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 (OASIS-4)

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:

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hot Flashes; Vasomotor Symptoms Caused by Adjuvant Endocrine Therapy in Women With, or at High Risk for Developing Hormone-receptor Positive Breast Cancer
• Intervention / Treatment: Drug: Elinzanetant (BAY3427080); Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 473
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Bayer Clinical Trials Contact; Phone Number: (+)1-888-84 22937; Email: clinical-trials-contact@bayer.com

Study Locations

• Austria
  • Wien, Austria, 1090
    • AKH Wien | Allg. Gynaekologie & gynaekologische Onkologie
  • Steiermark
    • Graz, Steiermark, Austria, 8036
      • Medizinische Univ Graz | Frauenheilkunde & Geburtshilfe
  • Tirol
    • Innsbruck, Tirol, Austria, 6020
      • MedUni Innsbruck | Brust Gesundheit Zentrum
• Belgium
  • Brussels, Belgium, 1070
    • Hôpital Erasme/Erasmus Ziekenhuis
  • Bruxelles - Brussel, Belgium, 1200
    • CU Saint-Luc/UZ St-Luc
  • Bruxelles - Brussel, Belgium, 1000
    • CHU Saint-Pierre/UMC Sint-Pieter
  • Genk, Belgium, 3600
    • Ziekenhuis Oost-Limburg - Gynecology Department
  • Gent, Belgium, 9000
    • Ghent University Hospital | Women's Clinic Department
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Tienen, Belgium, 3300
    • Femicare vzw
  • Antwerpen
    • Wilrijk, Antwerpen, Belgium, 2610
      • GZA Ziekenhuizen
• Canada
  • Ottawa, Canada, K1H 7W9
    • The Ottawa Hospital - Riverside Campus
  • Quebec
    • Montreal, Quebec, Canada, H2X 0A9
      • Centre de Recherche du Centre Hospitalier de l'Université de Montreal (CRCHUM)
• Finland
  • Helsinki, Finland, 00180
    • Docrates Klinikka
  • Kuopio, Finland, 70100
    • Mehiläinen Kuopio
  • Oulu, Finland, 90100
    • Lääkärikeskus Gyneko
  • Tampere, Finland, 33521
    • Tampereen yliopistollinen sairaala, keskussairaala
  • Vaasa, Finland, 65130
    • Vaasan Keskussairaala
• France
  • Angers, France, 49055
    • ICO Site Paul Papin - Angers
  • Bordeaux, France, 33076
    • Institut Bergonié - Unicancer Nouvelle Aquitaine
  • Caen Cedex 5, France, 14076
    • Centre de Lutte Contre Le Cancer Francois Baclesse
  • Lyon, France, 69008
    • Centre Léon Bérard
  • Montpellier Cedex, France, 34298
    • Institut du Cancer de Montpellier - Val d'Aurelle
  • Paris, France, 75010
    • Hopital Saint Louis
  • Paris, France, 75020
    • Hôpital Tenon
  • Saint-Herblain, France, 44800
    • Institut de Cancérologie de l'Ouest - Saint Herblain
  • Strasbourg, France, 67033
    • ICANS - Institut de Cancérologie de Strasbourg Europe
• Germany
  • Berlin, Germany, 10117
    • Klinische Forschung Berlin-Mitte GmbH
  • Baden-Württemberg
    • Mannheim, Baden-Württemberg, Germany, 68165
      • Praxisklinik am Rosengarten
    • Tübingen, Baden-Württemberg, Germany, 72076
      • Eberhard-Karls-Universität Tübingen
  • Hessen
    • Frankfurt, Hessen, Germany, 60313
      • Synexus Frankfurt Clinical Research Centre
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30159
      • Klinische Forschung Hannover-Mitte GmbH
  • Nordrhein-Westfalen
    • Aachen, Nordrhein-Westfalen, Germany, 52074
      • Praxis Hr. Dr. S. Fiedler
    • Bergisch Gladbach, Nordrhein-Westfalen, Germany, 51465
      • Evangelisches Krankenhaus Bergisch Gladbach
