Phase I Trial of Radiation and Lenalidomide in Pediatric Malignant Glioma

放射治疗和来那度胺治疗儿童恶性胶质瘤的 I 期试验

基本信息

批准号：
8938044
负责人：
Katherine e Warren
金额：
$ 5.89万
依托单位：
DIVISION OF BASIC SCIENCES - NCI
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/8938044
关键词：
14 year old 21 year old Accounting Adult Adult Glioma Am 80 Anaplastic astrocytoma Angiogenesis Inhibitors Animal Model Anti-Inflammatory Agents Anti-inflammatory Antineoplastic Agents Biological Markers Blood Brain Neoplasms Brain Stem Glioma Cancer Etiology Cell Death Cells Central Nervous System Neoplasms Cessation of life Characteristics Child Childhood Childhood Central Nervous System Neoplasm Clinical Clinical Trials DNA Repair Diagnosis Diffuse Disease Disease Progression Dose Dose-Limiting Drug Kinetics Dysmyelopoietic Syndromes Eligibility Determination Excision FDA approved Glioblastoma Glioma Laboratories Magnetic Resonance Imaging Maintenance Malignant Childhood Neoplasm Malignant Glioma Malignant Neoplasms Malignant neoplasm of brain Malignant neoplasm of central nervous system Measurable Metabolic Mitotic Monitor Mononuclear Multiple Myeloma Newly Diagnosed Operative Surgical Procedures Oral Outcome Patients Pediatric Brain Tumor Consortium Performance Pharmaceutical Preparations Phase Phase I Clinical Trials Play Pontine structure Prior Chemotherapy Progression-Free Survivals Property Proteins Radiation Radiation Tolerance Radiation therapy Radiation-Sensitizing Agents Recurrence Refractory Resected Role Sample Size Schedule Solid Neoplasm Supratentorial Survival Rate Testing Thalidomide Therapeutic Time Toxic effect Translating Tumor Necrosis Factor-alpha Urine analog base chemotherapeutic agent chemotherapy chromosome 5q loss cytotoxic design human TNF protein improved lenalidomide novel strategies patient population radiation effect response standard care success tumor

项目摘要

This study remains open to accrual. Brain tumors are the most common solid neoplasm in childhood and the second most common group of pediatric cancers. Standard therapeutic options for brain tumors consist of surgical resection, radiation therapy and chemotherapy; yet overall survival rates for malignant brain tumors remain low. Radiation therapy plays a key role in the treatment of diffuse intrinsic pontine gliomas (DIPG) and high-grade gliomas (HGG), and thalidomide has been shown in an animal model to be a radiosensitizer. Lenalidomide, a thalidomide analog with antiangiogenic, cytotoxic and immunomodulatory effects, is being evaluated for the treatment of CNS tumors, and has shown tolerability and activity in pediatric studies. Objectives: To determine the tolerability and toxicity profile of oral lenalidomide when administered to children with newly diagnosed HGG and DIPG with concurrent radiation at doses up to 116 mg/m2/day. To evaluate long-term tolerability of lenalidomide in children with newly-diagnosed HGG and DIPG To evaluate magnetic resonance imaging (MRI) sequences for noninvasive monitoring of metabolic and biologic changes in malignant brain tumors with therapy. To estimate 6 month and 12 month progression free survival (PFS) and overall survival (OS) in this patient population. To determine if angiogenic and/or immunomodulatory biomarkers in the blood and urine correlate with toxicity and disease response. To determine the rate of CNS metastatic disease in patients treated with antiangiogenic chemotherapy. To determine any correlation of steady state pharmacokinetics of lenalidomide with time to progression, number and type of toxicities, and dose limiting toxicities. Eligibility: Children with newly diagnosed HGG or DIPG,less than 21 years of age, no prior chemotherapy or radiation therapy, and performance score greater than or equal to 60%. Children with HGG must have an inoperable or incompletely resected tumor. Clinical laboratory tests must be within stated limits. Design: There will be two phases to therapy on this study, the Radiation Phase and the Maintenance Phase. The MTD will be determined by tolerability during the Radiation Phase. Eligible patients will receive radiation therapy five days per week to a prescription dose of 54-55.8 Gy, with concurrent administration of lenalidomide daily in a standard Phase I dose escalation design. At the conclusion of radiation therapy, there will be a two week break followed by maintenance dosing of lenalidomide for 21 days of a 28 day course, until unacceptable toxicity, disease progression or completion of 24 courses of lenalidomide beyond radiotherapy. Using a standard phase I dose escalation design, the total sample size and the study duration are expected to be 18 30 patients and 5-6 years, respectively.

这项研究仍然对应计开放。脑肿瘤是儿童期最常见的实体肿瘤，也是第二大常见的儿科癌症。脑肿瘤的标准治疗选择包括手术切除、放射治疗和化疗；然而，恶性脑肿瘤的总体生存率仍然很低。放射治疗在弥漫性脑桥胶质瘤 (DIPG) 和高级别胶质瘤 (HGG) 的治疗中发挥着关键作用，沙利度胺已在动物模型中被证明是一种放射增敏剂。来那度胺是一种沙利度胺类似物，具有抗血管生成、细胞毒性和免疫调节作用，目前正在评估其治疗中枢神经系统肿瘤的效果，并在儿科研究中显示出耐受性和活性。目的：确定新诊断的 HGG 和 DIPG 儿童接受最高 116 mg/m2/天剂量的口服来那度胺的耐受性和毒性特征。评估新诊断 HGG 和 DIPG 儿童对来那度胺的长期耐受性评估磁共振成像 (MRI) 序列，用于无创监测恶性脑肿瘤治疗后的代谢和生物学变化。估计该患者群体的 6 个月和 12 个月无进展生存期 (PFS) 和总生存期 (OS)。确定血液和尿液中的血管生成和/或免疫调节生物标志物是否与毒性和疾病反应相关。确定接受抗血管生成化疗的患者中枢神经系统转移性疾病的发生率。确定来那度胺的稳态药代动力学与进展时间、毒性数量和类型以及剂量限制性毒性的相关性。资格：新诊断HGG或DIPG的儿童，年龄小于21岁，既往未接受化疗或放疗，体能评分大于或等于60%。患有 HGG 的儿童必须患有无法手术或未完全切除的肿瘤。临床实验室测试必须在规定的限度内。设计：本研究的治疗将分为两个阶段：放射阶段和维持阶段。 MTD 将由辐射阶段的耐受性决定。符合条件的患者将每周接受五天放射治疗，处方剂量为 54-55.8 Gy，同时按照标准 I 期剂量递增设计每天给予来那度胺。放射治疗结束时，将有两周的休息时间，然后在 28 天疗程中维持 21 天来那度胺剂量，直到出现不可接受的毒性、疾病进展或完成放疗后的 24 个来那度胺疗程。采用标准的 I 期剂量递增设计，预计总样本量和研究持续时间分别为 18-30 名患者和 5-6 年。