do_not_disturb_altRecruitment Complete

Vasomotor symptoms caused by adjuvant endocrine therapy in women with, or at high risk for developing hormone-receptor positive breast cancer, Hot flashes

A study to learn more about how well elinzanetant works and how safe it is compared to placebo for the treatment of hot flashes caused by anti-cancer therapy in women with, or at high risk for developing hormone-receptor positive breast cancer

Trial purpose

Researchers are looking for a better way to treat women with, or at high risk for developing hormone-receptor positive breast cancer, who have vasomotor symptoms (VMS), a condition of having hot flashes caused by anti-cancer therapy.
VMS, also called hot flashes, are very common medical problems in women with hormone-receptor (HR)-positive breast cancer, who are receiving anti-cancer therapy. HR-positive breast cancer is a type of breast cancer, which has hormone-receptors (proteins) for female sex hormones estrogen and/or progesterone. These hormone-receptors may attach to hormones like estrogen and progesterone and thereby help cancer cells to grow and to spread. Treatments that stop these hormones from attaching to these receptors are currently used to slow or stop the growth of HR-positive breast cancer.

It is already known that women with HR-positive breast cancer benefit from this treatment. However, hot flashes are common medical problems related to this therapy. They negatively affect quality of life of many women and may lead to discontinuation (stopping) of this therapy.
The study treatment, elinzanetant is being developed to treat hot flushes. It works by blocking a substance called neurokinin from sending signals to other parts of the body, which is thought to play a role in starting hot flashes.

The main purpose of this study is to learn more about how well elinzanetant helps to treat hot flashes caused by anti-cancer therapy in women with or at high risk for developing HR-positive breast cancer compared to placebo. A placebo is a treatment that looks like a medicine but does not have any medicine in it.
To answer this, the doctors will ask the participants to record information about their hot flashes before treatment start and at certain time points during the treatment in an electronic diary. The researchers will then assess possible average changes in number and severity of hot flashes after 4 and 12 weeks of treatment.

To see how safe elinzanetant is compared to placebo. The study will collect information about the number of participants who have medical problems after taking treatment.

The study participants will be randomly (by chance) assigned to 2 treatment groups, A and B. The participants from treatment group A will take elinzanetant. The participants from treatment group B will start with placebo and then switch to elinzanetant.

All participants will continue taking the anti-cancer therapy they have been using when entering the study.

Dependent on the treatment group, the participants will either take elinzanetant or placebo as capsules by mouth once a day. After 12 weeks, the participants who have initially received placebo will switch to take elinzanetant for the remaining 40 weeks.
Each participant will be in the study for approximately 62 weeks. The treatment duration in the study will be 52 weeks. There will be up to 12 visits to the study site and 6 phone calls in between. Participants who completed the 52 weeks treatment phase, will be offered to continue treatment for another 2 years. Visit frequency: every 24 weeks until week 152.

During the study, the participants will:
• record information about their hot flashes
• answer questions about their quality of life and other symptoms.
The doctors and their study team will:
• check the participants health and vital signs
• take blood and urine samples
• examine heart health using electrocardiogram (ECG)
• examine pelvic organs like womb or ovaries using a trans vaginal ultrasound scan to see images of these organs
• make images of the breast using x-ray (mammogram), a type of radiation that passes through the body to make images of the inside and/or by using ultrasound (if applicable)
• check the health of the participant’s cervix (neck of the womb) by taking a small sample of cells (smear test) for an analysis called cervical cytology (if applicable)
• take an endometrial biopsy, a small piece of tissue from the lining of the womb (called the endometrium) for analysis.
• ask the participants questions about what medicines they are taking and if they are having adverse events.

An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.
About 4 weeks after the participants take their last treatment, the study doctors and their team will check the participants’ health.

Key Participants Requirements

Sex

Female

Age

18 - 70 Years
  • - Females aged 18 to 70 years of age inclusive, at the time of signing the informed consent.
    - Women experiencing vasomotor symptoms (VMS) caused by adjuvant endocrine therapy that they are expected to use for the duration of the study
     -- Tamoxifen with or without the use of gonadotropin-releasing hormone (GnRH) analogues or
     -- Aromatase inhibitors with or without the use of GnRH analogues
    - Women must have
     -- a personal history of hormone-receptor positive breast cancer or
     -- a high risk for developing breast cancer.
    - Participant has completed Hot Flash Daily Diary (HFDD) for at least 11 days during the two weeks preceding baseline visit, and participant has recorded at least 35 moderate to severe hot flash (HF) (including night-time HF) over the last 7 days that the HFDD was completed (assessed at the Baseline Visit).
    - Contraceptive use by [women except for post-menopausal women or Women of Non childbearing potential (WONCBP)] should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • - Initial diagnosis of metastatic hormone-receptor positive breast cancer (stage IV) or recurrence under adjuvant endocrine therapy of hormone-receptor positive breast cancer.
    - Current or history (except complete remission for 5 years or more prior to signing informed consent) of any malignancy, except for hormone-receptor positive breast cancer (Stage 0-III), basal and squamous cell skin tumors.
    - Surgery or non-surgical (e.g., chemotherapy, radiotherapy, immunotherapy) treatment for breast cancer within the last 3 months prior to signing informed consent (except use of tamoxifen, aromatase inhibitors, GnRH analogues).
    - Any clinically significant prior or ongoing history of arrhythmias, heart block and QT prolongation either determined through clinical history or on electrocardiogram (ECG) evaluation.
    - Any active ongoing condition that could cause difficulty in interpreting VMS such as: infection that could cause pyrexia, pheochromocytoma, carcinoid syndrome.
    - Any unexplained vaginal bleeding.
    - Mammogram with clinically relevant malignant or suspicious findings that will require surgery, radiotherapy or chemotherapy as per local guidelines (mammogram should not be older than 12 months prior to signing informed consent). If a mammogram is not possible after partial mastectomy an ultrasound could be performed instead.
    - Disordered proliferative endometrium, endometrial hyperplasia, polyp, or endometrial cancer diagnosed based on endometrial biopsy during screening.
    - Current arterial or venous vascular event (e.g., Myocardial infarction (MI), Transient ischemic attack (TIA), stroke, deep vein thrombosis (DVT), i.e., within the last 6 months prior to signing informed consent.

