Phase 2 Study of Poly-ICLC in the Treatment of Pediatric Low Grade Gliomas

Poly-ICLC 治疗儿童低级别胶质瘤的 2 期研究

• 批准号: 9125663
• 负责人: DONALD DURDEN
• 金额: $ 40万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-05 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9125663
• 关键词: Phase; Study; Poly; ICLC; Treatment

DESCRIPTION (provided by applicant): Brain tumors are the most common solid tumor diagnosed in childhood and thus account for significant childhood mortality in the United States. Low-grade astrocytomas and gliomas (LGG) are the most common type of brain tumor of childhood (36% of childhood brain tumors). Based on data from the Surveillance, Epidemiology, and End Results (SEER) database published in 2009, it is estimated that the incidence of LGG in the pediatric population is 4,600 cases diagnosed annually in the US. Radiotherapy is avoided or delayed in the treatment of LGG to prevent neurocognitive decline and to prevent transformation to a more malignant grade of tumor (grade III and IV). In this proposal, it is hypothesized that LGG are more likely to respond to poly-ICLC (a TLR3 agonist) and that characterization of signaling pathways for TLR3 in the tumor and stromal compartment will predict response to this therapy. This is an open label, multi-institutional, phase 2 clinical trial of poly-ICLC with dosing of 20 mcg/kg body weight/dose administered intramuscularly (IM) twice weekly to determine the radiographic response rate to poly-ICLC in the treatment of children with recurrent or progressive LGG. Total length of therapy will be two years with each cycle being 28 days in length. The three specific aims are to: 1) determine if poly-ICLC has antitumor activity in the treatment of pediatric recurrent LGG, 2) determine the toxicity of this agent in a LGG cohort and to evaluate a QOL endpoint in patients treated with poly-ICLC, and 3) perform extensive molecular profiling of peripheral blood mononuclear cells (PBMCs), serum and cerebral spinal fluid in patients samples before and after treatment with poly-ICLC in an effort to identify a biomarker signature that will predict responsiveness to this therapy.

描述（由申请人提供）： 脑肿瘤是儿童时期最常见的实体瘤，因此在美国儿童死亡率很高。低度星形细胞瘤和神经胶质瘤 (LGG) 是儿童最常见的脑肿瘤类型（占儿童脑肿瘤的 36%）。根据 2009 年发布的监测、流行病学和最终结果 (SEER) 数据库的数据，估计美国每年诊断出的 LGG 病例为 4,600 例。在治疗 LGG 时避免或延迟放射治疗，以防止神经认知能力下降并防止肿瘤转化为更恶性的级别（III 级和 IV 级）。在该提案中，假设 LGG 更有可能对聚 ICLC（一种 TLR3 激动剂）产生反应，并且肿瘤和基质室中 TLR3 信号通路的表征将预测对此疗法的反应。这是一项聚-ICLC 的开放标签、多机构、2 期临床试验，剂量为 20 mcg/kg 体重/剂量，每周两次肌内注射 (IM)，以确定聚-ICLC 在治疗复发性或进展性 LGG 儿童中的放射学反应率。治疗总长度为两年，每个周期为 28 天。三个具体目标是：1) 确定 Poly-ICLC 在治疗儿科复发性 LGG 中是否具有抗肿瘤活性，2) 确定该药物在 LGG 队列中的毒性，并评估接受 Poly-ICLC 治疗的患者的 QOL 终点，以及 3) 对患者的外周血单核细胞 (PBMC)、血清和脑脊液进行广泛的分子分析 在使用 Poly-ICLC 治疗之前和之后采集样本，以鉴定可预测对该疗法的反应的生物标志物特征。