Fezolinetant for the Improvement of Vasomotor Symptoms in Breast Cancer Patients Taking Endocrine Therapy, VENT Trial

NCT06617455 | Terminated Phase 2 DMC FDA Drug

• 3 other identifiers: UMCC 2024.059NCI-2024-06543HUM00256706
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well fezolinetant works in improving vasomotor symptoms (VMS) in breast cancer patients taking endocrine therapy (ET). Anti-hormone treatments are effective for lowering the risk of breast cancer but can cause bothersome VMS, such as hot flashes and night sweats. Fezolinetant inhibits the activity of the neurokinin type 3 receptor and has shown activity against VMS in postmenopausal women. Taking fezolinetant may work well at improving VMS in breast cancer patients taking ET.

Conditions

Anatomic Stage I Breast Cancer AJCC v8; Anatomic Stage II Breast Cancer AJCC v8; Anatomic Stage III Breast Cancer AJCC v8; Breast Ductal Carcinoma In Situ; Localized Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Change in frequency of vasomotor symptoms (VMS)

  Will perform an intent-to-treat analysis. The mean change in frequency of VMS with 4 weeks of fezolinetant versus placebo will be reported with the corresponding 95% confidence interval. Initial analysis will use a paired t-test of the mean change in frequency of VMS with 4 weeks of treatment with drug and placebo.

  Baseline to day 71

Secondary Outcomes (6)

• Change of the severity of VMS

  Baseline to day 71

• Change of the hot flash score

  Baseline to day 71

• Change of the Menopause-Specific Quality of Life (MENQOL) hot flash subscore

  Baseline to day 71

• Patient Global Impression of Change (PGIC) for hot flashes and night sweats

  Baseline to day 71

• Change of the Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance

  Baseline to day 71

Study Arms (2)

Arm I (fezolinetant, placebo)

EXPERIMENTAL

Patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.

Procedure: Biospecimen Collection; Drug: Fezolinetant; Drug: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Arm II (placebo, fezolinetant)

EXPERIMENTAL

Patients receive placebo PO QD for 28 days in the absence of unacceptable toxicity. Patients then go through a washout period and take no study medication for the next 14 days. Following the washout, patients receive fezolinetant PO QD for 28 days in the absence of unacceptable toxicity. Patients undergo collection of blood samples throughout the study.

Procedure: Biospecimen Collection; Drug: Fezolinetant; Drug: Placebo Administration; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Arm I (fezolinetant, placebo); Arm II (placebo, fezolinetant)

Fezolinetant DRUG

Given PO

Arm I (fezolinetant, placebo); Arm II (placebo, fezolinetant)

Placebo Administration DRUG

Given PO

Arm I (fezolinetant, placebo); Arm II (placebo, fezolinetant)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Arm I (fezolinetant, placebo); Arm II (placebo, fezolinetant)

Questionnaire Administration OTHER

Ancillary studies

Arm I (fezolinetant, placebo); Arm II (placebo, fezolinetant)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female subject aged ≥ 18 years
• Taking endocrine therapy (tamoxifen, anastrozole, exemestane, or letrozole) for adjuvant treatment of stage 1-3 breast cancer or for chemoprevention (breast ductal carcinoma in situ \[DCIS\] or high risk)
• Planning to take the same endocrine therapy for at least 10 weeks after study drug initiation
• Report 28 or more VMS episodes, at least some of which are severe or bothersome, during the 7-day screening period
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 2 x upper limit of normal (ULN) within 28 days prior to randomization
• Total bilirubin \< 2 x ULN within 28 days prior to randomization
• Completion of chemotherapy, if given. Concurrent use of gonadotropin releasing hormone agonist (GnRHa) therapy, anti-HER2 therapy, bisphosphonate therapy, poly adenosine diphosphate-ribose polymerase (PARP) inhibitor therapy, and abemaciclib therapy is permitted
• Patients receiving treatment with selective serotonin reuptake inhibitor (SSRIs), serotonin and norepinephrine reuptake inhibitor (SNRIs), gabapentinoids, clonidine, or oxybutynin must have been taking a stable dose for at least 30 days prior to enrollment if they plan to continue the drug during study participation, and willing to remain on the treatment for the duration of study participation. If they do not plan to take the medication during study participation, they should stop the medication at least 7 days before the start of the VMS screening period
• Patients taking over-the-counter supplements or herbal medications for treatment of VMS must stop the medication at least 7 days before the start of the VMS screening period
• Able to self-complete questionnaires in English
• Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
• For women of childbearing potential, participants must agree to use an effective contraceptive method during protocol therapy and for 3 months following completion of protocol therapy with details provided as a part of the consent process and must have a negative pregnancy test at screening. In addition to routine contraceptive methods, "effective contraception" also includes refraining from sexual activity that might result in pregnancy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) including hysterectomy, bilateral oophorectomy, and bilateral tubal ligation/occlusion

You may not qualify if:

• Metastatic breast cancer
• Prior treatment with fezolinetant
• Known severe renal disease (estimated glomerular filtration rate \[eGFR\] less than 30 mL/min/1.73 m\^2)
• Known cirrhosis
• Pregnant or breast feeding, or plan to become pregnant during the study period or within 3 months of completing study medication
• Concomitant use of CYP1A2 inhibitors, including but not limited to fluvoxamine, ciprofloxacin, cimetidine, citalopram, and ribociclib
• Concomitant use of systemic or transdermal estrogen products
• Known allergy or hypersensitivity to fezolinetant or any of the excipients in the medication
• Unable to take oral medications
• Any medical condition that would interfere with the absorption of study medication. Prior gastric bypass is permitted
• Concurrent medical disease that could confound or interfere with evaluation of VMS
• Patients with a prior or concurrent malignancy whose natural history or treatment, in the opinion of the treating investigator, has the potential to interfere with the safety or efficacy assessment of the investigational regimen
• Patients who are participating concurrently in another interventional study (actually receiving a study medication) or participated in an interventional study within 30 days prior to screening or received any investigational drug within 30 days or within 5 half-lives prior to screening, whichever is longer

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Breast Cancer Research Foundation: collaborator

Study Sites (1)

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Carcinoma, Intraductal, Noninfiltrating

Interventions

Specimen Handling; fezolinetant

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Breast Carcinoma In Situ; Carcinoma in Situ; Neoplasms, Ductal, Lobular, and Medullary

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Norah L Henry

  University of Michigan Rogel Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All study drug will be blinded to the patients, the study investigators, and the study coordinators to ensure masking of the treatments. The statistician and the study investigators will remain blinded until the study database is locked. The only study personnel that will not be blinded are the research pharmacy staff in order to facilitate randomization codes and treatment delivery, and in case emergency unblinding is required.
• Purpose: SUPPORTIVE CARE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2024
• First Posted: September 27, 2024
• Study Start: October 31, 2024
• Primary Completion: October 22, 2025
• Study Completion: November 21, 2025
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: researchers can request data once the primary analysis has been published
• Access Criteria: deidentified data will be available to researchers upon reasonable request

Locations

US (1)