A Window of Opportunity Trial of Mirdametinib Plus Vorinostat for NF1 Associated, H3K27 Trimethylation Deficient Malignant Peripheral Nerve Sheath Tumor [MPNST]
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Assess the toxicity of the combination of mirdametinib and vorinostat in patients with NF1-associated high grade MPNSTs.
研究概览
简要总结
This is a single center Phase 0 "window of opportunity" trial for the treatment of newly diagnosed, PRC2 deficient, primary malignant peripheral nerve sheath tumors (MPNSTs) with a short course of the combination of mirdametinib and vorinostat prior to the most appropriate standard of care treatment for their specific tumor (typically localized radiation followed by surgical resection). Four to eight patients, 12 years of age or older and meeting the study's biomarker inclusion criteria, would be enrolled onto this trial. After voluntary written consent (assent with parent consent for minors) the patient undergoes MRI and PET imaging of the tumor and a needle biopsy to collect tumor is performed. Patients with histone H3K27 trimethylation deficient MPNST, as confirmed by immunohistochemistry, receive a single 28-day course of mirdametinib and vorinostat at standard oral dosing for each. At day 26, 27, or 28 the patient returns to clinic for a research visit repeating the baseline MRI and PET imaging and the needle biopsy for tumor tissue.
This ends direct study participation. The patient goes on to the most appropriate standard of care treatment for their MPNST. Information about the subsequent standard of care treatment is collected for the purposes of this study.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Known Neurofibromatosis type 1 (NF-1) syndrome based on current diagnostic criteria.
- •Diagnosis of suspected MPNST by PET or MRI imaging
- •Confirmation of histone H3 lysine 27 trimethylation-negative MPSNT by immunohistochemistry
- •Twelve years of age or older
- •Complete blood count (CBC), platelet, liver and kidney function within institutional normal limits performed within 14 days of 1 st dose of study drug.
- •Must be able to swallow capsules.
- •Females of childbearing potential must use highly effective contraception (see inclusion criteria section) from the time of study enrollment through 6 months after the last dose of vorinostat and mirdametinib. Males with partners of childbearing potential must use highly effective contraception from the time of study enrollment through 3 months after the last dose of vorinostat.
- •Provides voluntary written consent prior to any study related activities, with parental/guardian consent and assent for those 12 to 17 years of age at enrollment.
排除标准
- •Pregnant or breastfeeding - females of childbearing potential must have a negative pregnancy test (serum or urine) within 7 days prior to the 1 st dose of the study drugs.
- •Significant cardiac disease
- •Significant eye disease
- •Radiation therapy or chemotherapy in the past year.
研究组 & 干预措施
Experimental group
newly diagnosed, PRC2 deficient, primary malignant peripheral nerve sheath tumors (MPNSTs)
干预措施: mirdametinib and vorinostat (Drug)
结局指标
主要结局
Assess the toxicity of the combination of mirdametinib and vorinostat in patients with NF1-associated high grade MPNSTs.
时间窗: 48 months
As a result of the vaccine, both unique CNS toxicity and edema have been previously observed as soon as 10 days from the initiation of therapy. Neurotoxicity ≤ Grade 3 is an expected risk of this treatment. This will be measured as the number of participants experiencing this adverse event.
Determine the response of therapeutic targets
时间窗: 48 months
measuring phospho-ERK and histone H3K27 acetylation in post-therapy tumor tissue as compared to pre-treatment tumor tissue.
Evaluate the utility of radiographic response to this regimen
时间窗: 48 months
using MRI and PET. Each patient will undergo MRI of the primary lesion and CT/PET scan for staging and assessment of FDG uptake in the tumor at diagnosis and after completing 28 days of therapy with mirdametinib and vorinostat. Each patient will have a diagnostic tumor biopsy performed as a condition of entry into the study and to measure specific molecular tumor markers. A second biopsy will be performed at the completion of protocol therapy to assess tumor response to the therapy and to see if the specific tumor markers have changed as a result of the therapy given.
次要结局
未报告次要终点