Phase II Study of 44Gy from 131I-81C6 for CNS Tumors

131I-81C6 44Gy 治疗中枢神经系统肿瘤的 II 期研究

• 批准号: 6740022
• 负责人: DAVID A REARDON
• 金额: $ 31.86万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-29 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6740022
• 关键词: adult human (21+); clinical research; clinical trial phase II; glioblastoma multiforme; human subject; human therapy evaluation; iodine; monoclonal antibody; neoplasm /cancer radioimmunotherapy; patient oriented research; quality of life; radiation therapy dosage; radionuclides; tenascin; toxicant interaction

DESCRIPTION (provided by applicant): The outcome for patients with glioblastoma multiforme, the most common primary malignant brain tumor, remains dismal. Median survival with current therapy including surgery, radiotherapy and chemotherapy remains 40-50 weeks from diagnosis while available salvage therapies are ineffective following recurrence. Most cases progress at the primary site indicating that local control is the critical first step to improve outcome. In response to the dire need for effective, innovative therapies for patients with malignant brain tumors, our center has developed radiolabeled monoclonal antibodies (mAB) that specifically target tumor antigens. 81C6, a murine IgG2b mAB reacts with an isoform of the extracellular matrix protein tenascin which is highly upregulated and expressed by malignant glioma. Previously completed phase I and II studies in which a fixed dose of 131I-labeled 81C6 was administered directly into the surgical created resection cavity (SCRC), confirmed that this approach improves survival for patients with malignant glioma with acceptable toxicity. A key observation from dosimetry studies accompanying these trials is the demonstration that outcome correlated most closely with delivered dose to the SCRC perimeter. Specifically, patients who received less than 44 Gy to the SCRC perimeter had minimal toxicity from radionecrosis but had a higher rate of tumor recurrence. Conversely those patients who received more than 44 Gy had a lower rate of tumor recurrence but a higher rate of symptomatic radionecrosis. Our HYPOTHESIS is that our phase II study with 131I -81C6 administered to deliver 44 Gy to the 2 cm SCRC perimeter will improve survival of patients with newly diagnosed malignant glioma while minimizing radiation injury to normal CNS tissue. The SPECIFIC AIMS of this proposal are: Specific Aim 1. To define the efficacy of 131I -labeled anti-tenascin monoclonal antibody 81C6 administered at a dose to deliver 44 Gy to the 2 cm perimeter of resection cavity of patients with newly diagnosed malignant glioma; Specific Aim 2. To further define the toxicity of this approach and Specific Aim 3.To determine the impact of this therapy on quality of life.

描述（由申请人提供）：最常见的原发性恶性脑肿瘤的胶质母细胞瘤患者的结果仍然令人沮丧。当前疗法（包括手术，放疗和化学疗法）的中位生存期在诊断后仍为40-50周，而可用的救助疗法在复发后无效。大多数情况在主要地点进行，表明局部控制是改善预后的关键第一步。为了应对恶性脑肿瘤患者的有效，创新的疗法的恐惧需求，我们的中心已经开发了放射标记的单克隆抗体（MAB），这些抗体（MAB）专门针对肿瘤抗原。 81C6，鼠IgG2b mAb与细胞外基质蛋白替氏蛋白的同工型反应，该基质蛋白替氏蛋白被恶性神经胶质瘤高度上调和表达。先前完成的I期和II期研究，其中将固定剂量直接施用到手术创建的切除腔（SCRC）中，确认这种方法可改善具有可接受毒性的恶性神经胶质瘤患者的生存率。这些试验伴随剂量测定研究的关键观察结果是，结果表明，结果与SCRC周边的剂量最紧密相关。具体而言，对SCRC周长少于44 Gy的患者的毒性最小，但肿瘤复发率较高。相反，那些接受超过44个GY的患者的肿瘤复发率较低，但有症状的放射性疾病率较高。我们的假设是，我们对131I -81C6进行的II期研究向2 cm SCRC周边提供了44 Gy，将改善新诊断为恶性神经胶质瘤的患者的存活率，同时最大程度地减少对正常CNS组织的辐射损伤。该提案的具体目的是：特定目的1。定义131i标记的抗甲环蛋白单克隆抗体的功效81C6，以剂量给予，以将44 Gy送给新诊断出恶性肿瘤的患者的切除腔的2 cm外周长；具体目的2。要进一步定义这种方法的毒性和特定目的3.确定这种疗法对生活质量的影响。