Clinical trial NCT06440967: A Study to Confirm if Fezolinetant Helps Reduce Hot Flashes in Women With Breast Cancer Who Are Having Hormone Therapy
Official title: A Randomized, Placebo-controlled, Double-blind, Phase 3 Clinical Study to Investigate the Efficacy and Safety of Fezolinetant for Treatment of Moderate to Severe Vasomotor Symptoms (Hot Flashes) in Women With Stage 0 to 3 Hormone Receptor-positive Breast Cancer Who Are Receiving Adjuvant Endocrine Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hot Flashes
Keywords: ESN364;
vasomotor symptoms;
fezolinetant;
VEOZAH™
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2024-06-04
Enrollment: 540
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: One of the standard treatments for women with breast cancer is hormone therapy, but this treatment can cause hot flashes. Hormone replacement therapy, or HRT, is most often prescribed for hot flashes for women in menopause but cannot be given to women on hormone therapy for breast cancer. Fezolinetant, an alternative to HRT, treats hot flashes for women in menopause. As hot flashes happen in the same way for women on hormone therapy for breast cancer, fezolinetant could help these women. In this study, women on hormone therapy for breast cancer who have moderate to severe hot flashes will take part. They will either take fezolinetant or a placebo to treat their hot flashes. The placebo looks like fezolinetant but doesn't have any medicine in it.

The main aim of this study is to confirm if women who take fezolinetant have fewer hot flashes that are less severe compared to women who take the placebo.

Women 18 years or older seeking treatment for hot flashes. They can take part in the study if they have an average of 7 or more moderate to severe hot flashes each day. They are having hormone therapy for breast cancer from stage 0 (cancer cells that have not spread to nearby tissue) up to stage 3+ (the cancer has spread from the breast to the lymph nodes near the breast or the chest wall).

The women will be assigned 1 of 2 study treatments (fezolinetant or placebo) by chance alone. Treatment will be double-blinded. That means that the women in the study and the study doctors will not know who takes which of the study treatments (fezolinetant or placebo). Women who take part in the study will take 1 tablet every day for 52 weeks (1 year). Each woman will be given an electronic handheld device with an app to track their hot flashes on a daily basis. Some women may be able to use the app on their own smartphone. They will also use another device to answer questions about how hot flashes affect their daily life. During the study, the women will visit their study clinic about every 4 weeks for a health check. The last clinic visit will be 3 weeks after the women take their last tablet of study treatment (fezolinetant or placebo). After this visit the women will be called twice to check their health. The women will be in the study for about 2 years.


Eligibility criteria: Inclusion Criteria:

* Participant has a personal history of stage 0-3 hormone receptor positive (HR+), either human epidermal growth factor receptor (HER)-2+ or HER-2- breast cancer; appropriate documentation includes a written or electronic report.
* Participant must be receiving stable maintenance adjuvant endocrine therapy (tamoxifen 20 mg daily or aromatase inhibitors, such as anastrozole, letrozole and exemestane) with or without gonadotropin-releasing hormone (GnRH) agonists/antagonists for a minimum of 4 months and be planning to continue on adjuvant endocrine therapy for the duration of the trial without change to therapy, brand or dose. Add-on therapies for breast cancer adjuvant treatment (e.g., cyclin dependent kinase-4 (CDK4) inhibitors) are allowed.
* Participant has a minimum average of 7 moderate to severe hot flashes (HFs) (vasomotor symptoms (VMS)) per day as recorded in the electronic daily diary (data must be available for at least 7 of the last 10 days prior to randomization).
* Has an European Cooperative Oncology Group (ECOG) score 0 or 1.
* Has at least 12-month life expectation.
* Participant is born female.
* Female participant: Is not pregnant and at least 1 of the following conditions apply:

  * Not a woman of childbearing potential (WOCBP)
  * WOCBP who has a negative urine or serum pregnancy test at screening and day 1 and agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final investigational study intervention administration.
* Female participant: Must not be breastfeeding or lactating starting at screening and while the participant is taking investigational study intervention and for 30 days after final investigational study intervention administration.
* Female participant: Must not donate ova starting at first administration of study intervention and while the participant is taking investigational study intervention and for 30 days after final investigational study intervention administration.
* Participant agrees not to participate in another interventional study while participating in the present study until the end of the 1-year extension follow-up period.
* Participant's condition is stable as determined on the basis of medical history and general physical examination (including a bimanual clinical pelvic examination devoid of relevant clinical findings performed at the screening visit), hematology and biochemistry parameters, pulse rate and/or blood pressure and electrocardiogram (ECG) (or showing no clinically relevant deviations obtained within the last 3 months or at screening).
* Participant has no new clinically significant findings on breast examination or from imaging (mammogram or breast ultrasound). Results indicate that the participant is a good candidate for the study. Appropriate documentation includes a written or electronic report. In case of double mastectomy, imaging is not needed.
* Participant has a negative serology panel (including hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody and human immunodeficiency virus (HIV) antibody screens).

