Fezolinetant for Hot Flashes in Breast Cancer

Recruiting at 65 trial locations

Overseen By Astellas Pharma Global Development, Inc.

Age: 18+

Sex: Female

Trial Phase: Phase 3

Sponsor: Astellas Pharma Global Development, Inc.

Must be taking: Endocrine therapy

Must not be taking: Hormone therapy, CYP1A2 inhibitors

Disqualifiers: Metastatic cancer, Active liver disease, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 52 weeks

540 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires participants to continue their current hormone therapy for breast cancer without changes. However, you must stop any menopause hormone therapy, certain hormonal contraceptives, and treatments for hot flashes before joining the study.

What data supports the effectiveness of the drug fezolinetant for hot flashes in breast cancer patients?

Fezolinetant is effective in reducing hot flashes in menopausal women by blocking a specific receptor in the brain, and it has been approved for this use in the USA. While this approval is for menopausal hot flashes, it suggests potential for similar effectiveness in breast cancer patients experiencing hot flashes. ^{1 2 3 4 5}

Is fezolinetant safe for humans?

Fezolinetant has been studied for treating hot flashes due to menopause, and common side effects include headaches and stomach issues. Some people also experienced increased liver enzyme levels, which can indicate liver stress. ^{1 2 3 6 7}

How is the drug fezolinetant different from other treatments for hot flashes in breast cancer?

Fezolinetant is unique because it is a non-hormonal drug that works by blocking the neurokinin 3 receptor, which helps regulate body temperature, making it different from traditional hormone therapies that have more side effects. ^{1 2 3 4 6}

Research Team

Medical Director

Principal Investigator

Astellas Pharma Global Development, Inc.

Eligibility Criteria

This trial is for women over 18 with breast cancer stages 0-3+, undergoing hormone therapy and experiencing at least 7 moderate to severe hot flashes daily. They must not be breastfeeding, expect to live at least another year, and agree to use contraception. Women cannot join if they are of childbearing potential or plan changes in their cancer treatment.

Inclusion Criteria

I had breast cancer stages 0-3 that was hormone receptor positive.

I have been on a stable breast cancer hormone treatment for at least 4 months and plan to continue.

I am fully active or restricted in physically strenuous activity but can do light work.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive fezolinetant or placebo once daily for 52 weeks to treat hot flashes

52 weeks

Visits every 4 weeks (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 weeks

1 visit (in-person), 2 follow-up calls

Extension Follow-up

Participants continue to be monitored for long-term effects and safety until week 104

49 weeks

Treatment Details

Interventions

• Fezolinetant

Trial Overview The study tests Fezolinetant's effectiveness against hot flashes compared to a placebo in women receiving hormone therapy for breast cancer. Participants will randomly receive either Fezolinetant or a placebo, without knowing which one, and take it daily for a year while tracking their symptoms.

Participant Groups

Group I: Fezolinetant Experimental Treatment 3 Interventions

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.

Group II: Placebo Placebo Group 3 Interventions

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.

Fezolinetant is already approved in United States, European Union for the following indications:

Approved in United States as Veozah for:

• Moderate to severe vasomotor symptoms due to menopause

Approved in European Union as Veoza for:

• Hot flushes (vasomotor symptoms) associated with menopause

Who Is Running the Clinical Trial?

Astellas Pharma Global Development, Inc.

Lead Sponsor

Trials

204

Recruited

123,000+

Tadaaki Taniguchi

Astellas Pharma Global Development, Inc.

Chief Medical Officer

M.D., Ph.D.

Naoki Okamura

Astellas Pharma Global Development, Inc.

Chief Executive Officer

Not available

Findings from Research

Fezolinetant is a new oral medication that acts as a neurokinin 3 receptor (NK3R) antagonist, providing a non-hormonal approach to treat moderate to severe hot flashes associated with menopause.

It received its first approval in the USA in May 2023, marking a significant milestone in its development for managing vasomotor symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fezolinetant: First Approval. Lee, A.[2023]

Fezolinetant, a neurokinin 3 receptor antagonist, is being studied for its potential to treat moderate-to-severe menopausal symptoms, particularly vasomotor symptoms like hot flashes.

Recent research indicates that fezolinetant has shown promising safety and efficacy in alleviating these menopausal symptoms, suggesting it could be a valuable treatment option for women experiencing menopause.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurokinin 3 receptor antagonists for menopausal vasomotor symptoms, an appraisal. Gompel, A., Stuenkel, CA.[2023]

Menopausal hot flashes are common and can be very uncomfortable, but Menopausal Hormone Therapy (MHT) is effective in treating them, although it comes with risks that can limit its use.

Fezolinetant, a new nonhormonal treatment that works by blocking NK3 receptors, has recently been approved by the FDA as a promising alternative for managing menopausal hot flashes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurokinin 3 receptor antagonism for menopausal hot flashes. Comninos, AN., Dhillo, WS.[2023]

Aromatase inhibitors, a newer class of drugs for breast cancer treatment, offer a more selective option compared to traditional antiestrogens like tamoxifen, especially for menopausal women.

These inhibitors are effective in patients with tamoxifen-resistant metastatic cancer and are being explored as alternatives in first-line therapy and neoadjuvant settings, although further research is needed to address remaining questions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Aromatase inhibitors: therapeutic outlook]. Namer, M.[2009]

Letrozole, a third-generation aromatase inhibitor, has been shown to be more effective than tamoxifen and other treatments like megestrol acetate for advanced breast cancer in postmenopausal women, improving disease-free survival rates significantly.

In recent trials, letrozole demonstrated superior outcomes in both first-line and adjuvant settings, suggesting it may be a preferred option for treating hormone receptor-positive breast cancer, especially after initial tamoxifen therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Letrozole in the treatment of breast cancer. Mouridsen, HT., Bhatnagar, AS.[2019]

Fezolinetant effectively reduces the frequency and severity of vasomotor symptoms associated with menopause by inhibiting neurokinin B from binding to its receptor in the hypothalamus, as shown in clinical trials.

While fezolinetant is superior to placebo, common side effects include headaches, gastrointestinal issues, and elevated liver enzymes, providing a nonhormonal alternative for patients who may not tolerate hormone therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fezolinetant: A New Nonhormonal Treatment for Vasomotor Symptoms. Onge, ES., Phillips, B., Miller, L.[2023]

In a phase 2b study involving 352 menopausal women, fezolinetant, a selective neurokinin 3 receptor antagonist, significantly reduced the frequency and severity of moderate to severe vasomotor symptoms (VMS) compared to placebo, with reductions of up to 3.5 episodes per day at week 4.

Fezolinetant was well-tolerated, with mostly mild to moderate side effects and no serious treatment-related adverse events, making it a promising non-hormonal option for managing menopausal VMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. Fraser, GL., Lederman, S., Waldbaum, A., et al.[2022]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Fezolinetant: First Approval. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Neurokinin 3 receptor antagonists for menopausal vasomotor symptoms, an appraisal. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Neurokinin 3 receptor antagonism for menopausal hot flashes. [2023]

4. France pubmed.ncbi.nlm.nih.gov

[Aromatase inhibitors: therapeutic outlook]. [2009]

5. England pubmed.ncbi.nlm.nih.gov

Letrozole in the treatment of breast cancer. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Fezolinetant: A New Nonhormonal Treatment for Vasomotor Symptoms. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

A phase 2b, randomized, placebo-controlled, double-blind, dose-ranging study of the neurokinin 3 receptor antagonist fezolinetant for vasomotor symptoms associated with menopause. [2022]