Overview
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.
Description
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. After the 7-14-day screening period when all the baseline, pre-treatment measures will be collected, investigators 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, investigators 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, investigators did not include interim efficacy/futility or safety analysis.
Investigators 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.
Eligibility
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.
BMI of 18-38 kg/m2
Age 40-65
Currently on endocrine therapy (tamoxifen or aromatase inhibitors)
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.
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 received any treatment for vasomotor symptoms (prescription, over the counter, or herbal) for the last 28 days.
Pregnant or lactating patients
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.