Breast Cancer Early Stage Breast Cancer (Stage 1-3)
Conditions
Keywords
adjuvant endocrine therapy, vasomotor symptoms, tamoxifen, aromatase
Brief summary
This is a phase II, randomized, double-blinded, 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 participants will be randomized in 1:1 fashion to fezolinetant or placebo arm respectively.
Detailed description
This is a phase II, randomized, double-blinded, 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 participants will be randomized in 1:1 fashion to fezolinetant or placebo arm respectively. After the 7-14-day screening period when all the baseline, pre-treatment measures will be collected, we will record daily data on frequency and severity of VMS and calculate weekly averages of both metrics. After the 12 weeks treatment period, formal efficacy analysis will be conducted and the treatment with fezolinetant will be deemed efficacious if the final weekly average of daily frequency of VMS will be significantly reduced compared to the 'week12 - baseline' difference of the placebo arm. Upon conclusion of the formal 12-week treatment assignment, once VMS final assessment has been recorded, we will unblind the study participants to their treatment assignment. Participants will be then allowed to cross over shall they choose to do so. Due to the vast availability of safety and efficacy data in general population, we did not include interim efficacy/futility or safety analysis. Our hypothesis is that neurokinin blockade by fezolinetant will significantly reduce vasomotor symptoms in breast cancer survivors on endocrine therapy (tamoxifen or aromatase-inhibitor) measured by mean change in frequency of moderate to severe VMS based on patient-reported data from baseline to 12-weeks.
Interventions
DRUGFezolinetant
45 mg tablets, administered orally once daily with or without food, to be taken throughout the entire study phase, i.e. 12 weeks
DRUGPlacebo
45 mg tablets, administered orally once daily with or without food, to be taken throughout the entire study phase, i.e. 12 weeks
Sponsors
Yale University
Astellas Pharma US, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Women with diagnosed, histologically confirmed, clinical stage I-III, HR+ invasive breast cancer as defined by ASCO CAP guidelines for whom adjuvant endocrine therapy would be indicated, regardless of HER2 status. Age 18 years and older. Currently on endocrine therapy (tamoxifen or aromatase inhibitors) as part of standard of care treatment for HR+ breast cancer. Endocrine therapy may be administered with or without ovarian suppression and/or CDK4/6 inhibitors as permitted in Section 7.1.1. Participants with HER2-positive disease are eligible and may receive concurrent HER2 monoclonal antibody therapy (e.g., trastuzumab or pertuzumab), but not HER2 antibody-drug conjugates (e.g., ado-trastuzumab emtansine T-DM1, or trastuzumab deruxtecan T-DXd). Willing and able to provide written informed consent/assent for the trial. Postmenopausal as defined by spontaneous amenorrhea for at least 12 consecutive months, spontaneous amenorrhea for at least 6 months with biochemical criteria or menopause (FSH \> 40 IU/L), or bilateral oophorectomy for at least 6 weeks before the screening visit, or if premenopausal chemically suppressed by GnRH agonist therapy with ultrasensitive estradiol level \<10. On endocrine therapy for a minimum of 3 months and has planned duration of 12 weeks left in the treatment regimen. Participants receiving a CDK4/6 inhibitor must have been on treatment for at least 4 weeks prior to enrollment. Experiencing an average of seven or more moderate to severe hot flashes per day over a 7-day period as documented by Symptom Diary during the Screening Period and seeking treatment or relief for VMS. Able to swallow oral formulation of the study agent.
Exclusion criteria
Participants who have a diagnosis of stage IV metastatic disease. Receiving any other cancer treatment other than endocrine therapy. This includes chemotherapy, targeted therapies, and immunotherapy. Receiving cytochrome CYP1A2 inhibitors. Participants who have initiated, discontinued, or had a dose adjustment of treatment for vasomotor symptoms (prescription, over the counter, or herbal) within 28 days prior to screening. Pregnant or lactating patients. Known cirrhosis or active liver disease, jaundice, or elevated liver aminotransferases (ALT or AST) \>2x ULN, or elevated total bilirubin, OR elevated direct bilirubin, or elevated INR, or elevated alkaline phosphatase \>2x ULN. Creatinine \> 1.5 times upper limit of normal; or estimated GFR ≤ 30 mL/min per 1.73 m2 at screening. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of moderate/severe VMS at 12 weeks of treatment with fezolinetant vs. placebo | Baseline to 12 weeks | To evaluate the mean change reduction in frequency of moderate/severe VMS at 12 weeks of treatment with fezolinetant vs. placebo in breast cancer survivors on endocrine therapy (tamoxifen or aromatase inhibitors). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of fezolinetant vs. placebo in reducing the mean daily frequency of moderate/severe VMS | At week 4, after treatment initiation | To evaluate the efficacy of fezolinetant vs. placebo in reducing the mean daily frequency of moderate/severe VMS |
| Regression of mean daily frequency of moderate/severe VMS average | Study duration: weeks 0-12 | To evaluate treatment activity among breast cancer survivors treated with fezolinetant vs placebo over the entire course of the study duration - measure by regression of mean daily frequency of moderate/severe VMS average every week of treatment (weeks 0-12) |
| Change in global quality of life using Functional Assessment of Cancer Therapy - Breast, Endocrine Therapy Symptoms (FACT-B ES) | Baseline to week 12 | To evaluate the difference in global quality of life in breast cancer survivors treated with fezolinetant vs placebo using FACT-B ES. The total score range is 0 to 164, with higher scores indicating better quality of life |
| Differences in sleep quality using PROMIS Sleep Disturbance-Short Form 8b (PROMIS SD SF 8b) | Baseline, week 4 and week 12 | To evaluate the differences in sleep quality in breast cancer survivors' treatment with fezolinetant vs placebo using patient-reported outcomes measurement information System Sleep Disturbance - Short Form 8b (PROMIS SD SF 8b. Total score is calculated by summing the items (range: 8-40), with a higher score meaning more disturbed sleep. |
Countries
United States
Contacts
CONTACTLaura Kane
PRINCIPAL_INVESTIGATORMaryam Lustberg, MD
Yale University
Outcome results
None listed