    • Bonn, Nordrhein-Westfalen, Germany, 53111
      • Gynäkologisches Zentrum
    • Essen, Nordrhein-Westfalen, Germany, 45355
      • Frauenärzte am Schloss Borbeck
    • Krefeld, Nordrhein-Westfalen, Germany, 47799
      • Medplus Nordrhein
  • Sachsen-Anhalt
    • Bernburg, Sachsen-Anhalt, Germany, 06406
      • Praxis f. Gynäkologie und Geburtshilfe
    • Halle, Sachsen-Anhalt, Germany, 06110
      • Frauenarztpraxis Dr. Inka Kiesche
• Hungary
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Kozpont
  • Kecskemet, Hungary, 6000
    • Axon Kft.
  • Nyiregyhaza, Hungary, 4400
    • SzSzBMK es EOK Josa Andras Oktatokorhaz
  • Szekesfehervar, Hungary, 8000
    • Rub-Int Noi Egeszsegcentrum
• Ireland
  • Dublin, Ireland, 7
    • Mater Misericordiae University Hospital
  • Dublin, Ireland, D04T6F4
    • St Vincents University Hospital
  • Dublin, Ireland, D08NHY1
    • St James' Hospital
  • Galway, Ireland, H91YR71
    • University College Hospital Galway
  • Waterford, Ireland, X91ER8E
    • University Hospital Waterford
• Israel
  • Ashdod, Israel, 7747629
    • Assuta Ashdod
  • Jerusalem, Israel, 9112001
    • Hadassah Hebrew University Hospital Ein Kerem
  • Kfar Saba, Israel, 4428164
    • Meir Medical Center
  • Nahariya, Israel, 2210001
    • Health Corporation of Galilee Medical Center
  • Ramat Gan, Israel, 5262000
    • Chaim Sheba Medical Center
  • Tel Aviv, Israel, 6423906
    • Tel-Aviv Sourasky Medical Center
• Italy
  • Campania
    • Naples, Campania, Italy, 80131
      • A.O.U. Policlinico Federico II Napoli
  • Emilia-Romagna
    • Modena, Emilia-Romagna, Italy, 41124
      • A.O.U. di Modena - Policlinico
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Fondazione Policlinico Universitario Agostino Gemelli IRCCS
  • Liguria
    • Genova, Liguria, Italy, 16132
      • IRCCS Ospedale Policlinico San Martino
  • Lombardia
    • Milano, Lombardia, Italy, 20141
      • IRCCS Istituto Europeo di Oncologia s.r.l. (IEO)
    • Pavia, Lombardia, Italy, 27100
      • Fondazione IRCCS Policlinico San Matteo
  • Piemonte
    • Torino, Piemonte, Italy, 10128
      • A.O. Ordine Mauriziano
  • Toscana
    • Firenze, Toscana, Italy, 50134
      • A.O.U. Careggi
  • Veneto
    • Verona, Veneto, Italy, 37126
      • A.O.U.I. Verona
• Kazakhstan
  • Almaty, Kazakhstan, 50000
    • Kaz. Inst. of oncology and radiology | Dept. of gynecology
  • Nur-Sultan, Kazakhstan, 010009
    • Multifield medical center | Chemotherapy department No 1
• Poland
  • Bialystok, Poland, 15-244
    • Gabinet Ginekologiczny Janusz Tomaszewski
  • Katowice, Poland, 40-156
    • CLINICAL MEDICAL RESEARCH Sp. z o. o.
  • Katowice, Poland, 40-301
    • NZOZ MEDEM Wilk Sp. j.
  • Krakow, Poland, 30-510
    • Pratia S.A
  • Lodz, Poland, 90-602
    • Prywatny Gabinet Lekarski Ginekologia, Poloznictwo i Ultr.
  • Lodz, Poland, 91-211
    • Salve Medica Sp. z o.o. SP.K.
  • Skorzewo, Poland, 60-185
    • Pratia S.A
  • Warszawa, Poland, 02-679
    • Centrum Badawcze Wspolczesnej Terapii
• Portugal
  • Braga, Portugal, 4710-243
    • Centro Clinico Academico Braga | Braga, Portugal
  • Coimbra, Portugal, 3004-561
    • CHUC - Hospitais da U. Coimbra - Servico de Ginecologia
  • Lisboa, Portugal, 1449-005
    • Centro Hospitalar de Lisboa Ocidental | Clin Res Dept
  • Lisboa, Portugal, 1649-035
    • CHULN - H. Sta.Maria (Centro de Investigacao Clinica)
  • Lisboa, Portugal, 1500-650
    • Luz Saude | Hospital da Luz Lisboa - Centro de Investigacao Clinica
  • Lisboa, Portugal, 1400-038
    • Fundacao Champalimaud | Centro Clinico Champalimaud - Unidade Investigacao Clinica
  • Porto, Portugal, 4200-319
    • CHUSJ - Hospital Sao Joao
  • Porto, Portugal, 4050-651
    • Centro Hospitalar Universitario do Porto
  • Porto, Portugal, 4100-180
    • Companhia Uniao Fabril | Hospital CUF Porto - Clinical Trials Department
  • Lisboa
    • Loures, Lisboa, Portugal, 2674-514
      • Luz Saude | Hospital Beatriz Angelo - Centro de Investigacao Clinica
• Romania
  • Brasov, Romania, 500283
    • S.C. Centrul Medical de Diagn si Tratam Ambulator Neomed SRL
  • Bucuresti, Romania, 012071
    • S.C. Quantum Medical Center S.R.L
  • Bucuresti, Romania, 11132
    • Spitalul Clinic Filantropia
  • Craiova, Romania, 200385
    • Sc Oncolab Srl
  • Ovidiu, Romania, 905900
    • S.C Ovidius Clinical Hospital SRL - Oncology Department
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Granada, Spain, 18014
    • Hospital Universitario Virgen de las Nieves|Oncologia
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Maranon | Oncologia
  • Sevilla, Spain, 41013
    • Virgen del Rocio University Hospital - Oncology Department
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15706
      • Hospital Clinico Universitario de Santiago de Compostela
  • Madrid
    • Aravaca, Madrid, Spain, 28023
      • Hospital Sanitas La Zarzuela
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
    • Aberdeen Royal Infirmary
  • Glasgow, United Kingdom, G4 0SF
    • Glasgow Royal Infirmary | Haematology
  • Liverpool, United Kingdom, L8 7SS
    • Liverpool Womens Hospital
  • London, United Kingdom, W12 0NN
    • Queen Charlottes & Chelseas Hospital
  • Surrey
    • Redhill, Surrey, United Kingdom, RH1 5RH
      • Surrey and Sussex Healthcare NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive matching placebo orally once daily.	Drug: Placebo; Matching placebo orally once daily.
Experimental: Elinzanetant (BAY3427080); Participants will receive 120 mg elinzanetant orally once daily.	Drug: Elinzanetant (BAY3427080); 120 mg elinzanetant orally once daily

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change in severity of moderate to severe HF from baseline to Week 12 (assessed by HFDD)		Baseline to Week 12
Mean change in frequency of moderate to severe HF from baseline to Week 1 (assessed by HFDD)		Baseline to Week 1
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.	Baseline to Week 12
Mean change in severity of moderate to severe HF from baseline to Week 4 (assessed by HFDD).		Baseline to Week 4
Mean change in frequency of moderate to severe HF from baseline over time (assessed by HFDD)		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	Baseline to Week 12

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): October 14, 2022
• Primary Completion (Actual): January 29, 2024
• Study Completion (Estimated): December 4, 2026

Study Registration Dates

• First Submitted: October 17, 2022
• First Submitted That Met QC Criteria: October 17, 2022
• First Posted (Actual): October 20, 2022

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Hot Flashes
• Other Study ID Numbers: 21656; 2022-000095-18 (EudraCT Number); 2023-508265-33-00 (Registry Identifier: CTIS (EU))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes