia, Italy
Fondazione Policlinico Universitario A. Gemelli IRCCS - Universita Cattolica del Sacro Cuore
🇮🇹Roma, Italy
Azienda Ospedaliera Universitaria Integrata Verona-Ospedale Borgo Trento
🇮🇹Verona, Italy
National Cancer Center
🇰🇷Gyeonggi-do, Korea, Republic of
Chonnam National University Hwasun Hospital
🇰🇷Hwasun, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
KO - MED Centra Kliniczne Sp. z o.o., Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej
🇵🇱Biała Podlaska, Poland
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach, I Klinika Radioterapii i Chemioterapii
🇵🇱Gliwice, Poland
Szpital Specjalistyczny im. Ludwika Rydygiera w Krakowie - Oddzial Onkologii Klinicznej z Pododdzialem Dziennym
🇵🇱Krakow, Poland
SP ZOZ Szpital Uniwersytecki w Krakowie, Oddzial Onkologii Klinicznej
🇵🇱Kraków, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu, Oddzial Chemioterapii
🇵🇱Poznań, Poland
Wielkopolskie Centrum Onkologii (WCO) / The Greater Poland Cancer Center
🇵🇱Poznań, Poland
Mazowiecki Szpital Onkologiczny
🇵🇱Wieliszew, Poland
Instytut Centrum Zdrowia Matki Polki - Klinika Onkologii
🇵🇱Łódź, Poland
Centrul Medical Focus
🇷🇴Bucharest, Romania
Filantropia Clinical Hospital
🇷🇴Bucharest, Romania
Radiotherapy Center Cluj
🇷🇴Cluj-Napoca, Romania
Onco Clinic Consult SA
🇷🇴Craiova, Romania
Oncology Center Sfantul Nectarie
🇷🇴Craiova, Romania
Gral Medical SRL
🇷🇴Piteşti, Romania
OncoMed Oncology Center
🇷🇴Timişoara, Romania
National Cancer Centre Singapore
🇸🇬Singapore, Singapore
Curie Oncology
🇸🇬Singapore, Singapore
Hospital Clinic Barcelona
🇪🇸Barcelona, Spain
Hospital Universitario Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Clinica Universidad de Navarra - Madrid
🇪🇸Madrid, Spain
Hospital Beata Maria Ana
🇪🇸Madrid, Spain
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario de La Princesa
🇪🇸Madrid, Spain
Hospital Regional Universitario de Malaga
🇪🇸Málaga, Spain
Clinica Universidad de Navarra - Pamplona
🇪🇸Pamplona, Spain
Instituto Valenciano de Oncologia
🇪🇸Valencia, Spain
Changhua Christian Hospital (CCH)
🇨🇳Changhua, Taiwan
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Tri-Service General Hospital
🇨🇳Taipei City, Taiwan
Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)
🇨🇳Kaohsiung, Taiwan
Koo Foundation Sun Yat-Sen Cancer Center
🇨🇳Taipei, Taiwan
Linkou Chang Gung Memorial Hospital (CGMHLK)
🇨🇳Taoyuan City, Taiwan
Leeds Teaching Hospitals NHS Trust
🇬🇧Leeds, United Kingdom
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Mayo Clinic - Phoenix
🇺🇸Phoenix, Arizona, United States
University of Arizona - Cancer Center
🇺🇸Tucson, Arizona, United States
California Research Institute
🇺🇸Los Angeles, California, United States
Providence Medical Foundation - Santa Rosa, CA
🇺🇸Santa Rosa, California, United States
Boca Raton Regional Hospital
🇺🇸Boca Raton, Florida, United States
Mayo Clinic - Jacksonville
🇺🇸Jacksonville, Florida, United States
Miami Cancer Institute
🇺🇸Miami, Florida, United States
Miami Cancer Institute Plantation
🇺🇸Plantation, Florida, United States
Emory University School of Medicine
🇺🇸Atlanta, Georgia, United States
Norton Cancer Institute
🇺🇸Louisville, Kentucky, United States
Johns Hopkins Kimmel Cancer Center
🇺🇸Baltimore, Maryland, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Charing Cross Hospital
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Cancer and Hematology Centers of Western Michigan
🇺🇸Grand Rapids, Michigan, United States
Allina Health System DBA Virginia Piper Cancer Institute
🇺🇸Minneapolis, Minnesota, United States
Mayo Clinic - Rochester
🇺🇸Rochester, Minnesota, United States
Saint Luke's Cancer Institute
🇺🇸Kansas City, Missouri, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Renown Regional Medical Centre
🇺🇸Reno, Nevada, United States
New Jersey Cancer Care, PA
🇺🇸Belleville, New Jersey, United States
CHU UCL Namur - Site De Sainte-Elisabeth
🇧🇪Namur, Belgium
Icahn School of Medicine at Mount Sinai
🇺🇸New York, New York, United States
David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Nottingham City Hospital
🇬🇧Nottingham, United Kingdom
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Altru Health Systems
🇺🇸Grand Forks, North Dakota, United States
The Ohio State University Comprehensive Cancer Center - Arthur G. James Cancer Hospital and Richard J. Solovev Research Institute (OSUCCC - James)
🇺🇸Columbus, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Lyndon B. Johnson Hospital
🇺🇸Houston, Texas, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Harris Health System - Smith Clinic
🇺🇸Houston, Texas, United States
Blacktown Hospital
🇦🇺Blacktown, Australia
Concord Repatriation General Hospital
🇦🇺Concord, Australia
Mater Misericordiae Ltd, South Brisbane
🇦🇺South Brisbane, Australia
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Antwerp University Hospital (UZA)
🇧🇪Edegem, Belgium
Universitaire Ziekenhuizen Leuven
🇧🇪Leuven, Belgium
The Ottawa General Hospital
🇨🇦Ottawa, Ontario, Canada
Sunnybrook Health Sciences Centre -Bayview Campus
🇨🇦Toronto, Ontario, Canada
Hospital Maisonneuve-Rosemont
🇨🇦Montréal, Quebec, Canada
Lady Davis Institute for Medical Research Jewish General Hospital
🇨🇦Montréal, Quebec, Canada
CIUSSS du Saguenay-Lac-Saint-Jean
🇨🇦Saguenay, Quebec, Canada
Anhui Provincial Cancer Hospital
🇨🇳Anhui, China
Beijing Cancer Hospital
🇨🇳Beijing, China
The First Affiliated Hospital of Bengbu Medical University
🇨🇳Bengbu, China
The First Hospital of Jilin University
🇨🇳Changchun, China
The Second Xiangya Hospital of Central South University
🇨🇳Changsha, China
Sichuan Provincial People's Hospital
🇨🇳Chengdu, China
West China Hospital, Sichuan University
🇨🇳Chengdu, China
The First Affiliated Hospital, Chongqing Medical University
🇨🇳Chongqi, China
The Second Hospital of Dalian Medical University
🇨🇳Dalian, China
Deyang People's Hospital
🇨🇳Deyang, China
Fuyang Cancer Hosptial
🇨🇳Fuyang, China
Fujian Cancer Hospital
🇨🇳Fuzhou, China
Fujian Medical University Union Hospital
🇨🇳Fuzhou, China
Zhujiang Hospital of Nanfang Medical University
🇨🇳Guandong, China
Guangdong Provincial People's Hospital
🇨🇳Guangdong, China
Meizhou People's Hospital
🇨🇳Guangdong, China
Peking University Shenzhen Hospital
🇨🇳Guangdong, China
Sun Yat-Sen University- Cancer Center
🇨🇳Guangdong, China
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
🇨🇳Hangzhou, China
The First Affiliated Hospital, College of Medicine, Zhejiang University
🇨🇳Hangzhou, China
Zhejiang Provincial Hospital of Chinese Medicine
🇨🇳Hangzhou, China
Hebei Medical University - The Fourth Hospital - Hebei Provincial Tumor Hospital
🇨🇳Hebei, China
Xiangyang Central Hospital
🇨🇳Hubei, China
Xiangya Hospital Central South University
🇨🇳Hunan, China
Shandong Province Tumor Hospital
🇨🇳Jinan, China
Gansu Provincial Hospital
🇨🇳Lanzhou, China