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A Study of the Drug Selinexor With Radiation Therapy in Patients With Newly-Diagnosed Diffuse Intrinsic Pontine (DIPG) Glioma and High-Grade Glioma (HGG)

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简短的总结

This phase I/II trial tests the safety, side effects, and best dose of selinexor given in combination with standard radiation therapy in treating children and young adults with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG) with a genetic 这种变化被称为H3 K27M突变. 并对selinexor与标准是否结合进行了检测 放射疗法可以使这类患者的肿瘤缩小. 胶质瘤是一种 发生在脑部或脊椎的癌症. 胶质瘤被认为是高风险(或高级别)，当 它正在迅速增长和蔓延. 风险这个词指的是患癌症的几率 治疗后回来. DIPG是HGG的一种亚型，生长在脑桥(脑桥的一部分) brainstem that controls functions like breathing, swallowing, speaking, and eye movements). 这次审判有两个部分. 这两个部分在处理上的唯一区别是 subjects treated in Part 1 may receive a different dose of selinexor than the subjects 第2部分讨论. 在第1部分(也称为剂量发现阶段)，调查人员希望 determine the dose of selinexor that can be given without causing side effects that are too 严重的. 这个剂量被称为最大耐受剂量(MTD)。. 在第2部分(也称为 Efficacy 阶段), investigators want to find out how effective the MTD of selinexor is against HGG或DIPG. Selinexor blocks a protein called CRM1, which may help keep cancer cells from 生长并可能杀死它们. 它是一种被称为选择性的小分子抑制剂 核出口抑制剂. 放射疗法使用高能量杀死肿瘤细胞 缩小肿瘤. selinexor联合放射治疗可能有效 治疗新诊断的DIPG和H3 k27m突变型HGG患者.

主要目的
治疗
研究类型
介入
阶段
阶段I / II

资格

性别
所有
健康的志愿者
No
最低年龄
12个月
最高年龄
21年

入选标准:

  • 步骤0: Patients must be >= 12 months and =< 21 years of age at the time of enrollment on步骤0.
    • 请注意:
      • 这个年龄范围包括对所有HGG患者进行预筛查. 个人 治疗方案可能有不同的年龄标准.
      • 非dipg患者的肿瘤不携带h3k27m突变

        = 18岁将没有资格参加ACNS1821(第一步).

  • 步骤0: Patient is suspected of having localized, newly diagnosed HGG, excluding 转移性疾病，OR患者有DIPG的机构诊断
  • 步骤0:
    • 对于非脑桥肿瘤患者:患者和/或其父母或合法 guardians have signed informed consent for eligibility screening on APEC14B1 Part A.
    • For patients with DIPG: Patient and/or their parents or legal guardians have 已签署的ACNS1821知情同意书.
  • 步骤0:
    • For patients with non-pontine tumors only, the specimens obtained at the time of diagnostic biopsy or surgery must be submitted through APEC14B1 ASAP, preferably 最终手术后5天内
  • 步骤1: Patients must be >= 12 months and =< 21 years of age at the time of enrollment
  • 第一步:患者必须有新诊断的DIPG或HGG(包括DMG).
  • 第一步:地层浸出
    • Patients with newly-diagnosed typical DIPG, defined as tumors with a pontine epicenter and diffuse involvement of at least 2/3 of the pons on at least 1 axial T2加权图像，均符合条件. 不需要组织学证实.
    • Patients with pontine tumors that do not meet radiographic criteria for typical DIPG (e.g.局灶性肿瘤或累及小于2/3脑桥的肿瘤 cross-sectional area with or without extrapontine extension) are 符合条件的 if the 肿瘤活检证实为高级别胶质瘤(如间变性) 星形细胞瘤，胶质母细胞瘤，未另行指定的高级胶质瘤， 和/或H3 k27m突变体)通过机构诊断.
  • 步骤1:地层DMG (H3 K27M突变)
    • Patients must have newly-diagnosed non-pontine H3 K27M-mutant HGG without BRAF V600 or IDH1 mutations as confirmed by Rapid Central Pathology and Molecular 对APEC14B1进行筛选评价
    • 注:患者不需要有可测量或可评估的疾病.e., DMG 患者可以在入组前完全切除肿瘤. 主要的 脊柱肿瘤符合入组条件. 对于罕见的H3 k27m突变HGG 非中线结构(如.g.(大脑半球)，这些病人将会 被视为地层DMG的一部分.
  • 步骤1:地层HGG(无H3 K27M突变)
    • Patients must have newly-diagnosed non-pontine H3 K27M-wild type HGG without BRAF V600 or IDH1 mutations as confirmed by Rapid Central Pathology and Molecular 对APEC14B1进行筛选评价
    • 请注意:
      • Patients who fall in this category and who are >= 18 years of age are not 符合其他标准治疗方案(放疗/替莫唑胺) 这是可行的
      • 患者不需要有可测量或可评估的疾病.e., HGG 患者可以在入组前完全切除肿瘤. 原发性脊柱肿瘤符合入选条件
  • 步骤1: Patients must have a performance status corresponding to Eastern Cooperative ECOG评分为0、1或2分. Use Karnofsky for patients > 16 years of age and Lansky for patients =<16 years of age. 无法行走的病人，因为 of paralysis, but who are up in a wheelchair, will be considered ambulatory for the 评估绩效评分的目的.
  • 步骤1: Peripheral absolute neutrophil count (ANC) >= 1000/uL (within 7 days prior to 1 .报名)
  • 步骤1: Platelet count >= 100,000/uL (transfusion independent) (within 7 days prior to 1 .报名)
  • 步骤1: Hemoglobin >= 8.0 g/dL(可接受红细胞[RBC]输注)(在 第一步登记前7天)
  • 步骤1: Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 毫升/分钟/ 1.73 m^2(在第一步登记前7天内)或 A serum creatinine based on age/gender as follows (within 7 days prior to step 1 注册):
  • 年龄/最大血清肌酐(mg/dL)
    • 1 to < 2 years / male: 0.6; female: 0.6
    • 2 to < 6 years / male: 0.8; female: 0.8
    • 6 to < 10 years / male: 1; female: 1
    • 10 to < 13 years / male: 1.2; female: 1.2
    • 13 to < 16 years / male: 1.5; female: 1.4

