Fezolinetant for Breast Cancer

Overseen By Stephanie Ladd

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Yale University

Must be taking: Endocrine therapy

Must not be taking: CYP1A2 inhibitors

Disqualifiers: Stage IV cancer, Liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

92 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial does not specify that you need to stop taking your current medications, but you must be on endocrine therapy (like tamoxifen or aromatase inhibitors) and not be receiving other cancer treatments or certain medications for hot flashes. It's best to discuss your specific medications with the trial team.

Is fezolinetant safe for humans?

Fezolinetant has been studied for treating menopause symptoms, and common side effects include headaches and stomach issues, with some reports of increased liver enzyme levels. It has been approved in the USA for menopause-related symptoms, indicating it is generally considered safe for this use. ^{1 2 3 4 5}

What is the purpose of this trial?

This is a phase II, randomized, placebo-controlled trial designed to evaluate the efficacy of fezolinetant (45 mg a day) vs. placebo in reducing moderate to severe vasomotor symptoms (VMS) in breast cancer survivors on endocrine therapy (tamoxifen, aromatase inhibitors). The trial will proceed in a single stage and the total of 92 patients will be randomized in 1:1 fashion to fezolinetant or placebo arm respectively.

Research Team

Maryam Lustberg, MD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for women who have survived breast cancer and are currently on endocrine therapy (like tamoxifen or aromatase inhibitors). They should be experiencing moderate to severe hot flashes, also known as vasomotor symptoms.

Inclusion Criteria

I am a woman with early to mid-stage hormone-positive breast cancer.

Willing and able to provide written informed consent/assent for the trial

I am currently taking hormone therapy for cancer.

Exclusion Criteria

Judgement by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements

Pregnant or lactating patients

My cancer has spread to other parts of my body.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive fezolinetant or placebo for 12 weeks to evaluate the reduction in vasomotor symptoms

12 weeks

Weekly data collection (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Crossover

Participants may choose to cross over to the other treatment arm after unblinding

Treatment Details

Interventions

• Fezolinetant

Trial Overview The study is testing Fezolinetant, a new treatment given at 45 mg daily, against a placebo. It's designed to see if it helps reduce hot flashes in breast cancer survivors on hormone treatments. Participants will be randomly assigned to either the Fezolinetant group or the placebo group.

Participant Groups

Group I: Fezolinetant Active Control 1 Intervention

Fezolinetant is an oral medication, and the first neurokinin 3 (NK3) receptor antagonist approved by the FDA in May 2023 for treatment of moderate to severe hot flashes due to menopause. It blocks the activities of the NK3 receptor which is involved in the brain's regulation of body temperature.

Group II: Placebo Placebo Group 1 Intervention

Patients will be given placebo tablets to compare to active comparator.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Astellas Pharma US, Inc.

Industry Sponsor

Trials

90

Recruited

12,900+

Naoki Okamura

Astellas Pharma US, Inc.

Chief Executive Officer since 2023

Not available

Tadaaki Taniguchi

Astellas Pharma US, Inc.

Chief Medical Officer since 2023

MD, PhD

Findings from Research

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]

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]

In a study of 3,046 postmenopausal women with ductal carcinoma in situ, 28.5% discontinued treatment with anastrozole or tamoxifen, with specific adverse events like thrombosis and arthralgia linked to discontinuation of both drugs.

Patient-reported outcomes (PROs) such as pain interference and hot flashes were significant factors in discontinuing tamoxifen, while only hot flashes were associated with discontinuation of anastrozole, highlighting the importance of both adverse events and patient experiences in treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity Index, Patient-Reported Outcomes, and Early Discontinuation of Endocrine Therapy for Breast Cancer Risk Reduction in NRG Oncology/NSABP B-35. Henry, NL., Kim, S., Hays, RD., et al.[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]

References

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

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

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

Fezolinetant: First Approval. [2023]

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

Toxicity Index, Patient-Reported Outcomes, and Early Discontinuation of Endocrine Therapy for Breast Cancer Risk Reduction in NRG Oncology/NSABP B-35. [2023]

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

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

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

Effect of the neurokinin 3 receptor antagonist fezolinetant on patient-reported outcomes in postmenopausal women with vasomotor symptoms: results of a randomized, placebo-controlled, double-blind, dose-ranging study (VESTA). [2022]