Trial summary

Enrollment Goal
473
Trial Dates
October 2022 - December 2026
Phase
Phase 3
Could I Receive a placebo
Yes
Products
Elinzanetant (BAY3427080)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Active, not recruiting
Centro Hospitalar e Universitario de Coimbra, E.P.E. | Department of GynecologyCoimbra, 3000-075, Portugal
Active, not recruiting
Centro Clinico Academico Braga | Braga, PortugalBraga, 4710-243, Portugal
Active, not recruiting
Centro Hospitalar de Lisboa Ocidental | Clinical Research DepartmentLisboa, 1449-005, Portugal
Not yet recruiting
Centro Hospitalar Universitario do PortoPorto, 4050-651, Portugal
Active, not recruiting
Fundacao Champalimaud | Centro Clinico Champalimaud - Unidade Investigacao ClinicaLisboa, 1400-038, Portugal
Completed
Luz Saude | Hospital Beatriz Angelo - Centro de Investigacao ClinicaLoures, 2674-514, Portugal
Active, not recruiting
Luz Saude | Hospital da Luz Lisboa - Centro de Investigacao ClinicaLisboa, 1500-650, Portugal
Not yet recruiting
CHUSJ - Hospital Sao JoaoPorto, 4200-319, Portugal
Withdrawn
Barmhzg Schwestern | Brust-GesundheitszentrumLinz, 4010, Austria
Active, not recruiting
Medical University of Graz | Division of Gynecology and ObstetricsGraz, 8036, Austria
Active, not recruiting
Evangelisches Krankenhaus Bergisch Gladbach - GynäkologiBergisch Gladbach, 51465, Germany
Active, not recruiting
MedUni Innsbruck | Brust Gesundheit ZentrumInnsbruck, 6020, Austria
Active, not recruiting
Frauenarztpraxis Dr. Inka KiescheHalle, 6110, Germany
Active, not recruiting
Praxis f. Gynäkologie und GeburtshilfeBernburg, 6406, Germany
Withdrawn
H Univ. 12 de Octubre | Ginecología y ObstetriciaMadrid, 28041, Spain
Active, not recruiting
Virgen del Rocio University Hospital - Oncology DepartmentSevilla, 41013, Spain
Completed
Hospital General Universitario de ValenciaValencia, 46014, Spain
Active, not recruiting
Hospital Clínico Universitario de Santiago de CompostelaSantiago de Compostela, 15706, Spain
Active, not recruiting
Hospital Universitario Virgen de las Nieves | Oncologia MedicaGranada, 18014, Spain
Completed
Eberhard-Karls-Universität TübingenTübingen, 72076, Germany
Active, not recruiting
Praxisklinik am RosengartenMannheim, 68165, Germany
Active, not recruiting
Frauenärzte am Schloss BorbeckEssen, 45355, Germany
Active, not recruiting
Praxis Hr. Dr. S. FiedlerAachen, 52074, Germany
Active, not recruiting
Hospital del MarBarcelona, 08003, Spain
Active, not recruiting
Hospital General Universitario Gregorio Maranon | OncologiaMadrid, 28009, Spain
Active, not recruiting
Hospital Universitario La Zarzuela | Clinical Research UnitAravaca, 28023, Spain
Active, not recruiting
Rub-Int Noi EgeszsegcentrumSzekesfehervar, 8000, Hungary
Active, not recruiting
Axon Kft.Kecskemet, 6000, Hungary
Active, not recruiting
AKH Wien | Allg. Gynaekologie & gynaekologische OnkologieWien, 1090, Austria
Completed
Debreceni Egyetem Klinikai KozpontDebrecen, 4032, Hungary
Active, not recruiting
Szabolcs Szatmr Bereg County University Teaching Hospital | Andras Jasa Teaching Hospital - OncologyNyiregyhaza, 4400, Hungary
Completed
Institut Bergonié - Unicancer Nouvelle AquitaineBORDEAUX CEDEX, 33076, France
Active, not recruiting
Institut de Cancérologie de l'Ouest - Saint HerblainSaint-Herblain, 44800, France
Active, not recruiting
Centre de Lutte Contre le Cancer François BaclesseCAEN CEDEX 5, 14076, France
Active, not recruiting
ICO Site Paul Papin - AngersANGERS, 49055, France
Active, not recruiting
Centrum Medyczne Pratia PoznanSkorzewo, 60-185, Poland
Completed
Salve Medica Sp. z o.o. SP.K.Lodz, 91-211, Poland
Active, not recruiting
NZOZ MEDEM Wilk Sp. j.Katowice, 40-301, Poland
Active, not recruiting
PRATIA MCM KRAKÓWKrakow, 30-727, Poland
Active, not recruiting
CLINICAL MEDICAL RESEARCH Sp. z o. o.Katowice, 40-156, Poland
Active, not recruiting
Prywatny Gabinet Lekarski Ginekologia, Poloznictwo i Ultr.Lodz, 90-602, Poland
Active, not recruiting
Gabinet Ginekologiczny Janusz TomaszewskiBialystok, 15-224, Poland
Active, not recruiting
Gynäkologisches Zentrum BonnBonn, 53111, Germany
Withdrawn
Uniklinik Ulm / Klinik für Frauenheilkunde und GeburtshilfeUlm, 89075, Germany
Active, not recruiting
Medplus NordrheinKrefeld, 47799, Germany
Active, not recruiting
Centre Leon Berardlyon, 69008, France
Active, not recruiting
ICANS - Institut de Cancérologie de Strasbourg EuropeSTRASBOURG, 67033, France
Active, not recruiting
Azienda Ospedaliera Universitaria Integrata Verona_Borgo Trento - Ostetricia e Ginecologia BVerona, 37126, Italy
Active, not recruiting
IRCCS Fondazione Policlinico San MatteoPavia, 27100, Italy
Active, not recruiting
Istituto Europeo di Oncologia s.r.l - Ginecologia PreventivaMilano, 20141, Italy
Active, not recruiting
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Ginecologia OncologicaRoma, 00168, Italy
Active, not recruiting
IRCCS Ospedale Policlinico San Martino - Clinica ostetrica e ginecologicaGenova, 16132, Italy
Active, not recruiting
Health Corporation of Galilee Medical CenterNahariya, 2210001, Israel
Active, not recruiting
Meir Medical CenterKfar Saba, 4428164, Israel
Active, not recruiting
Chaim Sheba Medical CenterRamat Gan, 5266202, Israel
Active, not recruiting
Hadassah Hebrew University Hospital Ein KeremJerusalem, 9112001, Israel
Completed
S.C. Quantum Medical Center SRLBucuresti, 012071, Romania
Completed
Spitalul Clinic FilantropiaBucuresti, 11132, Romania
Not yet recruiting
CHULN - H. Sta.Maria (Centro de Investigacao Clinica)Lisboa, 1649-035, Portugal
Active, not recruiting
Companhia Uniao Fabril | Hospital CUF Porto - Clinical Trials DepartmentPorto, 4100-180, Portugal
Active, not recruiting
Institut du Cancer de Montpellier - Val d'AurelleMONTPELLIER CEDEX, 34298, France
Completed
Hôpital Saint LouisPARIS, 75010, France
Active, not recruiting
A.O. Ordine MaurizianoTorino, 10128, Italy
Withdrawn
Sf. Nectarie Oncology CenterCraiova, 200542, Romania
Active, not recruiting
SC ONCOLAB SRLCraiova, 200385, Romania
Active, not recruiting
Docrates KlinikkaHelsinki, 00180, Finland
Active, not recruiting
Tampereen yliopistollinen sairaalaTampere, 33520, Finland
Active, not recruiting
Vaasan keskussairaalaVaasa, 65130, Finland
Active, not recruiting
Mehilainen | Mehilainen KuopioKuopio, 70100, Finland
Active, not recruiting
Lääkärikeskus Gyneko, Gynaecological Medical Center | Oulu, FinlandOulu, 90100, Finland
Active, not recruiting
A.O.U. di Modena - PoliclinicoModena, 41100, Italy
Withdrawn
OncocenterTimisoara, 300166, Romania
Active, not recruiting
Hôpital TenonPARIS, 75020, France
Active, not recruiting
Liverpool Women's NHS Foundation Trust | Liverpool Women's Hospital | GynaecologyLiverpool, L8 7SS, United Kingdom
Active, not recruiting
Imperial College Healthcare NHS Trust| Queen Charlotte's and Chelsea Hospital - GynaecologyLondon, W12 0NN, United Kingdom
Active, not recruiting
NHS Greater Glasgow and Clyde | Glasgow Royal Infirmary - GynaecologyGlasgow, G4 0SF, United Kingdom
Active, not recruiting
Surrey and Sussex Healthcare NHS TrustRedhill, RH1 5RH, United Kingdom
Active, not recruiting
Aberdeen Royal InfirmaryAberdeen, AB25 2ZN, United Kingdom
Active, not recruiting
Tel-Aviv Sourasky Medical CenterTel-Aviv-Jaffa, 6492601, Israel
Active, not recruiting
Assuta Ashdod Public Hospital (R.A)Ashdod, 7747629, Israel
Active, not recruiting
University College Hospital GalwayGalway, H91YR71, Ireland
Active, not recruiting
Mater Misericordiae University HospitalDublin, D07R2WY, Ireland
Active, not recruiting
St Vincents University HospitalDublin 4, TBC, Ireland
Active, not recruiting
St James' HospitalDublin, D08NHY1, Ireland
Not yet recruiting
Cork University HospitalCork, T12DC4A, Ireland
Active, not recruiting
S.C Ovidius Clinical Hospital SRL - Oncology DepartmentOvidiu, 905900, Romania
Withdrawn
Spitalul Municipal PloiestiPloiesti, 100337, Romania
Active, not recruiting
Ghent University Hospital | Women's Clinic DepartmentGent, 9000, Belgium
Active, not recruiting
UZ Leuven GasthuisbergLEUVEN, 3000, Belgium
Active, not recruiting
Hôpital Erasme/Erasmus ZiekenhuisBrussels, 1070, Belgium
Active, not recruiting
CHU Saint-Pierre/UMC Sint-PieterBRUXELLES - BRUSSEL, 1000, Belgium
Completed
CU Saint-Luc/UZ St-LucBRUXELLES - BRUSSEL, 1200, Belgium
Active, not recruiting
Femicare vzw | Tienen, BETienen, 3300, Belgium
Active, not recruiting
ZAS Augustinus - Gynaecology departmentWilrijk, 2610, Belgium
Completed
Kazakh Institute of Oncology and Radiology - Department of GynecologyAlmaty, 640000, Kazakhstan
Completed
Multidisciplinary Medical Center of the Akimat of Astana - Department of Chemotherapy No1Astana, 010000, Kazakhstan
Completed
Centrum Badawcze Wspolczesnej TerapiiWarszawa, 02-679, Poland
Withdrawn
Hamilton Health Sciences-Juravinski Cancer CentreHamilton, L8V 5C2, Canada
Active, not recruiting
Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM)Montreal, H2X 0A9, Canada
Withdrawn
Women's College HospitalToronto, M5S 1B2, Canada
Completed
Careggi University Hospital - Ostetricia e GinecologiaFirenze, 50134, Italy
Active, not recruiting
Azienda Ospedaliera Universitaria Federico II Di Napoli - DAI Materno InfantileNapoli, 80131, Italy
Active, not recruiting
The Ottawa Hospital - Riverside CampusOttawa, K1H 7W9, Canada
Active, not recruiting
Ziekenhuis Oost-Limburg - Gynecology DepartmentGenk, 3600, Belgium
Active, not recruiting
Synexus Frankfurt Clinical Research CentreFrankfurt, 60313, Germany
Withdrawn
Hospital Universitario La Paz | Ginecology DepartmentMadirid, 28046, Spain
Terminated
Hospital Clinico Universitario | Gynecology and Obstetrics DepartmentValencia, 46010, Spain
Completed
S.C. Centrul Medical de Diagnostic si Tratament Ambulator Neomed SRLBrasov, 500283, Romania
Active, not recruiting
Klinische Forschung Hannover-Mitte GmbHHannover, 30159, Germany
Active, not recruiting
University Hospital WaterfordWaterford, X91 ER8E, Ireland
Completed
Klinische Forschung Berlin-Mitte GmbHBerlin, 10117, Germany

Primary Outcome

  • Mean change in frequency of moderate to severe hot flash (HF) from baseline to Week 4 (assessed by hot flash daily diary [HFDD])
    date_rangeTime Frame:
    Baseline to Week 4
  • Mean change in frequency of moderate to severe HF from baseline to Week 12 (assessed by HFDD)
    date_rangeTime Frame:
    Baseline to Week 12

Secondary Outcome

  • Mean change in severity of moderate to severe HF from baseline to Week 4 (assessed by HFDD).
    date_rangeTime Frame:
    Baseline to Week 4
  • Mean change in severity of moderate to severe HF from baseline to Week 12 (assessed by HFDD)
    date_rangeTime Frame:
    Baseline to Week 12
  • Mean change in frequency of moderate to severe HF from baseline to Week 1 (assessed by HFDD)
    date_rangeTime Frame:
    Baseline to Week 1
  • Mean change in frequency of moderate to severe HF from baseline over time (assessed by HFDD)
    date_rangeTime Frame:
    Baseline to Week 52
  • Mean change in patient-reported outcomes measurement information system sleep disturbance short form 8b (PROMIS SD SF 8b) total score from baseline to Week 12
    The PROMIS SD SF 8b includes 8 items assessing sleep disturbance over the past 7 days. Items assess sleep quality, sleep depth and restoration associated with sleep, perceived difficulties with getting to sleep or staying asleep and perceptions of the adequacy of and satisfaction with sleep. Participants respond to the items on a 5-point scale from not at all, never or very poor to very much, always or very good. Four of the items are scored reversely. Total scores range from 8 to 40, with higher scores indicating greater severity of sleep disturbance
    date_rangeTime Frame:
    Baseline to Week 12
  • Mean change in menopause specific quality of life scale (MENQOL) total score from baseline to Week 12
    The MENQOL questionnaire is comprised of 29 items assessing the presence of menopausal symptoms and the impact of menopause on health-related quality of life over the past week. The items assess four domains of symptoms and functioning: VMS, psychosocial functioning, physical functioning, and sexual functioning. For each item, the participant indicates if they have experienced the symptom (yes/no). If participants select yes, participants rate how bothered they were by the symptom using a six-point verbal descriptor scale, with response options ranging from 0 'not at all bothered' to 6 'extremely bothered'. Based on the individual responses, item scores, domain scores, and a total MENQOL score are calculated. Each score ranges from 1-8, higher scores indicate greater bother.
    date_rangeTime Frame:
    Baseline to Week 12

Trial design

A double-blind, randomized, placebo-controlled multicenter study to investigate efficacy and safety of elinzanetant for the treatment of vasomotor symptoms induced by adjuvant endocrine therapy, over 52 weeks and optionally for additional 2 years in women with hormone-receptor positive breast cancer:
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
N/A
Assignment
Parallel Assignment
Trial Arms
2