Exclusion Criteria:

* Participant has diagnosis of metastatic breast cancer (stage 4).
* Participant has current or history (except complete remission for 5 years or more prior to signing informed consent) of any malignancy except for HR+ breast cancer (stage 0 to 3) or basal cell carcinoma.
* Participant has had surgery or non-surgical (chemotherapy or radiotherapy) treatment for breast cancer within the last 3 months prior to signing informed consent.
* Participant has active liver disease, jaundice, or elevated liver aminotransferases (alanine aminotransferase (ALT) or aspartate aminotransferase (AST)), elevated total bilirubin (TBL) or direct bilirubin (DBL), or elevated alkaline phosphatase (ALP) at screening. A participant with mildly elevated ALT or AST up to \< 2 × upper limit of normal (ULN) can be enrolled if TBL and DBL are normal. Participant with mildly elevated ALP (up to \< 1.5 × ULN) can be enrolled if cholestatic liver disease is excluded and no cause other than fatty liver is diagnosed. Participant with Gilbert's syndrome with elevated TBL may be enrolled as long as DBL, hemoglobin and reticulocytes are normal.
* Participant has creatinine \> 1.5 x ULN; or estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula \< 30 mL/min/1.73 m2 at the screening visit.
* Participant has a history of endometrial hyperplasia or uterine/endometrial cancer.
* Participant has a medical condition or chronic disease (including history of neurological \[including cognitive\], hepatic, renal, cardiovascular, gastrointestinal, pulmonary \[e.g., moderate asthma\], endocrine, or gynecological disease) or malignancy that could confound interpretation of the study outcome.
* Participant uses a prohibited therapy (menopause hormone therapy (MHT), estradiol-containing hormonal contraceptive progestin and progesterone-only medicines, any treatment for VMS \[prescription medications, over-the-counter, or herbal\] or CYP1A2 (cytochrome P450) inhibitors) or is not willing to wash out such drugs; in addition, medications that are contraindicated due to underlying breast cancer diagnosis and the adjuvant endocrine therapy.
* Participant has a known substance abuse or alcohol addiction within 6 months of screening.
* Participant has received any investigational therapy within 90 days or 5 half-lives, whichever is longer, prior to screening.
* Participant has any condition, which makes the participant unsuitable for study participation.
* Participant has a known or suspected hypersensitivity to fezolinetant, the adjuvant endocrine therapy being used, or any components of the formulations used.

Primary outcomes:
measure: Mean change from Baseline to Week 4 in the frequency of moderate to severe VMS
timeFrame: Baseline to Week 4
measure: Mean change from Baseline to Week 12 in the frequency of moderate to severe VMS
timeFrame: Baseline to Week 12
measure: Mean change from Baseline to Week 4 in the severity of moderate to severe VMS
timeFrame: Baseline to Week 4
measure: Mean change from Baseline to Week 12 in the severity of moderate to severe VMS
timeFrame: Baseline to Week 12
Secondary outcomes:
measure: Mean change from Baseline to Week 12 in the MENQOL VMS 1 week recall domain score
timeFrame: Baseline to Week 12
measure: Mean Change from Baseline to Week 12 in the PROMIS SD SF 8b Total (raw) Score
timeFrame: Baseline to Week 12
measure: Mean change from Baseline to Week 24 in the frequency of moderate to severe VMS
timeFrame: Baseline to Week 24
measure: Mean Change from Baseline to Week 24 in the severity of moderate to severe VMS
timeFrame: Baseline to Week 24
measure: Number of participants with Treatment Emergent Adverse Events (TEAEs)
timeFrame: Up to Week 55
measure: Number of participants with Adverse Events of Special Interest (AESIs)
timeFrame: Up to Week 55
measure: Number of participants with laboratory value abnormalities and/or adverse events (AEs)
timeFrame: Up to Week 55
measure: Number of participants with vital sign abnormalities and/or adverse events (AEs)
timeFrame: Up to Week 55
measure: Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)
timeFrame: Up to Week 52
measure: Mean change from Baseline in the frequency of moderate to severe VMS to the average frequency of moderate to severe VMS over Weeks 1 to 3
timeFrame: Baseline and Weeks 1 to 3
measure: Mean Change from Baseline in the frequency of moderate to severe VMS to the average frequency of moderate to severe VMS over Weeks 5 to 11
timeFrame: Baseline and Weeks 5 to 11
measure: Mean change from Baseline in the severity of moderate to severe VMS to the average severity of moderate to severe VMS over weeks 1 to 3
timeFrame: Baseline and Weeks 1 to 3
measure: Mean Change from Baseline in the severity of moderate to severe VMS to the average severity of moderate to severe VMS over weeks 5 to 11
timeFrame: Baseline and Weeks 5 to 11
measure: Percent reduction >/= 50% in the frequency of moderate and severe VMS from baseline
timeFrame: Baseline to Weeks 1, 4, 8 and 12
measure: Percent reduction >/= 75% in the frequency of moderate and severe VMS from baseline
timeFrame: Baseline to Weeks 1, 4, 8 and 12
measure: Percent reduction at 100% in the frequency of moderate and severe VMS from baseline
timeFrame: Baseline to Weeks 1, 4, 8 and 12
measure: Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F) for participants taking tamoxifen
timeFrame: Up to Week 24
measure: Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F) for participants taking aromatase inhibitors
timeFrame: Up to Week 24
measure: PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F) for participants taking tamoxifen
timeFrame: Up to Week 24
measure: PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F) for participants taking aromatase inhibitors
timeFrame: Up to Week 24
measure: PK of Fezolinetant in Plasma: average concentration (Cavg) for participants taking tamoxifen
timeFrame: Up to Week 24
measure: PK of Fezolinetant in Plasma: Cavg for participants taking aromatase inhibitors
timeFrame: Up to Week 24
measure: PK of Fezolinetant in Plasma: trough concentration (Ctrough) for participants taking tamoxifen
timeFrame: Up to Week 24
measure: PK of Fezolinetant in Plasma: Ctrough for participants taking aromatase inhibitors
timeFrame: Up to Week 24
measure: PK of tamoxifen in Plasma: CL/F
timeFrame: Up to Week 24
measure: PK of tamoxifen in Plasma: Vc/F
timeFrame: Up to Week 24
measure: PK of tamoxifen in Plasma: Cavg
timeFrame: Up to Week 24
measure: PK of tamoxifen in Plasma: Ctrough
timeFrame: Up to Week 24
measure: PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: CL/F
timeFrame: Up to Week 24
measure: PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Vc/F
timeFrame: Up to Week 24
measure: PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Cavg
timeFrame: Up to Week 24
measure: PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Ctrough
timeFrame: Up to Week 24
measure: PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: CL/F
timeFrame: Up to Week 24
measure: PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Vc/F
timeFrame: Up to Week 24
measure: PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Cavg
timeFrame: Up to Week 24
measure: PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Ctrough
timeFrame: Up to Week 24
measure: PK of tamoxifen Metabolite endoxifen in Plasma: CL/F
timeFrame: Up to Week 24
measure: PK of tamoxifen Metabolite endoxifen in Plasma: Vc/F
timeFrame: Up to Week 24
measure: PK of tamoxifen Metabolite endoxifen in Plasma: Cavg
timeFrame: Up to Week 24
measure: PK of tamoxifen Metabolite endoxifen in Plasma: Ctrough
timeFrame: Up to Week 24
measure: PK of aromatase inhibitors in Plasma: CL/F
timeFrame: Up to Week 24
measure: PK of aromatase inhibitors in Plasma: Vc/F
timeFrame: Up to Week 24
measure: PK of aromatase inhibitors in Plasma: Cavg
timeFrame: Up to Week 24
measure: PK of aromatase inhibitors in Plasma: Ctrough
timeFrame: Up to Week 24
measure: Mean change from Baseline in the MENQOL Total Score
timeFrame: Baseline to Weeks 4, 8, 12 and 24
measure: Mean change from Baseline in the MENQOL VMS 1-week recall domain score
timeFrame: Baseline to Weeks 4, 8 and 24
measure: Mean change from Baseline in the MENQOL psychosocial 1-week recall domain score
timeFrame: Baseline to Weeks 4, 8, 12 and 24
measure: Mean change from Baseline in the MENQOL physical 1-week recall domain score
timeFrame: Baseline to Weeks 4, 8, 12 and 24
measure: Mean change from Baseline in the MENQOL sexual 1-week recall domain score
timeFrame: Baseline to Weeks 4, 8, 12 and 24
measure: Mean change from Baseline in the PROMIS SD SF 8b Total (raw) Score
timeFrame: Baseline to Weeks 4, 8 and 24
measure: Scores on the Patient Global Impression of Change (PGI-C) VMS
timeFrame: Up to Week 24
measure: Change from Baseline in the Patient Global Impression of Severity (PGI-S) VMS Score
timeFrame: Baseline to Weeks 4, 8, 12 and 24
measure: Scores on the PGI-C sleep disturbance (SD)
timeFrame: Up to Week 24
measure: Change from Baseline in the PGI-S SD Score
timeFrame: Baseline to Weeks 4, 8, 12 and 24
measure: PGI-S SD response
timeFrame: Up to Week 24
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Site CA15002
state: Quebec
city: Quebec City
country: Canada
facility: Site CA15001
state: Quebec
city: Sherbrooke
country: Canada
facility: Site CA15003
state: Quebec
city: Trois-Rivières
country: Canada
facility: Site CA15007
city: Ceske Budejovice
country: Czechia
facility: Site CZ42006
city: Horovice
country: Czechia
facility: Site CZ42003
city: Novy Jicin
country: Czechia
facility: Site CZ42011
city: Olomouc
country: Czechia
facility: Site CZ42001
city: Prague 10
country: Czechia
facility: Site CZ42008
city: Tabor
country: Czechia
facility: Site CZ42004
city: Vodnany
country: Czechia
facility: Site CZ42007
city: Vsetin
country: Czechia
facility: Site CZ42009
city: Aalborg
country: Denmark
facility: Site DK45007
city: Esbjerg
country: Denmark
facility: Site DE45003
city: Naestved
country: Denmark
facility: Site DK45002
city: Sonderborg
country: Denmark
facility: Site DE45008
city: Angers Cedex 9
country: France
facility: Site FR33003
city: Bayonne
country: France
facility: Site FR33001
city: Bordeaux Cedex
country: France
facility: Site FR33005
city: Le Mans
country: France
facility: Site FR33013
city: Lille Cedex
country: France
facility: Site FR33007
city: Lyon Cedex 08
country: France
facility: Site FR33012
city: Montpellier
country: France
facility: Site FR33008
city: Saint Herblain Cedex
country: France
facility: Site FR33002
city: Bottrop
country: Germany
facility: Site DE49001
city: Leipzig
country: Germany
facility: Site DE49009
city: Moenchengladbach
country: Germany
facility: Site DE49007
city: Budapest
country: Hungary
facility: Site HU36008
city: Debrecen
country: Hungary
facility: Site HU36006
city: Eger
country: Hungary
facility: Site HU36001
city: Kecskemet
country: Hungary
facility: Site HU36002
city: Salgotarjan
country: Hungary
facility: Site HU36010
city: Szekesfehervar
country: Hungary
facility: Site HU36003
city: Milano
country: Italy
facility: Site IT39003
city: Reggio Emilia
country: Italy
facility: Site IT39018
city: Terni
country: Italy
facility: Site IT39012
city: Tricase
country: Italy
facility: Site IT39014
city: Breda
country: Netherlands
facility: Site NL31010
city: Dirksland
country: Netherlands
facility: Site NL31006
city: Haarlem
country: Netherlands
facility: Site NL31001
city: Rotterdam
country: Netherlands
facility: Site NL31004
city: Rotterdam
country: Netherlands
facility: Site NL31012
city: Terneuzen
country: Netherlands
facility: Site NL31009
city: Poznan
country: Poland
facility: Site PO48019
state: Skorzewo
city: Bialystok
country: Poland
facility: Site PO48005
city: Bydgoszcz
country: Poland
facility: Site PO48006
city: Katowice
country: Poland
facility: Site PO48004
city: Katowice
country: Poland
facility: Site PO48017
city: Krakow
country: Poland
facility: Site PO48015
city: Lodz
country: Poland
facility: Site PO48007
city: Pila
country: Poland
facility: Site PO48020
city: Poznan
country: Poland
facility: Site PO48002
city: Poznan
country: Poland
facility: Site PO48018
city: Swidnik
country: Poland
facility: Site PO48003
city: Szczecin
country: Poland
facility: Site PO48010
city: Warszawa
country: Poland
facility: Site PO48001
city: Barcelona
country: Spain
facility: Site ES34011
city: Barcelona
country: Spain
facility: Site ES34020
city: Elche
country: Spain
facility: Site ES34010
city: Girona
country: Spain
facility: Site ES34003
city: Granada
country: Spain
facility: Site ES34005
city: Jaen
country: Spain
facility: Site ES34006
city: Leon
country: Spain
facility: Site ES34017
city: Madrid
country: Spain
facility: Site ES34007
city: Madrid
country: Spain
facility: Site ES34022
city: Majadahonda
country: Spain
facility: Site ES34015
city: Murcia
country: Spain
facility: Site ES34002
city: Murcia
country: Spain
facility: Site ES34014
city: Sevilla
country: Spain
facility: Site ES34009
city: Aberdeen
country: United Kingdom
facility: Site GB44018
city: Cambridge
country: United Kingdom
facility: Site GB44016
city: Glasgow
country: United Kingdom
facility: Site GB44006
city: Liverpool
country: United Kingdom
facility: Site GB44002
city: London
country: United Kingdom
facility: Site GB44005
city: Redhill
country: United Kingdom
facility: Site GB44012
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: