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

描述(由申请人提供)： 脑瘤是在儿童时期诊断的最常见的实体肿瘤，因此在美国占儿童死亡率的很大一部分。低级别星形细胞瘤和胶质瘤(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，估计美国儿童人群中LGG的发病率为每年4600例确诊病例。在治疗LGG时避免或推迟放射治疗，以防止神经认知能力下降，并防止向更恶性的肿瘤(III和IV级)转化。在这个建议中，假设LGG更有可能对PolyICLC(一种TLR3激动剂)有反应，肿瘤和间质间质中TLR3信号通路的特征将预测对这种治疗的反应。这是一项开放的、多机构的2期临床试验，PolyICLC的剂量为20微克/公斤体重/剂量，每周两次肌肉注射(IM)，以确定PolyICLC在治疗复发或进展性LGG儿童中的放射学响应率。总疗程为两年，每个周期为28天。这三个具体目标是：1)确定PolyICLC在治疗儿童复发性LGG方面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PolyICLC治疗的患者的生活质量终点；以及3)对PolyICLC治疗前后患者样本的外周血单核细胞(PBMC)、血清和脑脊液样本进行广泛的分子图谱分析，以努力确定可预测该疗法疗效的生物标志物特征。

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.