Clinical trial NCT05587296: 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
Official title: 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:
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Vasomotor Symptoms Caused by Adjuvant Endocrine Therapy in Women With, or at High Risk for Developing Hormone-receptor Positive Breast Cancer
Hot Flashes
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2022-10-20
Enrollment: 473
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Mean change in frequency of moderate to severe hot flash (HF) from baseline to Week 4 (assessed by hot flash daily diary [HFDD])
timeFrame: Baseline to Week 4
measure: Mean change in frequency of moderate to severe HF from baseline to Week 12 (assessed by HFDD)
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Mean change in severity of moderate to severe HF from baseline to Week 4 (assessed by HFDD).
timeFrame: Baseline to Week 4
measure: Mean change in severity of moderate to severe HF from baseline to Week 12 (assessed by HFDD)
timeFrame: Baseline to Week 12
measure: Mean change in frequency of moderate to severe HF from baseline to Week 1 (assessed by HFDD)
timeFrame: Baseline to Week 1
measure: Mean change in frequency of moderate to severe HF from baseline over time (assessed by HFDD)
timeFrame: Baseline to Week 52
measure: 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
timeFrame: Baseline to Week 12
measure: Mean change in menopause specific quality of life scale (MENQOL) total score from baseline to Week 12
timeFrame: Baseline to Week 12
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medical University of Graz | Division of Gynecology and Obstetrics
state: Steiermark
city: Innsbruck
country: Austria
facility: MedUni Innsbruck | Brust Gesundheit Zentrum
state: Tirol
city: Wien
country: Austria
facility: AKH Wien | Allg. Gynaekologie & gynaekologische Onkologie
city: Wilrijk
country: Belgium
facility: ZAS Augustinus - Gynaecology department
state: Antwerpen
city: Brussels
country: Belgium
facility: Hôpital Erasme/Erasmus Ziekenhuis
city: Bruxelles - Brussel
country: Belgium
facility: CHU Saint-Pierre/UMC Sint-Pieter
city: Bruxelles - Brussel
country: Belgium
facility: CU Saint-Luc/UZ St-Luc
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg - Gynecology Department
city: Gent
country: Belgium
facility: Ghent University Hospital | Women's Clinic Department
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Tienen
country: Belgium
facility: Femicare vzw | Tienen, BE
city: Ottawa
country: Canada
facility: The Ottawa Hospital - Riverside Campus
state: Ontario
city: Montreal
country: Canada
facility: Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM)
state: Quebec
city: Helsinki
country: Finland
facility: Docrates Klinikka
city: Kuopio
country: Finland
facility: Mehilainen | Mehilainen Kuopio
city: Oulu
country: Finland
facility: Lääkärikeskus Gyneko, Gynaecological Medical Center | Oulu, Finland
city: Tampere
country: Finland
facility: Tampereen yliopistollinen sairaala
city: Vaasa
country: Finland
facility: Vaasan keskussairaala
city: Angers
country: France
facility: ICO Site Paul Papin - Angers - Service Oncologie
city: Bordeaux Cedex
country: France
facility: Institut Bergonie - Unicancer Nouvelle Aquitaine
city: Caen Cedex 5
country: France
facility: Centre de Lutte Contre le Cancer François Baclesse - Service Pathologie mammaire
city: Lyon
country: France
facility: UNICANCER - Centre Leon Berard (CLB)
city: Montpellier Cedex
country: France
facility: ICM - Institut du Cancer de Montpellier - Val d'Aurelle
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Assistance Publique-Hopitaux de Paris (AP-HP) - Hopital Tenon
city: Saint-Herblain
country: France
facility: Institut de Cancerologie Ouest - Saint-Herblain - Service gynecologie medicale
city: Strasbourg
country: France
facility: ICANS - Institut de Cancerologie de Strasbourg Europe
city: Mannheim
country: Germany
facility: Praxisklinik am Rosengarten
state: Baden-Württemberg
city: Tübingen
country: Germany
facility: Eberhard-Karls-Universität Tübingen
state: Baden-Württemberg
city: Frankfurt
country: Germany
facility: Synexus Frankfurt Clinical Research Centre
state: Hessen
city: Hannover
country: Germany
facility: Klinische Forschung Hannover-Mitte GmbH
state: Niedersachsen
city: Aachen
country: Germany
facility: Praxis Hr. Dr. S. Fiedler
state: Nordrhein-Westfalen
city: Bergisch Gladbach
country: Germany
facility: Evangelisches Krankenhaus Bergisch Gladbach - Gynäkologi
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: Gynäkologisches Zentrum Bonn
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: Frauenärzte am Schloss Borbeck
state: Nordrhein-Westfalen
city: Krefeld
country: Germany
facility: Medplus Nordrhein
state: Nordrhein-Westfalen
city: Bernburg
country: Germany
facility: Praxis f. Gynäkologie und Geburtshilfe
state: Sachsen-Anhalt
city: Halle
country: Germany
facility: Frauenarztpraxis Dr. Inka Kiesche
state: Sachsen-Anhalt
city: Berlin
country: Germany
facility: Klinische Forschung Berlin-Mitte GmbH
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Kecskemet
country: Hungary
facility: Axon Kft.