    • = 16岁/男:1.7; female: 1.4

      • 步骤1: Total bilirubin =< 1.年龄正常上限(ULN)的5倍
      • 步骤1:血清谷氨酸丙酮酸转氨酶(SGPT)(丙氨酸 aminotransferase [ALT]) =< 135 U/L. 为了本研究的目的，ULN SGPT是45 U/L.
      • 步骤1: Serum amylase =< 1.5 × ULN
      • 步骤1: Serum lipase =< 1.5 × ULN
      • 步骤1: No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination.
      • 步骤1: Patients with seizure disorder may be enrolled if on anticonvulsants 而且控制得很好.
      • 步骤1:患者必须入组，协议治疗必须在不晚的时候开始 影像学诊断后31天(如 仅限未活检的DIPG患者)或最终手术，以两者为准 日后日期(第0天). For patients who have a biopsy followed by resection, the date of resection will be 考虑最终诊断手术的日期. 如果只做活组织检查，那么 活检日期将被认为是最终诊断手术的日期.

排除标准:

  • 步骤1: Patients must not have received any prior therapy for their central nervous 中枢神经系统(CNS)恶性肿瘤，手术和类固醇药物除外.
  • 步骤1: Patients who are currently receiving another investigational drug are not 符合条件的.
  • 步骤1: Patients who are currently receiving other anti-cancer agents are not 符合条件的.
  • 步骤1: Patients >=18 years of age who have H3 K27M-wild type HGG.
  • 1 .感染无法控制的患者.
  • 步骤1:既往接受过实体器官移植的患者.
  • 步骤1: Patients with grade > 1 extrapyramidal movement disorder.
  • 步骤1: Patients with known macular degeneration, uncontrolled glaucoma, or cataracts.
  • 步骤1: Patients with metastatic disease are not 符合条件的; MRI of spine with and without contrast must be performed if metastatic disease is suspected by the treating 医生.
  • 步骤1: Patients with gliomatosis cerebri type 1 or 2 are not 符合条件的, with the H3 k27m突变双丘脑肿瘤除外.
  • 步骤1: Patients who are not able to receive protocol specified radiation therapy.
  • 步骤1:
    • Female patients who are pregnant are in符合条件的 since there is yet no available 关于人类胎儿或致畸毒性的信息.
    • Lactating females are not 符合条件的 unless they have agreed not to breastfeed 她们的婴儿. 目前尚不清楚selinexor是否在人乳中排泄.
    • Female patients of childbearing potential are not 符合条件的 unless a negative 已获得妊娠试验结果.
    • Sexually active patients of reproductive potential are not 符合条件的 unless they have agreed to use two effective methods of birth control (including a medically 公认的屏障避孕法.g.(男用或女用避孕套) duration of their study participation and for 90 days after the last dose of selinexor. 节欲是一种可以接受的节育方法.

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研究统计数据
协议没有.
22-5123
类别
脑癌
首席研究员
Satiro Nakamura De Oliveira
联系
米凯拉·马维斯·亨德森
位置
  • 皇冠hga025大学圣莫尼卡分校
  • 皇冠hga025大学洛杉矶分校韦斯特伍德
为供应商
英国没有.
NCT05099003
有关详细的技术资格，请访问 临床试验.政府.