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
概览
- 阶段
- 3 期
- 干预措施
- Fezolinetant
- 疾病 / 适应症
- Hot Flashes
- 发起方
- Astellas Pharma Global Development, Inc.
- 入组人数
- 984
- 试验地点
- 227
- 主要终点
- Mean change from Baseline to Week 4 in the frequency of moderate to severe VMS
- 状态
- 进行中（未招募）
- 最后更新
- 26天前
概览
简要总结
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.
研究者
入排标准
入选标准
- •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 (e.g., tamoxifen or aromatase inhibitors, such as anastrozole, letrozole and exemestane) with or without gonadotropin-releasing hormone (GnRH) agonists/antagonists for a minimum of 4 months prior to randomization and be planning to continue on adjuvant endocrine therapy for the duration of the trial without change to therapy, brand or dose. If the participant is taking GnRH agonists/antagonists, therapy must also be stable for a minimum of 4 months prior to randomization. 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
- •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.
排除标准
- •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 (participant can be enrolled if she has undergone a hysterectomy) 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.
研究组 & 干预措施
Fezolinetant
Participants taking tamoxifen or an aromatase inhibitor will receive fezolinetant once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed.
干预措施: Fezolinetant
Fezolinetant
Participants taking tamoxifen or an aromatase inhibitor will receive fezolinetant once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed.
干预措施: Aromatase inhibitor
Placebo
Participants taking tamoxifen or an aromatase inhibitor will receive matching placebo once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed.
干预措施: Placebo
Placebo
Participants taking tamoxifen or an aromatase inhibitor will receive matching placebo once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed.
干预措施: Aromatase inhibitor
Fezolinetant
Participants taking tamoxifen or an aromatase inhibitor will receive fezolinetant once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed.
干预措施: Tamoxifen
Placebo
Participants taking tamoxifen or an aromatase inhibitor will receive matching placebo once daily for 52 weeks. After the end of the 52 week treatment period, participants will continue to participate in the extension follow up until week 104. They will continue to receive the adjuvant endocrine therapy as needed.
干预措施: Tamoxifen
结局指标
主要结局
Mean change from Baseline to Week 4 in the frequency of moderate to severe VMS
时间窗: Baseline to Week 4
Frequency of moderate and severe vasomotor symptoms (VMS) events will be calculated as the sum of moderate and severe VMS events per day.
Mean change from Baseline to Week 12 in the frequency of moderate to severe VMS
时间窗: Baseline to Week 12
Frequency of moderate and severe VMS events will be calculated as the sum of moderate and severe VMS events per day.
Mean change from Baseline to Week 4 in the severity of moderate to severe VMS
时间窗: Baseline to Week 4
The severity of VMS will be calculated using a weighted average of VMS events.
Mean change from Baseline to Week 12 in the severity of moderate to severe VMS
时间窗: Baseline to Week 12
The severity of VMS will be calculated using a weighted average of VMS events.
次要结局
- Mean change from Baseline to Week 12 in the MENQOL VMS 1 week recall domain score(Baseline to Week 12)
- Mean Change from Baseline to Week 12 in the PROMIS SD SF 8b Total (raw) Score(Baseline to Week 12)
- Mean change from Baseline to Week 24 in the frequency of moderate to severe VMS(Baseline to Week 24)
- Mean Change from Baseline to Week 24 in the severity of moderate to severe VMS(Baseline to Week 24)
- Number of participants with Treatment Emergent Adverse Events (TEAEs)(Up to Week 55)
- Number of participants with Adverse Events of Special Interest (AESIs)(Up to Week 55)
- Number of participants with laboratory value abnormalities and/or adverse events (AEs)(Up to Week 55)
- Number of participants with vital sign abnormalities and/or adverse events (AEs)(Up to Week 55)
- Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs)(Up to Week 52)
- 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(Baseline and Weeks 1 to 3)
- 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(Baseline and Weeks 5 to 11)
- 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(Baseline and Weeks 1 to 3)
- 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(Baseline and Weeks 5 to 11)
- Percent reduction >/= 50% in the frequency of moderate and severe VMS from baseline(Baseline to Weeks 1, 4, 8 and 12)
- Percent reduction >/= 75% in the frequency of moderate and severe VMS from baseline(Baseline to Weeks 1, 4, 8 and 12)
- Percent reduction at 100% in the frequency of moderate and severe VMS from baseline(Baseline to Weeks 1, 4, 8 and 12)
- Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F) for participants taking tamoxifen(Up to Week 24)
- Pharmacokinetics (PK) of Fezolinetant in Plasma: Apparent Clearance (CL/F) for participants taking aromatase inhibitors(Up to Week 24)
- PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F) for participants taking tamoxifen(Up to Week 24)
- PK of Fezolinetant in Plasma: apparent volume of distribution (Vc/F) for participants taking aromatase inhibitors(Up to Week 24)
- PK of Fezolinetant in Plasma: average concentration (Cavg) for participants taking tamoxifen(Up to Week 24)
- PK of Fezolinetant in Plasma: Cavg for participants taking aromatase inhibitors(Up to Week 24)
- PK of Fezolinetant in Plasma: trough concentration (Ctrough) for participants taking tamoxifen(Up to Week 24)
- PK of Fezolinetant in Plasma: Ctrough for participants taking aromatase inhibitors(Up to Week 24)
- PK of tamoxifen in Plasma: CL/F(Up to Week 24)
- PK of tamoxifen in Plasma: Vc/F(Up to Week 24)
- PK of tamoxifen in Plasma: Cavg(Up to Week 24)
- PK of tamoxifen in Plasma: Ctrough(Up to Week 24)
- PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: CL/F(Up to Week 24)
- PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Vc/F(Up to Week 24)
- PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Cavg(Up to Week 24)
- PK of tamoxifen Metabolite 4-OH tamoxifen in Plasma: Ctrough(Up to Week 24)
- PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: CL/F(Up to Week 24)
- PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Vc/F(Up to Week 24)
- PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Cavg(Up to Week 24)
- PK of tamoxifen Metabolite N-desmethyltamoxifen in Plasma: Ctrough(Up to Week 24)
- PK of tamoxifen Metabolite endoxifen in Plasma: CL/F(Up to Week 24)
- PK of tamoxifen Metabolite endoxifen in Plasma: Vc/F(Up to Week 24)
- PK of tamoxifen Metabolite endoxifen in Plasma: Cavg(Up to Week 24)
- PK of tamoxifen Metabolite endoxifen in Plasma: Ctrough(Up to Week 24)
- PK of aromatase inhibitors in Plasma: CL/F(Up to Week 24)
- PK of aromatase inhibitors in Plasma: Vc/F(Up to Week 24)
- PK of aromatase inhibitors in Plasma: Cavg(Up to Week 24)
- PK of aromatase inhibitors in Plasma: Ctrough(Up to Week 24)
- Mean change from Baseline in the MENQOL Total Score(Baseline to Weeks 4, 8, 12 and 24)
- Mean change from Baseline in the MENQOL VMS 1-week recall domain score(Baseline to Weeks 4, 8 and 24)
- Mean change from Baseline in the MENQOL psychosocial 1-week recall domain score(Baseline to Weeks 4, 8, 12 and 24)
- Mean change from Baseline in the MENQOL physical 1-week recall domain score(Baseline to Weeks 4, 8, 12 and 24)
- Mean change from Baseline in the MENQOL sexual 1-week recall domain score(Baseline to Weeks 4, 8, 12 and 24)
- Mean change from Baseline in the PROMIS SD SF 8b Total (raw) Score(Baseline to Weeks 4, 8 and 24)
- Scores on the Patient Global Impression of Change (PGI-C) VMS(Up to Week 24)
- Change from Baseline in the Patient Global Impression of Severity (PGI-S) VMS Score(Baseline to Weeks 4, 8, 12 and 24)
- Scores on the PGI-C sleep disturbance (SD)(Up to Week 24)
- Change from Baseline in the PGI-S SD Score(Baseline to Weeks 4, 8, 12 and 24)
- PGI-S SD response(Up to Week 24)