city: Nyiregyhaza
country: Hungary
facility: Szabolcs Szatmr Bereg County University Teaching Hospital | Andras Jasa Teaching Hospital - Oncology
city: Szekesfehervar
country: Hungary
facility: Rub-Int Noi Egeszsegcentrum
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin 4
country: Ireland
facility: St Vincents University Hospital
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Dublin
country: Ireland
facility: St James' Hospital
city: Galway
country: Ireland
facility: University College Hospital Galway
city: Waterford
country: Ireland
facility: University Hospital Waterford
city: Ashdod
country: Israel
facility: Assuta Ashdod Public Hospital (R.A)
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Hospital Ein Kerem
city: Kfar Saba
country: Israel
facility: Meir Medical Center
city: Nahariya
country: Israel
facility: Health Corporation of Galilee Medical Center
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tel-Aviv-Jaffa
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II Di Napoli - DAI Materno Infantile
state: Campania
city: Modena
country: Italy
facility: Azienda Ospedaliero Universitaria di Modena_Policlinico - Oncologia
state: Emilia-Romagna
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Agostino Gemelli IRCCS - UOC Ginecologia Oncologica
state: Lazio
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino - Clinica ostetrica e ginecologica
state: Liguria
city: Milano
country: Italy
facility: Istituto Europeo di Oncologia s.r.l - Ginecologia Preventiva
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo - Ostetricia e Ginecologia
state: Lombardia
city: Torino
country: Italy
facility: Azienda Ospedaliera Ordine Mauriziano Di Torino - Ostetricia e Ginecologia
state: Piemonte
city: Firenze
country: Italy
facility: Careggi University Hospital - Ostetricia e Ginecologia
state: Toscana
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona_Borgo Trento - Ostetricia e Ginecologia B
state: Veneto
city: Almaty
country: Kazakhstan
facility: Kazakh Institute of Oncology and Radiology - Department of Gynecology
city: Astana
country: Kazakhstan
facility: Multidisciplinary Medical Center of the Akimat of Astana - Department of Chemotherapy No1
city: Bialystok
country: Poland
facility: Gabinet Ginekologiczny Janusz Tomaszewski
city: Katowice
country: Poland
facility: CLINICAL MEDICAL RESEARCH Sp. z o. o.
city: Katowice
country: Poland
facility: NZOZ MEDEM Wilk Sp. j.
city: Krakow
country: Poland
facility: Pratia McM Kraków
city: Lodz
country: Poland
facility: Prywatny Gabinet Lekarski Ginekologia, Poloznictwo i Ultr.
city: Lodz
country: Poland
facility: Salve Medica Sp. z o.o. SP.K.
city: Skorzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan
city: Warszawa
country: Poland
facility: Centrum Badawcze Wspolczesnej Terapii
city: Loures
country: Portugal
facility: Luz Saude | Hospital Beatriz Angelo - Centro de Investigacao Clinica
state: Lisboa
city: Braga
country: Portugal
facility: Centro Clinico Academico Braga | Braga, Portugal
city: Coimbra
country: Portugal
facility: Centro Hospitalar e Universitario de Coimbra, E.P.E. | Department of Gynecology
city: Lisboa
country: Portugal
facility: Fundacao Champalimaud | Centro Clinico Champalimaud - Unidade Investigacao Clinica
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Ocidental | Clinical Research Department
city: Lisboa
country: Portugal
facility: Luz Saude | Hospital da Luz Lisboa - Centro de Investigacao Clinica
city: Lisboa
country: Portugal
facility: CHULN - H. Sta.Maria (Centro de Investigacao Clinica)
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario do Porto
city: Porto
country: Portugal
facility: Companhia Uniao Fabril | Hospital CUF Porto - Clinical Trials Department
city: Porto
country: Portugal
facility: CHUSJ - Hospital Sao Joao
city: Craiova
country: Romania
facility: Sc Oncolab Srl
state: Dolj
city: Brasov
country: Romania
facility: S.C. Centrul Medical de Diagnostic si Tratament Ambulator Neomed SRL
city: Bucuresti
country: Romania
facility: S.C. Quantum Medical Center SRL
city: Bucuresti
country: Romania
facility: Spitalul Clinic Filantropia
city: Ovidiu
country: Romania
facility: S.C Ovidius Clinical Hospital SRL - Oncology Department
city: Santiago de Compostela
country: Spain
facility: Hospital Clínico Universitario de Santiago de Compostela
state: A Coruña
city: Aravaca
country: Spain
facility: Hospital Universitario La Zarzuela | Clinical Research Unit
state: Madrid
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves | Oncologia Medica
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon | Oncologia
city: Sevilla
country: Spain
facility: Virgen del Rocio University Hospital - Oncology Department
city: Valencia
country: Spain
facility: Hospital Clinico Universitario | Gynecology and Obstetrics Department
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
city: Redhill
country: United Kingdom
facility: Surrey and Sussex Healthcare NHS Trust - East Surrey Hospital - Gynaecology
state: Surrey
city: Aberdeen
country: United Kingdom
facility: NHS Grampian | Aberdeen Royal Infirmary - Gynaecology
city: Glasgow
country: United Kingdom
facility: NHS Greater Glasgow and Clyde | Glasgow Royal Infirmary - Gynaecology
city: Liverpool
country: United Kingdom
facility: Liverpool Women's NHS Foundation Trust | Liverpool Women's Hospital - Gynaecology
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust| Queen Charlotte's and Chelsea Hospital - Gynaecology
Study officials:
References: