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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05696626
Other study ID # SMX 22-002
Secondary ID
Status Recruiting
Phase Phase 3
First received
Last updated
Start date October 31, 2023
Est. completion date June 2026

Study information

Verified date June 2024
Source Sermonix Pharmaceuticals Inc.
Contact Sermonix Pharmaceuticals Study Inquiry
Phone 614-864-4919
Email info@sermonixpharma.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Recruiting
Enrollment 400
Est. completion date June 2026
Est. primary completion date June 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Pre- or postmenopausal women or men. 2. 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. 3. Histological or cytological confirmation of ER+/HER2 - disease 4. No evidence of progression for at least 6 months on an AI/CDKi combination for advanced breast cancer. 5. 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. 6. Locally advanced or metastatic breast cancer with either measurable (according to RECIST 1.1) or non-measurable lesions. 7. 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. 8. Eastern Cooperative Oncology Group (ECOG) performance score of 0 or 1 9. Adequate organ function 10. Able to swallow tablets 11. Brain metastases are allowed only if the following 4 parameters hold: 1. Asymptomatic, 2. Definitively treated (e.g., radiotherapy, surgery), 3. Not requiring steroids up to 4 weeks before study treatment initiation, AND 4. Central nervous system disease stable for >3 months prior to registration as documented by magnetic resonance imagining (MRI). 12. Able to understand and voluntarily sign a written informed consent before any screening procedures. Exclusion Criteria: 1. Lymphangitic carcinomatosis involving the lung. 2. History of Grade 3 or Grade 4 interstitial lung disease (ILD) on previous therapy. 3. Visceral crisis in need of cytotoxic chemotherapy as assessed by the investigator. 4. Prior progression of disease on abemaciclib, fulvestrant, or other selective estrogen receptor degrader (SERD) therapy. 5. Subjects with a known hypersensitivity to fulvestrant or to any of the excipients 6. 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). 7. 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.) 8. History of long QTc (Q-T interval corrected for heart rate) syndrome or a QTc of >480 msec. 9. History of a pulmonary embolus (PE), deep vein thrombosis (DVT), or any known thrombophilia. 10. 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). 11. On concomitant strong CYP3A4 inhibitors. 12. On strong and moderate CYP3A4 inducers. 13. Any significant co-morbidity that would impact the study or the subject's safety, including subjects with significant malabsorption. 14. Active systemic bacterial or fungal infection (requiring intravenous [IV] antibiotics or antifungals at the time of initiating study treatment). 15. Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). 16. 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. 17. Positive serum pregnancy test (only if premenopausal). 18. Sexually active premenopausal women and men unwilling to use double-barrier contraception. 19. Women who are breast feeding 20. History of non-compliance to medical regimens. 21. Unwilling or unable to comply with the protocol. 22. Current participation in any clinical research trial involving an investigational drug or device within the last 30 days.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Lasofoxifene in combination with abemaciclib
5 mg/d of oral lasofoxifene plus oral abemaciclib 150 mg twice a day
Fulvestrant in combination with abemaciclib
Fulvestrant 500 mg intramuscular (IM) on Days 1, 15, and 29 and then once monthly thereafter plus oral abemaciclib 150 mg twice a day

Locations

Country Name City State
Australia Blacktown Hospital Blacktown
Australia Concord Repatriation General Hospital Concord
Australia Mater Misericordiae Ltd, South Brisbane South Brisbane
Belgium Cliniques Universitaires Saint-Luc Brussels
Belgium Antwerp University Hospital (UZA) Edegem
Belgium Universitaire Ziekenhuizen Leuven Leuven
Belgium Clinique CHC MontLégia Liège
Belgium CHU UCL Namur - Site De Sainte-Elisabeth Namur
Canada Hospital Maisonneuve-Rosemont Montréal Quebec
Canada Lady Davis Institute for Medical Research Jewish General Hospital Montréal Quebec
Canada The Ottawa General Hospital Ottawa Ontario
Canada Sunnybrook Health Sciences Centre -Bayview Campus Toronto Ontario
Czechia Masarykuv onkologicky ustav Brno
Czechia Fakultni nemocnice Hradec Kralove Hradec Králové
Czechia Fakultni nemocnice Olomouc - Oncology clinic Olomouc
Czechia Fakultní nemocnice v Motole Praha 5
France 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 de cancerologie Strasbourg Europe (ICANS) Strasbourg
France Institut Claudius Regaud Toulouse
Germany Universitaetsklinikum Carl Gustav Carus Dresden Dresden
Germany Universitaetsklinikum Ulm Ulm
Hungary Budapesti Uzsoki Utcai Korhaz Budapest
Israel 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 Re?ovot
Israel Tel Aviv Sourasky Medical Center Tel Aviv
Israel Sheba Medical Center Tel HaShomer
Italy 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
Korea, Republic of 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
Poland KO - MED Centra Kliniczne Sp. z o.o., Wojewodzki Szpital Specjalistyczny w Bialej Podlaskiej Biala Podlaska
Poland Uniwersyteckie Centrum Kliniczne, Klinika Onkologii i Radioterapii Gdansk
Poland Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy, Oddzial w Gliwicach, I Klinika Radioterapii i Chemioterapii Gliwice
Poland Swietokrzyskie Centrum Onkologii Samodzielny Publiczny Zaklad Opieki Zdrowotnej, Klinika Onkologii Klinicznej Kielce
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 Instytut Centrum Zdrowia Matki Polki - Klinika Onkologii Lódz
Poland NeuroMed Lublin
Poland Wielkopolskie Centrum Onkologii (WCO) / The Greater Poland Cancer Center Poznan
Poland Mazowiecki Szpital Onkologiczny Wieliszew
Romania 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 Pitesti
Romania OncoMed Oncology Center Timisoara
Singapore Curie Oncology Singapore
Singapore National Cancer Centre Singapore Singapore
Spain 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 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
Taiwan Changhua Christian Hospital (CCH) Changhua
Taiwan Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH) Kaohsiung
Taiwan National Cheng Kung University Hospital Tainan
Taiwan Koo Foundation Sun Yat-Sen Cancer Center Taipei
Taiwan National Taiwan University Hospital Taipei
Taiwan Tri-Service General Hospital Taipei City
Taiwan Linkou Chang Gung Memorial Hospital (CGMHLK) Taoyuan City
Turkey Ankara University Medical Faculty Medical Oncology Department Ankara
Turkey Uludag University Medical Faculty Bursa
Turkey Liv Hospital Ankara Cankaya
Turkey Goztepe Prof. Dr. Suleyman Yalcin City Hospital Istanbul
Turkey Medical Point Izmir Hospital Izmir
Turkey Suat Seren Training and Research Hospital Izmir
Turkey Kocaeli University Faculty of Medicine Izmit Kocaeli
Turkey Trakya University Medical Faculty Merkez Edirne
United Kingdom West Middlesex University Hospital Isleworth
United Kingdom Leeds Teaching Hospitals NHS Trust Leeds
United Kingdom The Christie NHS Foundation Trust Manchester
United Kingdom Nottingham City Hospital Nottingham
United Kingdom Lancashire Teaching Hospitals Preston
United States Emory University School of Medicine Atlanta Georgia
United States Johns Hopkins Kimmel Cancer Center Baltimore Maryland
United States Hematology Oncology Clinic Baton Rouge Louisiana
United States New Jersey Cancer Care, PA Belleville New Jersey
United States Boca Raton Regional Hospital Boca Raton Florida
United States Beth Israel Deaconess Medical Center Boston Massachusetts
United States Dana-Farber Cancer Institute Boston Massachusetts
United States Massachusetts General Hospital Boston Massachusetts
United States University of Vermont Medical Center Burlington Vermont
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 Duke University Medical Center Durham North Carolina
United States Altru Health Systems Grand Forks North Dakota
United States Cancer and Hematology Centers of Western Michigan Grand Rapids Michigan
United States Baylor College of Medicine Houston Texas
United States Harris Health System - Smith Clinic Houston Texas
United States Lyndon B. Johnson Hospital Houston Texas
United States MD Anderson Cancer Center Houston Texas
United States Mayo Clinic - Jacksonville Jacksonville Florida
United States Saint Luke's Cancer Institute Kansas City Missouri
United States California Research Institute Los Angeles California
United States Norton Cancer Institute Louisville Kentucky
United States Miami Cancer Institute Miami Florida
United States Allina Health System DBA Virginia Piper Cancer Institute Minneapolis Minnesota
United States David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center New York New York
United States Icahn School of Medicine at Mount Sinai New York New York
United States Oklahoma University Health Sciences Center Oklahoma City Oklahoma
United States University of Nebraska Medical Center Omaha Nebraska
United States Mayo Clinic - Phoenix Phoenix Arizona
United States University of Pittsburgh Medical Center Pittsburgh Pennsylvania
United States Miami Cancer Institute Plantation Plantation Florida
United States Renown Regional Medical Centre Reno Nevada
United States Mayo Clinic - Rochester Rochester Minnesota
United States Washington University School of Medicine Saint Louis Missouri
United States Providence Medical Foundation - Santa Rosa, CA Santa Rosa California
United States University of Arizona - Cancer Center Tucson Arizona

Sponsors (1)

Lead Sponsor Collaborator
Sermonix Pharmaceuticals Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  France,  Germany,  Hungary,  Israel,  Italy,  Korea, Republic of,  Poland,  Romania,  Singapore,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Progression free survival (PFS) 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. Within approximately 3 years
Secondary Objective response rate (ORR) 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. Within approximately 3 years
Secondary Overall survival (OS) Overall survival is defined as time from the date of Visit 0 (Day 1) to death due to any cause. Within approximately 3 years
Secondary Clinical benefit rate (CBR) 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. Within approximately 3 years
Secondary Duration of response (DoR) in subjects with an objective response 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. Within approximately 3 years
Secondary Time to response (TTR) in subjects with an objective response TTR is from the date of randomization to the date of first documented confirmed response (CR or PR). Within approximately 3 years
Secondary Time to cytotoxic chemotherapy From the date of randomization to the date of first documented use of cytotoxic chemotherapy. Within approximately 3 years
Secondary Quality of Life (QoL) evaluated using the Functional Assessment of Cancer Therapy-Breast Cancer-Endocrine Subscale (FACT B-ES) Scale ranges from 'Not at all' to 'Very much' Within approximately 3 years
Secondary Incidence of Adverse Events (AEs) and Serious AEs 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 Within approximately 3 years
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