A Single-Arm, Open-Label Phase 4 Study of Nirogacestat in Adult Premenopausal Females With Desmoid Tumors/Aggressive Fibromatosis (DT/AF)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 33
- 主要终点
- Ovarian function recovery rate of ovarian toxicity (OT) treatment-emergent adverse events (TEAEs)
研究概览
简要总结
This study is being conducted to study how nirogacestat may affect the ovarian function of adult premenopausal women with progressing desmoid tumors/aggressive fibromatosis.
详细描述
Desmoid tumors, also referred to as aggressive fibromatosis, are rare, locally invasive, slow growing soft tissue tumors. Although considered benign because of their inability to metastasize, desmoid tumors can cause significant morbidity and occasionally mortality in patients.
Nirogacestat is a tumor inhibitor that works by slowing or stopping the growth of tumor cells. Nirogacestat is a tablet taken by mouth and has been approved in the USA for adult patients with progressing desmoid tumors who require systemic treatment.
This is an open-label study to characterize the incidence and ovarian function recovery rates of ovarian toxicity (OT) events and to evaluate the efficacy, safety, and tolerability of nirogacestat in postpubertal and premenopausal females with desmoid tumors (DT).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Participant is female, postpubertal aged ≥18 and ≤40 years of age at the time of signing the informed consent and premenopausal at baseline. Premenopausal is defined as meeting all of the following: Estradiol >30 pg/mL. Follicle-stimulating hormone (FSH) <40 IU/L. Regular menses (e.g., menstrual cycle length of 21 to 35 days) for at least 3 menstrual cycles prior to signing informed consent
- •Participant uses 1 highly effective non-hormonal contraceptive method, has a negative pregnancy test prior to first dose of study treatment), is not breastfeeding, agrees to not harvest or donate eggs for at least 90 days prior to and during the study
- •Participant has histologically confirmed DT/AF with symptomatic or progressive disease requiring systemic treatment
- •Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 at screening
- •Participant has adequate organ and bone marrow function.
排除标准
- •Participant has known malabsorption syndrome or preexisting gastrointestinal conditions that may impair absorption of nirogacestat
- •Participant has experienced any of the following within 6 months of signing informed consent: clinically significant cardiac disease (New York Heart Association Class III or IV), myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, or symptomatic pulmonary embolism.
- •Participant has had lymphoma, leukemia, or any malignancy within the past 5 years at the time of informed consent, except for any locally recurring cancer that has been treated curatively (e.g., resected basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast), with no evidence of metastatic disease for 3 years at the time of informed consent.
- •Participant has known hepatic impairment
- •Participant previously received or is currently receiving gamma secretase inhibitors or anti-Notch antibody therapy
- •Participant is currently using any treatment for DT/AF including tyrosine kinase inhibitors (TKIs) or any investigational treatment 28 days (or 5 half-lives, whichever is longer) prior to the first dose of study treatment
- •Participant is currently using or anticipates using food or drugs that are known strong/moderate cytochrome P450 (CYP) 3A4 inhibitors, or strong CYP3A inducers within 14 days prior to the first dose of study treatment.
- •Participant has a history of polycystic ovary syndrome, hypothalamic amenorrhea, severe endometriosis involving ovaries, family history of primary ovarian insufficiency, any chromosomal abnormality, mutation, gene variant or medical condition associated with early/premature menopause, including a history of OT while on a TKI
- •Participant is currently using or has used hormonal contraception or ovarian suppression within 90 days prior to first dose of study treatment
- •Participant has a history of heavy tobacco smoking (≥20 pack years) or is a current smoker (>1 pack per day)
- •Participant has experienced other severe acute or chronic medical or psychiatric conditions within 1 year of signing informed consent.
- •Participant is unable to comply with study related procedures (including, but not limited to, the completion of a menstrual diary and electronic patient-reported outcomes and ability to return to clinic for hormone level blood draws timed to the menstrual cycle (days 1-5)
研究组 & 干预措施
Nirogacestat
Nirogacestat 150 mg by mouth, twice daily
干预措施: Nirogacestat (Drug)
结局指标
主要结局
Ovarian function recovery rate of ovarian toxicity (OT) treatment-emergent adverse events (TEAEs)
时间窗: Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period
Ovarian function recovery is defined as achieving the resumption of ≥2 consecutive menstrual periods and an FSH level \<30 mIU/mL with concomitant estradiol \<80 pg/mL OR resumption of ≥2 consecutive menstrual periods and AMH level within normal range adjusted for age and pretreatment baseline OR a positive serum β-HCG pregnancy test.
次要结局
- Incidence of OT TEAEs(Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period)
- Time to ovarian function recovery in participants with a TEAE of OT(Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period)
- The incidence of adverse events (AEs) according to toxicities graded by National Cancer Institute (NCI) Common Technology Criteria for Adverse Events (CTCAE) Version 5(Up to 24 cycles (each cycle is 28 days) of treatment and up to 2 years in the Clinical Follow-up Period)