Evaluation of the Response and Non-response of Nirogacestat in Desmoid Tumors- Clinical Study
概览
- 阶段
- 2 期
- 干预措施
- Nirogacestat
- 疾病 / 适应症
- Tumor
- 发起方
- M.D. Anderson Cancer Center
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
- 状态
- 招募中
- 最后更新
- 19天前
概览
简要总结
To learn about the safety and effects of an investigational drug called nirogacestat when given to participants with a desmoid tumor/aggressive fibromatosis
详细描述
Primary Objectives: • To identify biomarkers associated with response and non-response to nirogacestat in participants with desmoid tumors (DT). Secondary Objectives: * To assess the 12-month progression-free survival (PFS of participants with DT who receive nirogacestat at 150 mg or 100 mg BID. * To assess MRI volumetric and functional parameters associated with response and non-response to nirogacestat in participants with DT. * To evaluate the histopathological changes in DT biopsy specimens. * To evaluate the safety and tolerability of nirogacestat in participants with DT. Exploratory Objectives: * To assess clinical benefit and tumor response by additional MRI-based measurements including MRI-modified Choi criteria and WHO. * To evaluate MRI parameters such as intensity histogram analysis from T2-weighted image (T2-WI), short inversion time inversion-recovery (T2-STIR), diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping, post-contrast Water Dixon, perfusion-weighted imaging, and susceptibility-weighted imaging (SWI) with contrast and correlate with therapeutic response and clinical outcome. * To assess the dynamics and concordance of circulating tumor cells (CTCs) in the blood compartment and tumor burden during nirogacestat treatment. * To identify cell-free DNA (cfDNA) biomarkers associated with response and non-response to nirogacestat in patients with DT. * To understand the impact of dose on the incidence of ovarian dysfunction in women of childbearing potential (WOCBP).
研究者
入排标准
入选标准
- •This study will enroll approximately 40 participants diagnosed with DT. Participants must meet the following eligibility criteria to be enrolled:
- •Age ≥ 18 years. Individuals younger than 18 years old are excluded. More than 99% of the population evaluated at MDACC with a diagnosis of DT is older than
- •Sixty-three percent of the population with a diagnosis of DT evaluated at MDACC are 10 - 54 years old. The remaining 37 percent are older than 54 years old. Additionally, most of the robust data related to dosing or adverse event data currently available on the use of nirogacestat is in adults
- •Histologically documented DT with evidence of radiographic tumor progression (≥ 10% or absolute increase in dimensions of ≥ 10 mm in maximal diameter) in unidimensional measurement within the previous 18 months. Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam
- •Recurrent or primary disease
- •Symptomatic disease or impending morbidity (as defined by physician) and patient and physician agree treatment would be of benefit
- •Treatment naïve or progression on or after any prior therapy for DT. Participant must have discontinued prior therapy for at least 28 days or 5 half-lives of the drug, whichever is greater. All toxicities from prior therapy must be resolved to Grade ≤ 1 or clinical baseline. There is no limit on the number of previous systemic treatments received
- •Able to tolerate radiographic progression (up to 20% increase in tumor longest diameter) as determined by treating oncologist based on morbidity and tumor growth is not threatening vital structures
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Are appropriate for systemic therapy
排除标准
- •Participants are excluded from this study if any of the following criteria apply:
- •Unable to undergo serial biopsies
- •Participants with familial adenomatous polyposis
- •Unable to tolerate MRI or for whom MRI is contraindicated
- •Pregnant or breastfeeding women are excluded from this study. Based on findings in animal studies, oral administration of nirogacestat to pregnant rats during the period of organogenesis resulted in embryo-fetal toxicities at maternal exposures that were significantly lower than adult human exposures at the recommended dose of 150 mg twice daily. Nirogacestat should be avoided during pregnancy
- •There is no data regarding the presence of nirogacestat or its metabolites in either human or animal milk or its effects on a breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child from nirogacestat, advise women not to breastfeed during treatment with nirogacestat.
- •Known hypersensitivity to nirogacestat or any of its excipients
- •Participants requiring the use of any excluded concomitant medications listed in Table 2 during the course of the study
- •Unable to comply with study-related procedures in the opinion of the investigator
- •Patients with cognitive impairment requiring a legally authorized representative for consent
研究组 & 干预措施
nirogacestat
Participants will take nirogacestat by mouth every day of each 28-day study cycle. Based on when you enroll in this study, you will take nirogacestat either 1 time a day at about the same time each day OR 2 times a day, about 12 hours apart.
干预措施: Nirogacestat
结局指标
主要结局
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
时间窗: through study completion; an average of 1 year.